Current therapies in rheumatoid arthritis: A Latin American perspective

array:24 ["pii" => "S2173574313000130" "issn" => "21735743" "doi" => "10.1016/j.reumae.2013.01.007" "estado" => "S300" "fechaPublicacion" => "2013-03-01" "aid" => "507" "copyright" => "Elsevier España, S.L.. All rights reserved" "copyrightAnyo" => "2012" "documento" => "article" "crossmark" => 0 "subdocumento" => "ssu" "cita" => "Reumatol Clin. 2013;9:106-12" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 4287 "formatos" => array:3 [ "EPUB" => 48 "HTML" => 3212 "PDF" => 1027 ] ] "Traduccion" => array:1 [ "en" => array:19 [ "pii" => "S1699258X12002525" "issn" => "1699258X" "doi" => "10.1016/j.reuma.2012.09.001" "estado" => "S300" "fechaPublicacion" => "2013-03-01" "aid" => "507" "copyright" => "Elsevier España, S.L." "documento" => "article" "crossmark" => 0 "subdocumento" => "ssu" "cita" => "Reumatol Clin. 2013;9:106-12" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 13860 "formatos" => array:3 [ "EPUB" => 141 "HTML" => 11236 "PDF" => 2483 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Review article" "titulo" => "Current therapies in rheumatoid arthritis: A Latin American perspective" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "106" "paginaFinal" => "112" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Las terapias actuales en la artritis reumatoide: una perspectiva latinoamericana" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3514 "Ancho" => 3045 "Tamanyo" => 722591 ] ] "descripcion" => array:1 [ "en" => "RA treatment. TF (maximum doses after 8–12 weeks; DAS28>3.2).<a class="elsevierStyleCrossRef" href="#bib0095">19</a>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Rubén Burgos-Vargas, Luis Jose Catoggio, Claudio Galarza-Maldonado, Kasmir Ostojich, Mario H. Cardiel" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Rubén" "apellidos" => "Burgos-Vargas" ] 1 => array:2 [ "nombre" => "Luis Jose" "apellidos" => "Catoggio" ] 2 => array:2 [ "nombre" => "Claudio" "apellidos" => "Galarza-Maldonado" ] 3 => array:2 [ "nombre" => "Kasmir" "apellidos" => "Ostojich" ] 4 => array:2 [ "nombre" => "Mario H." "apellidos" => "Cardiel" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173574313000130" "doi" => "10.1016/j.reumae.2013.01.007" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574313000130?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X12002525?idApp=UINPBA00004M" "url" => "/1699258X/0000000900000002/v1_201305061535/S1699258X12002525/v1_201305061535/en/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2173574313000269" "issn" => "21735743" "doi" => "10.1016/j.reumae.2012.11.003" "estado" => "S300" "fechaPublicacion" => "2013-03-01" "aid" => "514" "copyright" => "Elsevier España, S.L." "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Reumatol Clin. 2013;9:113-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 5117 "formatos" => array:3 [ "EPUB" => 56 "HTML" => 4115 "PDF" => 946 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Special Article" "titulo" => "Biosimilar Drugs in Mexico: Position of the Mexican College of Rheumatology, 2012" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "113" "paginaFinal" => "116" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Medicamentos biocomparables en México: la postura del Colegio Mexicano de Reumatología, 2012" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Rolando Espinosa Morales, Alejandro Díaz Borjón, Leonor Adriana Barile Fabris, Jorge Antonio Esquivel Valerio, Gabriel Medrano Ramírez, César Alejandro Arce Salinas, Eduardo Rubén Barreira Mercado, Mario Humberto Cardiel Ríos, Efraín Díaz Jouanen, Francisco Javier Flores Murrieta, Antonio Fraga Mouret, Mario Alberto Garza Elizondo, Miguel Luján Estrada, Francisco José Muñoz Barradas, Juan Osvaldo Talavera Piña, Olga Lidia Vera Lastra" "autores" => array:16 [ 0 => array:2 [ "nombre" => "Rolando" "apellidos" => "Espinosa Morales" ] 1 => array:2 [ "nombre" => "Alejandro" "apellidos" => "Díaz Borjón" ] 2 => array:2 [ "nombre" => "Leonor Adriana" "apellidos" => "Barile Fabris" ] 3 => array:2 [ "nombre" => "Jorge Antonio" "apellidos" => "Esquivel Valerio" ] 4 => array:2 [ "nombre" => "Gabriel" "apellidos" => "Medrano Ramírez" ] 5 => array:2 [ "nombre" => "César Alejandro" "apellidos" => "Arce Salinas" ] 6 => array:2 [ "nombre" => "Eduardo Rubén" "apellidos" => "Barreira Mercado" ] 7 => array:2 [ "nombre" => "Mario Humberto" "apellidos" => "Cardiel Ríos" ] 8 => array:2 [ "nombre" => "Efraín" "apellidos" => "Díaz Jouanen" ] 9 => array:2 [ "nombre" => "Francisco Javier" "apellidos" => "Flores Murrieta" ] 10 => array:2 [ "nombre" => "Antonio" "apellidos" => "Fraga Mouret" ] 11 => array:2 [ "nombre" => "Mario Alberto" "apellidos" => "Garza Elizondo" ] 12 => array:2 [ "nombre" => "Miguel" "apellidos" => "Luján Estrada" ] 13 => array:2 [ "nombre" => "Francisco José" "apellidos" => "Muñoz Barradas" ] 14 => array:2 [ "nombre" => "Juan Osvaldo" "apellidos" => "Talavera Piña" ] 15 => array:2 [ "nombre" => "Olga Lidia" "apellidos" => "Vera Lastra" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1699258X12002689" "doi" => "10.1016/j.reuma.2012.11.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X12002689?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574313000269?idApp=UINPBA00004M" "url" => "/21735743/0000000900000002/v1_201304200246/S2173574313000269/v1_201304200246/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2173574312001475" "issn" => "21735743" "doi" => "10.1016/j.reumae.2012.04.012" "estado" => "S300" "fechaPublicacion" => "2013-03-01" "aid" => "457" "copyright" => "Elsevier España, S.L." "documento" => "article" "crossmark" => 0 "subdocumento" => "ssu" "cita" => "Reumatol Clin. 2013;9:101-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 4093 "formatos" => array:3 [ "EPUB" => 61 "HTML" => 3320 "PDF" => 712 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Review Article" "titulo" => "Treat to Target Strategy in Rheumatoid Arthritis: Real Benefits" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "101" "paginaFinal" => "105" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Estrategia «treat to target» en la artritis reumatoide: beneficios reales" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Mario H. Cardiel" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Mario H." "apellidos" => "Cardiel" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1699258X12001301" "doi" => "10.1016/j.reuma.2012.04.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X12001301?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574312001475?idApp=UINPBA00004M" "url" => "/21735743/0000000900000002/v1_201304200246/S2173574312001475/v1_201304200246/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "Review article" "titulo" => "Current therapies in rheumatoid arthritis: A Latin American perspective" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "106" "paginaFinal" => "112" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Rubén Burgos-Vargas, Luis Jose Catoggio, Claudio Galarza-Maldonado, Kasmir Ostojich, Mario H. Cardiel" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Rubén" "apellidos" => "Burgos-Vargas" "email" => array:1 [ 0 => "r.burgos.vargas@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Luis Jose" "apellidos" => "Catoggio" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Claudio" "apellidos" => "Galarza-Maldonado" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Kasmir" "apellidos" => "Ostojich" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "Mario H." "apellidos" => "Cardiel" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Department of Rheumatology, Hospital General de Mexico, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Rheumatology Section, Medical Services, Hospital Italiano de Buenos Aires, Instituto Universitario Escuela de Medicina Hospital Italiano de Buenos Aires and Fundacion Dr. Pedro M. Catoggio para el Progreso de la Reumatologia, Buenos Aires, Argentina" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Unit of Rheumatic and Autoimmune Diseases UNERA, Lupus Center, Mont Sinai Hospital, Cuenca, Ecuador" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Senior Regional Medical Director, Pfizer Inc., Latin America, Mexico City, Mexico" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Research Unit, Hospital General Dr. Miguel Silva, Morelia, Michoacan, Mexico" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Las terapias actuales en la artritis reumatoide: una perspectiva latinoamericana" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3411 "Ancho" => 3045 "Tamanyo" => 692829 ] ] "descripcion" => array:1 [ "en" => "RA treatment. TF (maximum doses after 8–12 weeks; DAS28>3.2).<a class="elsevierStyleCrossRef" href="#bib0095">19</a>" ] ] ] "textoCompleto" => "IntroductionRheumatoid arthritis (RA) is clinically recognized as an inflammatory process that mainly affects the synovium of joints and tendons and often some extra-articular sites. Classically, the criteria for RA classification relied on the presence of signs and symptoms indicative of inflammatory activity which typically implied irreversible structural damage when present. This situation led to the addition of a new set of classification criteria endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) for the diagnosis of RA. The aims of such an initiative were to establish a set of rules to be applied to newly presenting patients with undifferentiated synovitis that would: (1) identify the subset at high risk of chronicity and erosive damage; (2) be used as a basis for initiating disease-modifying therapy; and (3) not exclude the capture of patients later in the disease course.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> In this way, early and appropriate disease-modifying treatment, aimed to reduce the risk of joint destruction, could be initiated.At first glance, early recognition of patients at risk of erosive RA and swift initiation of treatment should be achievable worldwide. Programs for early diagnosis of patients with undifferentiated arthritis at risk of RA can be instituted at the level of primary health clinics. Once diagnosed, at-risk patients can be treated with disease-modifying antirheumatic drugs (DMARDs) with or without biologic agents with the goal of achieving disease remission and avoiding structural damage. While these goals and strategies have already been launched in the European Union, Canada, and the United States, less progress has been achieved in Latin America. The success of these programs across the world depends on who covers the cost of health care. In Europe and Canada, where health care costs are covered by the state, coverage for RA, for example, depends on the percentage of the health-care budget allocated to rheumatic diseases. In Latin America, the funding situation differs among countries where many state health budgets are limited. Consequently only a fraction of the population has full health coverage, and many patients pay for expenses out of pocket to cover the cost of medical care and insurance. In this sense, the implementation of programs for early detection and treatment of RA might be less successful than in developed countries.The objectives of this paper are to examine existing treatment practices for RA and discuss the socioeconomic impact of RA from a Latin American perspective.EpidemiologyThere are few reports on the prevalence of RA in Latin America. Recent reports from Argentina show prevalence rates ranging between 0.2% in Tucuman province and the city of Buenos Aires and 0.94% in Lujan province in the province of Buenos Aires, Argentina.<a class="elsevierStyleCrossRefs" href="#bib0010">2–4</a> The recent epidemiological study on musculoskeletal pain involving 25,587 subjects conducted in five regions in Mexico (Chihuahua, Nuevo Leon, Sinaloa, Yucatan, and Mexico City) showed an overall RA prevalence of 1.6% (95% CI: 1.4–1.8)<a class="elsevierStyleCrossRef" href="#bib0025">5</a>; the prevalence in females was 2.0%, while that of males reached 0.8%. The prevalence of RA varied across country regions, specifically, from 0.7 in the Nuevo León state to 2.8% in Yucatán state. One previous study in México City showed a prevalence of 0.4%.<a class="elsevierStyleCrossRef" href="#bib0030">6</a>Latin America, with a heterogeneous population estimated at 577 million people, has young adults as the dominant demographic group. RA can start at an early age, as shown by a study comparing patients from Mexico with those from Canada. Mexican patients developed RA almost 12 years earlier than Canadians (95% CI: 9–15 years, P<.0001).<a class="elsevierStyleCrossRef" href="#bib0035">7</a> Almost half of Mexicans, compared with a quarter of Canadians, had their first swollen joint before the age of 36 years. About 4% of Mexicans and 35.5% of Canadians had onset of RA after the age of 55 years (P<.001). RA mainly affects women in their productive years of life.Socioeconomic impact of rheumatoid arthritisLatin America, like many other developing regions of the world, has undergone an epidemiological shift from acute to chronic disease as the major contributor to morbidity and mortality, while still confronting problems such as poverty and malnutrition.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> Consequently, these changes impact the allocation of health-care resources from acute diseases, such as infections, to chronic diseases such as RA.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> RA is a chronic disease with substantial burden to the patient (reduced function and lower quality of life), society (loss of productivity through sick leave or permanent work disability [PWD]), and on health-care resources. <a class="elsevierStyleCrossRef" href="#bib0050">10</a> In Mexico, for example, the annual cost of RA and ankylosing spondylitis corresponded to $2900 and $2800 USD, respectively, when direct costs and out-of-the-pocket expenses are considered.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> More recently, we estimated the annual cost of RA per patient in $5534 USD dollars including indirect costs.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> The reported prevalence of PWD in the country due to RA is 11.7% and this represents a significant cost to Mexican society and to the Instituto Mexicano del Seguro Social (IMSS), which is the main health-care provider for salaried workers in the country.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> A lower education level, treatment delay, and positive rheumatoid factor (RF) were shown to increase the risk for PWD in Mexicans with RA.Health care is typically fragmentary in Latin America. In some countries, the state provides for the majority of health care while in others, individuals pay all or some of the medical expenses. Reimbursement is very limited and is only available in some countries. Access programs are available in some countries where the government usually provides the drug. The coverage varies from 60 to 100% of the population and not all biologics are available. Mexico has the social security or institutional programs of Petróleos Mexicanos (PEMEX) and Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Brazil has Sistema Unico de Saude, Venezuela has the Instituto Venezolano de los Seguros Sociales which offers almost 100% coverage, Colombia has the Entidades Promotoras de Salud, Ecuador has partial and very limited coverage through social security, and Peru has very limited coverage by social security or by other government institutions. Argentina has different governmental and private programs offering different degrees of coverage. In Chile, the public health-care system accounts for 80% of the population while the remaining 20% is covered by private health care.Early treatment of RA translates into substantial reduction in the cost to society.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> In light of this, early disease clinics are being established in some countries, including Argentina, Colombia, Brazil, Mexico, and Peru. A Colombian study showed that the time to referral from primary to tertiary care for RA patients improved from 1998 to 2002 with the introduction of early disease clinics; 54% of patients were referred within 3–6 months of diagnosis by 2002 and DMARDs were shown to be the leading first-line and second-line treatment options, with biologics accounting for 16% of second-line prescriptions in 2002.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> In Argentina, the Consorcio Argentino de Artritis Temprana database was established that specifically focuses on patients with early RA (ERA) to provide further data on detection and appropriate follow-up. Preliminary results showed a frank reduction in disease duration at referral in less than two years.<a class="elsevierStyleCrossRef" href="#bib0080">16</a>Barriers identified in the management of RA include inadequate health-care access and referral delays due to the lack of training of general practitioners in musculoskeletal problems, a shortage and inadequate distribution of rheumatologists in some countries, and limited access to appropriate therapy. There is also a lack of patient databases or registries for rheumatic patients in most of the Latin American countries. Additional factors contributing to poor patient prognosis include low socioeconomic status, disease related factors (e.g., severity, joint damage, comorbidities), and cost of treatment. In one study, it was reported that 15% of the family income goes to RA-related expenses and this represents 26.1% of the total annual cost per RA patient.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> In a study of 262 patients with RA in Mexico, the RA annual cost reported was USD 5534.80 per patient; 65% were direct costs (physician consultations, hospitalization, medication, and alternative therapies as well as laboratory and auxiliary tests, transportation and meals related to medical care) and 35% were indirect costs (work disability, home care, and loss of income at home),<a class="elsevierStyleCrossRef" href="#bib0060">12</a> which are similar in distribution to what has been reported in Europe.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> RA out of pocket costs caused catastrophic expenses in 46.9% of households which were associated with the type of health-care coverage (OR=2.7, 95% CI: 1.6–4.7) and disease duration (OR=1.024, 95% CI: 1.002–1.046).<a class="elsevierStyleCrossRef" href="#bib0060">12</a> Impoverishment, measured by the household inability to cover the basic food basket threshold in Mexico, occurred in 66.8% of households and was associated with catastrophic expenses (OR=3.6, 95% CI: 1.04–14.1), high health assessment questionnaire (HAQ) scores and low socioeconomic levels.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> An analysis utilizing the Quantitative Standard Monitoring of Patients with RA database cohort of 6004 patients from 25 countries evaluated the disparities of RA disease activity with gross domestic product (GDP) of a country. It found the burden of RA was substantially greater in low GDP than in high GDP countries.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> In Latin America (which has a significantly lower GDP than Europe, the United States, or Canada), the cost of biologics in general is very similar to countries with higher GDP, further impairing access to these medications.Latin American clinical criteria for the use and selection of biologics and treatment strategiesIn 2006, the Latin American Rheumatology Associations of the Pan-American League of Associations for Rheumatology (PANLAR) and the Grupo Latino Americano de Estudio de Artritis Reumatoide (GLADAR) issued the first Latin American position paper on the pharmacological treatment of RA that advocated for early aggressive therapy for RA patients.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> Efforts were focused on the issues facing the region with regards to the availability of appropriate treatment for RA and the development of treatment guidelines (shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) that can be used for clinical practice.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Subsequently, PANLAR and GLADAR issued a consensus position paper on the management of patients with RA in Latin America in 2009,<a class="elsevierStyleCrossRef" href="#bib0100">20</a> establishing the following criteria for using biologic agents in RA patients who were unresponsive to DMARDs:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•Patients having the diagnosis of RA according to ACR criteria.</li><li class="elsevierStyleListItem" id="lsti0010">•Active disease measured by a disease activity scale such as disease activity score in 28 joints (DAS28) ≥3.2 and after at least 3 months on conventional treatment with DMARDS.</li><li class="elsevierStyleListItem" id="lsti0015">•Patients should have used two DMARDs, one being methotrexate (MTX) in adequate doses, unless there were significant adverse effects.</li><li class="elsevierStyleListItem" id="lsti0020">•Adequate doses of MTX should have been up to 25mg weekly via oral, intramuscular, or subcutaneous (SC), and leflunomide 20mg per day; with the exception of patients presenting adverse events (AEs) limiting the use of these therapies.</li><li class="elsevierStyleListItem" id="lsti0025">•Patients should be in functional ACR status I, II, or III.</li></ul>GLADAR also developed evidence-based guidelines specific for the use of rituximab in the treatment of RA in Latin America.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> GLADAR recommends rituximab in patients with active (DAS28>3.2) RF-positive RA who had inadequate response or intolerance to an adequate course as previously defined with tumor necrosis factor (TNF) inhibitors. Rituximab can also be used in patients who have inadequate response or intolerance to more than one conventional DMARD and cannot receive TNF inhibitors (due to contraindications or unavailability). Based on lack of strong evidence, rituximab cannot be recommended to RF-negative RA patients; GLADAR, however, recommends that RF-negative patients be considered for treatment if they meet the conventional treatment failure criteria.<a class="elsevierStyleCrossRef" href="#bib0105">21</a>Some countries have developed their own treatment guidelines for RA based on the PANLAR/GLADAR guidelines but adapted to their own situations. In Argentina, clinical practice guidelines for RA were developed by the Argentine Society of Rheumatology in 2003 and were updated in 2008. It has since undergone annual updates to keep up with the continuing advances in the understanding of the pathogenesis, evolution, and treatment of RA to include new diagnostic technologies and new drugs.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> In Brazil, the Brazilian Society of Rheumatology (SBR) published the “Brazilian Consensus for the Diagnosis and Treatment of RA” in the 2004 Brazilian Journal of Rheumatology. The consensus was updated in 2007 to include grades of recommendations and strength of evidence based on the previous work of SBR, the experiences of rheumatologists, and literature review.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> In Chile, the Ministry of Health issued the RA Clinical Guide Series in 2007 which included flow diagrams in the management of patients with RA and early diagnosis, referral, and treatment among its key recommendations.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> In Colombia, the Colombian Association of Rheumatology published the first edition of the “Guidelines for the Treatment of RA” in 2002. The guidelines were intended to minimize clinical variability of managing RA and to facilitate the clinical evaluation, financial, and legal processes, as well as streamlining cost associated with RA treatment.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> In Costa Rica, the Costa Rican Association of Rheumatology and the College of Physicians and Surgeons developed the “Guidelines for the Management of RA” 2010 Consensus, which considered the severity of RA as a disease that can eventually be modified and the need for close monitoring of the patient preferably by a rheumatologist.<a class="elsevierStyleCrossRef" href="#bib0130">26</a> In Mexico, the Mexican College of Rheumatology issued guidelines and recommendations in 2006<a class="elsevierStyleCrossRef" href="#bib0135">27</a> and the IMSS published guidelines in 2010 for the treatment of RA recommending biologics.<a class="elsevierStyleCrossRef" href="#bib0140">28</a>Current clinical practiceLatin American rheumatologists are aware of the importance of early detection and diagnosis of RA and the short- and long-term efficacy of DMARD or DMARD plus biologic agents. However, the implementation of early detection clinics and early treatment can be difficult because of inadequate financial resources needed to fund such programs. One of several strategies to minimize cost of early detection and treatment would be combining the presumptive diagnosis of RA by a rheumatologist with the presence of anti-cyclic citrullinated peptides (CCP) antibodies. Such combination was shown to be highly specific for diagnosing RA in patients with very early arthritis. The sensitivity and specificity of prediction by a rheumatologist were 94% and 74%, respectively; for anti-CCP antibodies, they were 56% and 96%, respectively. Combining the two variables resulted in a specificity of 100% and a sensitivity of 53%, and a positive predictive value of 98%.<a class="elsevierStyleCrossRef" href="#bib0145">29</a>While debate exists about when is the best time to start treatment (within 3, 6, or 12 months), the aim is to treat as early as possible, according to patient needs. Treat-to-target with the objective of disease remission and/or low disease activity (LDA) score is practiced in some clinics in the region; close monitoring of AEs and consideration of patient comorbidities are necessary. It is important to consider each patient individually and to adopt practical strategies to meet their needs. Tight control strategies versus “routine” practice has been assessed in studies, suggesting that intensive patient management and treating to target reduce disease activity and radiographic progression compared with routine or symptomatic outpatient care.<a class="elsevierStyleCrossRefs" href="#bib0150">30,31</a>Very early rheumatoid arthritis/early rheumatoid arthritisExpert consensus defined very early RA as the RA occurring between 3 and 4–6 months and early RA (ERA at one year). Early diagnosis of RA can be difficult because patients who have very recent onset arthritis (≤12 weeks of evolution) may have been diagnosed with other diseases, including self-limited arthritis. Hence, the sensitivity and specificity of classification criteria for RA established by the ACR are not effective for this particular group of RA patients.<a class="elsevierStyleCrossRef" href="#bib0145">29</a> Further, 80.4% of early inflammatory arthritis was shown to progress to persistent arthritis.<a class="elsevierStyleCrossRef" href="#bib0160">32</a>For the management of early arthritis or ERA, the EULAR task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT) developed a set of 12 recommendations based on evidence in the literature and expert consensus; detailed descriptions are published elsewhere.<a class="elsevierStyleCrossRef" href="#bib0165">33</a>Biologic registriesEducating the physicians, patients, community, and policy makers is important in RA treatment. Equally important is maintaining accurate records on all aspects of prescribed biologics, particularly on AEs and treatment duration. The establishment of local disease registries addresses this need and provides a better understanding of rheumatic disease and its treatment in the region. To address safety concerns, the Pan-American Registry of AEs of Biological Therapies in Rheumatic Diseases was established in 2007 as a collaboration between PANLAR and the Sociedad Española de Reumatología (SER). It is considered an important resource to monitor biologic-related AEs in the Latin American region. This registry includes data on 1481 rheumatic-disease patients available from 1998 to 2009.<a class="elsevierStyleCrossRef" href="#bib0170">34</a> Some country-specific biologics registries include BIOBADASAR (Argentina), established in 2010, BIOBADABRASIL (Brazil) and BIOBADAMEX (Mexico), both established in 2008. The implementation and maintenance of these registries require substantial funding and monitoring. Although initially established by national societies of rheumatology, registries also receive financial support from pharmaceutical manufacturers (e.g., BIOBADABRASIL) and essential academic support from SER.Prescribing biologics in Latin AmericaRheumatologists in Latin America have clinical experience in treating RA patients who have access with TNF inhibitors and other biologics. Patients were treated with biologics after experiencing MTX failure, multiple DMARD failures and experiencing early, aggressive RA who are both MTX and biologic naïve following regional guidelines. A list of the biologic agents for the treatment of RA in Latin America is presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Future therapiesKinase inhibitors currently under investigation for RA include tofacitinib (CP-690,550) and fostamatinib (R788).<a class="elsevierStyleCrossRefs" href="#bib0205">41,42</a> Tofacitinib is a janus kinase inhibitor shown in phase 3 trials to be effective in patients with moderate to severe active RA; ACR50 response rates at month 6 of up to 37% in tofacitinib versus 12% in placebo patients who had inadequate response to MTX were achieved with improvement in pain and physical function compared with placebo.<a class="elsevierStyleCrossRef" href="#bib0215">43</a> Fostamatinib (R788) is a spleen tyrosine kinase inhibitor that was evaluated in a 6-month, double-blind, placebo controlled trial in patients with active RA and on long-term MTX therapy. Results showed ACR50 response rates of up to 43% in fostamatinib patients versus 19% in placebo patients.<a class="elsevierStyleCrossRef" href="#bib0220">44</a> Other biologic agents for future consideration in Latin America include the monoclonal antibodies golimumab and certolizumab pegol. Golimumab was shown in a randomized, double-blind, placebo-controlled phase 3 trial to reduce the signs and symptoms of RA in patients who received prior TNF-inhibitor therapy; ACR20 was achieved at week 14 by 35% and 38% of patients on 50mg and 100mg, respectively.<a class="elsevierStyleCrossRef" href="#bib0225">45</a> Certolizumab pegol plus MTX was shown in a randomized, double-blind, placebo-controlled phase 3 trial to be more efficacious than placebo in patients with active RA who achieved an ACR20 response.<a class="elsevierStyleCrossRef" href="#bib0230">46</a> Certolizumab pegol is expected to be approved in Chile and Mexico in 2012; its approval is pending in Argentina and Ecuador.BiosimilarsBiosimilars are biopharmaceuticals that may be similar to the innovator product and enter the market when the patent of the original biologic product expires (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Although the development of biosimilar or “follow on” proteins is expensive, an estimated 30% of costs can be saved on current patented biologics.<a class="elsevierStyleCrossRef" href="#bib0235">47</a> While biosimilars are comparable to their biologic counterparts in safety and efficacy,<a class="elsevierStyleCrossRef" href="#bib0240">48</a> they are not identical due to the manufacturing process, which is more complex than that of generic small molecule products.<a class="elsevierStyleCrossRef" href="#bib0235">47</a> Minor changes present in biosimilars could be immunogenic, thus possibly interfering with efficacy and safety. As such, efficacy and safety data of biologics should not be extrapolated to biosimilars; neither should biologics and biosimilars be considered interchangeable unless strict biochemical and clinical studies with long term evaluation are performed.<a class="elsevierStyleCrossRef" href="#bib0245">49</a> Furthermore long term safety of either agent cannot be adequately assessed if patients change a biologic for a biosimilar or vice versa. Pharmacovigilance is particularly important with the use of any biologic.<a class="elsevierStyleCrossRef" href="#bib0250">50</a> Biosimilars should be considered interchangeable with the original product only after sufficient clinical data and marketplace experience have been accrued. Approval of biosimilars should be tightly regulated and require direct head-to-head toxicological, nonclinical, and clinical data in comparison to the reference biologic. Regulatory aspects are particularly important, and clinicians should be included in the review process.<a class="elsevierStyleCrossRef" href="#bib0255">51</a><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Colombia in Latin America had approved the etanercept biosimilar, Etanar, for the treatment of inflammatory diseases, although regulations for the approval of biosimilars are still under development. In 2006, Etanar was imported to Colombia from China, approved for the treatment of RA, and was made available through the social security system. In Colombia, the efficacy and safety of Etanar (25mg SC twice weekly) were shown in a multicenter, observational before-after study involving 110 patients with active RA despite treatment with DMARDs who were followed for 20 weeks.<a class="elsevierStyleCrossRef" href="#bib0260">52</a> DAS28 decreased from 5.76±0.81 to 3.48±1.12 (P<.001) and HAQ decreased from 2.5±1.1 to 1.1±0.9 (P<.001). Side effects were reported in 10% of patients. Reasons for discontinuation were lack of efficacy, heart failure, nausea, dizziness, pneumonia, and asthma.<a class="elsevierStyleCrossRef" href="#bib0260">52</a>Recently Reditux, a rituximab biosimilar produced by Dr Reddy's Laboratories (India) has become available in some countries of Latin America including Peru, Ecuador, Chile, Bolivia, and Venezuela.<a class="elsevierStyleCrossRef" href="#bib0265">53</a>ConclusionsIn summary, it is clear that the policy of most Latin American academic rheumatologists is to diagnose as early as possible, treat early with conventional DMARDs alone or in combination, aim at remission or LDA (treat-to-target) and then add biologics if disease control is not adequate.Management of RA has a defined treatment pattern that is adjusted based on patients’ response to therapy. Typically, MTX is the initial therapy and, in the case of inadequate response or adverse reaction, is followed by adding in combinations of other DMARDs. This is then followed by biologics, which are either cycled, in the case of TNF-α inhibitors, or changed based on their mechanism of action. The concept of early treatment and treat-to-target are well recognized in academic rheumatology but still need to be established in general practitioners’ minds and payers.Challenges for Latin American countries, as in other parts of the world, in the treatment of RA include making RA a public health priority, knowing its socioeconomic impact in terms of its high cost and burden on the health-care system, and increasing access to prompt diagnosis, treatment by rheumatologists, and availability of effective low cost medications. Other issues of concern include regularly updating guidelines, developing treatment algorithms based on local needs and resources, establishing routine epidemiological surveillance, and educating the people, patients, and health-care providers.Ethical disclosuresProtection of human and animal subjectsThe authors declare that no experiments were performed on humans or animals for this investigation.Confidentiality of dataThe authors declare that no patient data appears in this article.Right to privacy and informed consentThe authors declare that no patient data appears in this article.Conflict of interestRubén Burgos Vargas has participated on advisory boards for Abbott, BMS, Jannsen, Pfizer, and Roche, and as a speaker for Abbott, BMS, Jannsen, Pfizer, and Roche.Kasmir Ostojich was a Regional Medical Director of Medical Affairs for Pfizer Inc, Inflammation during the development of this manuscript.Mario H. Cardiel is a clinical researcher who has conducted clinical trials for Pfizer, Roche, Bristol Myers Squibb, La Jolla Pharmaceutical, Anthera, Astra Zeneca, Chelsea. He has been a speaker and consultant for Pfizer, Bristol Myers Squibb, Abbott and Merck." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:2 [ "identificador" => "xres90923" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec78147" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres90922" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec78146" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Epidemiology" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Socioeconomic impact of rheumatoid arthritis" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Latin American clinical criteria for the use and selection of biologics and treatment strategies" ] 8 => array:3 [ "identificador" => "sec0025" "titulo" => "Current clinical practice" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Very early rheumatoid arthritis/early rheumatoid arthritis" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Biologic registries" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Prescribing biologics in Latin America" ] 3 => array:2 [ "identificador" => "sec0045" "titulo" => "Future therapies" ] 4 => array:2 [ "identificador" => "sec0050" "titulo" => "Biosimilars" ] ] ] 9 => array:2 [ "identificador" => "sec0055" "titulo" => "Conclusions" ] 10 => array:3 [ "identificador" => "sec0060" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0070" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0075" "titulo" => "Right to privacy and informed consent" ] ] ] 11 => array:2 [ "identificador" => "sec0080" "titulo" => "Conflict of interest" ] 12 => array:2 [ "identificador" => "xack34611" "titulo" => "Acknowledgments" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-04-23" "fechaAceptado" => "2012-09-08" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec78147" "palabras" => array:5 [ 0 => "Rheumatoid arthritis" 1 => "Latin America" 2 => "Socioeconomic factors" 3 => "Practice guidelines" 4 => "Biologic therapy" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec78146" "palabras" => array:5 [ 0 => "Artritis reumatoide" 1 => "América Latina" 2 => "Factores socioeconómicos" 3 => "Guías de práctica clínica" 4 => "Terapia biológica" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Rheumatoid arthritis (RA) is a systemic inflammatory disease affecting the synovium of joints, tendons, and some extra-articular sites. RA prevalence in Latin America ranges from 0.4 to 1.6%. Early treatment of RA translates into a substantial reduction in the cost to society. In light of this, early disease clinics are being established in some countries. Barriers to RA management, such as delay in referral to rheumatologists and limited access to therapy, have been identified. Evidence-based treatment guidelines have been adapted by countries according to their own situations. The need for keeping accurate records of biologics prescribed has been addressed by biologic registries, thereby contributing toward a better understanding of rheumatic diseases and their treatment. Current biologics include the tumor necrosis factor (TNF)-α inhibitors (etanercept, infliximab, and adalimumab), B-cell depletion agent (rituximab), interleukin-6 receptor blocker (tocilizumab), and T-cell co-stimulatory blocker (abatacept). Future therapies include kinase inhibitors (tofacitinib and fostamatinib), alternative TNF-α inhibitors (golimumab and certolizumab), and biosimilars." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La artritis reumatoide (AR) es una enfermedad sistémica e inflamatoria que afecta la membrana sinovial de las articulaciones, los tendones y algunos sitios extra-articulares. La prevalencia de la AR en Latinoamérica se encuentra entre 0.4–1.6%. El tratamiento precoz de la enfermedad se traduce en una reducción del costo para la sociedad. En vista de esto, se han establecido clínicas de AR temprana en varios países de la región. Se han identificado barreras para el tratamiento de la AR como lo son el retraso en la referencia al reumatólogo y limitaciones en el acceso al tratamiento. Varios países han desarrollado y adaptado guías para el tratamiento basadas en la evidencia y en sus propias realidades. La necesidad de tener registros detallados de las prescripciones de biológicos ha sido abordada con registros de biológicos lo que llevará a un mejor entendimiento de las enfermedades reumáticas y su tratamiento. Los biológicos disponibles en la actualidad son los inhibidores del factor de necrosis tumoral (TNF)-α (etanercept, infliximab y adalimumab), un agente depletor de células B (rituximab), un bloqueador del receptor de interleucina-6 (tocilizumab) y un bloqueador de la co-estimulación de células T (abatacept). En el futuro se incluirán los inhibidores de cinasas (tofacitinib y fostamatinib) e inhibidores del TNF-α alternativos (golimumab y certolizumab) y biosimilares." ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3411 "Ancho" => 3045 "Tamanyo" => 692829 ] ] "descripcion" => array:1 [ "en" => "RA treatment. TF (maximum doses after 8–12 weeks; DAS28>3.2).<a class="elsevierStyleCrossRef" href="#bib0095">19</a>" ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "RA, rheumatoid arthritis; TNF, tumor necrosis factor." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Mechanism of action \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Biologic agents \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TNF-α inhibitors \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Etanercept,<a class="elsevierStyleCrossRef" href="#bib0175">35</a> infliximab,<a class="elsevierStyleCrossRef" href="#bib0180">36</a> adalimumab<a class="elsevierStyleCrossRef" href="#bib0185">37</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">B-cell depletion agent \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rituximab<a class="elsevierStyleCrossRef" href="#bib0190">38</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T-cell co-stimulatory blockers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Abatacept<a class="elsevierStyleCrossRef" href="#bib0195">39</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cytokine inhibitor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tocilizumab<a class="elsevierStyleCrossRef" href="#bib0200">40</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab176524.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Biologic agents for the treatment of RA in Latin America." ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "RA, rheumatoid arthritis." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Biosimilar/company \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Current status \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Original product (biologic) \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TL011/Teva Pharmaceutical Industries Ltd.<a class="elsevierStyleCrossRef" href="#bib0270">54</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Phase 1 and 2 clinical trials \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rituxan (rituximab) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reditux/Dr Reddy's Laboratories<a class="elsevierStyleCrossRef" href="#bib0265">53</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Launched in 2007 and is marketed in India and several other countries \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rituxan (rituximab) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yisaipu/Shanghai CP Guojian Pharmaceuticals Co., Ltd.<a class="elsevierStyleCrossRef" href="#bib0275">55</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">In use in China since 2005 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Enbrel (etanercept) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Etanar/Lafrancol<a class="elsevierStyleCrossRef" href="#bib0260">52</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">In use in Colombia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Enbrel (etanercept) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PRX-106/Protalix Biotherapeutics<a class="elsevierStyleCrossRef" href="#bib0280">56</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Preclinical \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Enbrel (etanercept) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TNFcept/LG Life Sciences<a class="elsevierStyleCrossRef" href="#bib0285">57</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Phase 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Enbrel (etanercept) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TNFmab/LG Life Sciences<a class="elsevierStyleCrossRef" href="#bib0285">57</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Preclinical \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Remicade (infliximab) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab176525.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Biosimilar agents for the treatment of RA." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:57 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Aletaha" 1 => "T. Neogi" 2 => "A.J. Silman" 3 => "J. Funovits" 4 => "D.T. Felson" 5 => "C.O. Bingham IIIrd" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.27584" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2010" "volumen" => "62" "paginaInicial" => "2569" "paginaFinal" => "2581" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20872595" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of rheumatoid arthritis in Tucumán, Argentina" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Spindler" 1 => "V. Bellomio" 2 => "A. Berman" 3 => "E. Lucero" 4 => "M. Baigorria" 5 => "S. Paz" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Rheumatol" "fecha" => "2002" "volumen" => "29" "paginaInicial" => "1166" "paginaFinal" => "1170" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12064829" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Health care utilization and direct medical costs in patients with rheumatoid arthritis in a developing country" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "E.R. Soriano" 1 => "C. Castel del Cid" 2 => "F. Devoto" 3 => "P. Imamura" 4 => "L. Catoggio" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Rheumatology" "fecha" => "2005" "volumen" => "44" "paginaInicial" => "i54" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The prevalence of rheumatoid arthritis in Argentina: a capture-recapture study in a city in Buenos Aires province" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Scublinsky" 1 => "H. Venarotti" 2 => "G. Citera" 3 => "O.D. Messina" 4 => "E. Scheines" 5 => "O. Rillo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/RHU.0b013e3181f3bfdd" "Revista" => array:6 [ "tituloSerie" => "J Clin Rheumatol" "fecha" => "2010" "volumen" => "16" "paginaInicial" => "317" "paginaFinal" => "321" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20859227" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of the rheumatic diseases in Mexico. A study of 5 regions based on the COPCORD methodology" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I. Peláez-Ballestas" 1 => "L.H. Sanin" 2 => "J. Moreno-Montoya" 3 => "J. Alvarez-Nemegyei" 4 => "R. Burgos-Vargas" 5 => "M. Garza-Elizondo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3899/jrheum.100951" "Revista" => array:6 [ "tituloSerie" => "J Rheumatol Suppl" "fecha" => "2011" "volumen" => "86" "paginaInicial" => "3" "paginaFinal" => "8" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21196592" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Community based study to estimate prevalence, burden of illness and help seeking behavior in rheumatic diseases in Mexico City. A COPCORD study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.H. Cardiel" 1 => "J. Rojas-Serrano" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Exp Rheum" "fecha" => "2002" "volumen" => "20" "paginaInicial" => "617" "paginaFinal" => "662" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Latitude gradient influences the age of onset of rheumatoid arthritis patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Ramos-Remus" 1 => "G. Sierra-Jimenez" 2 => "K. Skeith" 3 => "F.J. Aceves-Avila" 4 => "A.S. Russell" 5 => "R. Offer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-007-0666-2" "Revista" => array:6 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2007" "volumen" => "26" "paginaInicial" => "1725" "paginaFinal" => "1728" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17646901" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Challenges in the management of rheumatoid arthritis in developing countries" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "G.M. Mody" 1 => "M.H. Cardiel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.berh.2008.04.003" "Revista" => array:6 [ "tituloSerie" => "Best Pract Res Clin Rheumatol" "fecha" => "2008" "volumen" => "22" "paginaInicial" => "621" "paginaFinal" => "641" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18783741" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Bloomberg School of Public Health, Johns Hopkins University. Non-communicable chronic diseases in Latin America and the Caribbean. The Healthy Caribbean Coalition Website: <a class="elsevierStyleInterRef" href="http://www.healthycaribbean.org/publications/documents/NCD-in-LAC-USAID.pdf">http://www.healthycaribbean.org/publications/documents/NCD-in-LAC-USAID.pdf</a> [accessed 13.11.11]." ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The burden of illness of rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Boonen" 1 => "J.L. Severens" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-010-1634-9" "Revista" => array:6 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2011" "volumen" => "30" "paginaInicial" => "S3" "paginaFinal" => "S8" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21359507" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Social costs of the most common inflammatory rheumatic disease in Mexico from the patient's perspective" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Mould-Quevedo" 1 => "I. Peláez-Ballestas" 2 => "J. Vásquez-Mellado" 3 => "L. Terán-Estrada" 4 => "J. Esquivel-Valerio" 5 => "L. Ventura-Ríos" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gac Med Mex" "fecha" => "2008" "volumen" => "144" "paginaInicial" => "225" "paginaFinal" => "231" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18714591" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Catastrophic expenses and rate of impoverishment as consequence of the cost of rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Álvarez-Hernández" 1 => "I. Pelaez-Ballestas" 2 => "A. Boonen" 3 => "J. Vázquez-Mellado" 4 => "A. Hernández-Garduño" 5 => "F. Carlos" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.reuma.2012.05.002" "Revista" => array:6 [ "tituloSerie" => "Reumatol Clin" "fecha" => "2012" "volumen" => "8" "paginaInicial" => "168" "paginaFinal" => "173" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22704914" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Factors associated with permanent work disability in Mexican patients with rheumatoid arthritis. A case control study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J. Morales-Romero" 1 => "L. Gonzales-Lopez" 2 => "A. Celis" 3 => "B.E. Rodriguez-Arreola" 4 => "C.E. Cabrera-Pivaral" 5 => "J.I. Gamez-Nava" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Rheumatol" "fecha" => "2006" "volumen" => "33" "paginaInicial" => "1247" "paginaFinal" => "1249" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16758509" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The costs of rheumatoid arthritis: an international long-term view" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "K.M. Pugner" 1 => "D.I. Scott" 2 => "J.W. Holmes" 3 => "K. Hieke" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Semin Arthritis Rheum" "fecha" => "2000" "volumen" => "29" "paginaInicial" => "305" "paginaFinal" => "320" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10805355" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Utilización de medicinas alternativas en la consulta reumatológica en la ciudad de Barranquilla" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Caballero-Uribe" 1 => "H. Wilches" 2 => "K. Wilches" 3 => "J. Rojas" 4 => "J. Salas Siado" 5 => "E. Forero" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Col Rheumatol" "fecha" => "2002" "volumen" => "9" "paginaInicial" => "194" "paginaFinal" => "200" ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "General characteristics of an early arthritis cohort in Argentina" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Marcos" 1 => "C. Waimann" 2 => "F. Dal Pra" 3 => "J. Hogrefe" 4 => "S. Retamozo" 5 => "F. Caeiro" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rheumatology (Oxford)" "fecha" => "2011" "volumen" => "50" "paginaInicial" => "110" "paginaFinal" => "116" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The burden of rheumatoid arthritis and access to treatment: health burden and costs" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Lundkvist" 1 => "F. Kastäng" 2 => "G. Kobelt" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10198-007-0088-8" "Revista" => array:6 [ "tituloSerie" => "Eur J Health Econ" "fecha" => "2008" "volumen" => "8" "paginaInicial" => "S49" "paginaFinal" => "S60" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18157732" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Sokka" 1 => "H. Kautiainen" 2 => "T. Pincus" 3 => "S. Toloza" 4 => "G. da Rocha Castelar Pinheiro" 5 => "J. Lazovskis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2009.109983" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2009" "volumen" => "68" "paginaInicial" => "1666" "paginaFinal" => "1672" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19643759" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "First Latin American position paper on the pharmacological treatment of rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.H. Cardiel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rheumatology (Oxford)" "fecha" => "2006" "volumen" => "45" "paginaInicial" => "ii7" "paginaFinal" => "ii22" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of patients with rheumatoid arthritis in Latin America. A Consensus position paper from Pan-American League of Associations of Rheumatology and Grupo Latino Americano de Estudio de Artritis Reumatoide" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Massardo" 1 => "M.E. Suarez-Almazor" 2 => "M.H. Cardiel" 3 => "A. Nava" 4 => "R.A. Levy" 5 => "I. Laurindo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/RHU.0b013e3181a90cd8" "Revista" => array:6 [ "tituloSerie" => "J Clin Rheumatol" "fecha" => "2009" "volumen" => "15" "paginaInicial" => "203" "paginaFinal" => "210" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19502907" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guidelines. Use of rituximab for the treatment of rheumatoid arthritis: the Latin American context" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.R. Soriano" 1 => "C. Galarza-Maldonado" 2 => "M.H. Cardiel" 3 => "B.A. Pons-Estel" 4 => "L. Massardo" 5 => "C.V. Caballero-Uribe" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/rheumatology/ken015a" "Revista" => array:6 [ "tituloSerie" => "Rheumatology" "fecha" => "2008" "volumen" => "47" "paginaInicial" => "1097" "paginaFinal" => "1099" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18463144" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Sociedad Argentina de Reumatología. Guías argentinas de práctica clínica en el tratamiento de la artritis reumatoide: Actualización. Revista Argentina de Reumatología. <a class="elsevierStyleInterRef" href="http://www.reumatologia.org.ar/userfiles/file/publicaciones/revista-reumatologia/SAR_GuiasTCZ_2011.pdf">http://www.reumatologia.org.ar/userfiles/file/publicaciones/revista-reumatologia/SAR_GuiasTCZ_2011.pdf</a> [accessed 04.04.12]." ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Update on the Brazilian consensus for the diagnosis and treatment of rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.B. Bertolo" 1 => "C.V. Brenol" 2 => "C.G. Schainberg" 3 => "F. Neubarth" 4 => "F. de Lima" 5 => "I.M. Laurindo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Bras Reumatol" "fecha" => "2007" "volumen" => "47" "paginaInicial" => "151" "paginaFinal" => "159" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guía Clínica Artritis Reumatoidea" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Ministerio de Salud" "etal" => false ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2007" "editorial" => "MINSAL" "editorialLocalizacion" => "Santiago" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "http://www.redsalud.gov.cl/archivos/guiasges/artritispdf.pdf" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guías para el tratamiento de la artritis reumatoide" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Asociación Colombiana de Reumatología" "etal" => false ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2002" "editorial" => "Exlibris Editores SA" "editorialLocalizacion" => "DC Bogota" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "http://dnn.asoreuma.org/Portals/0/Descargas/GUIA%20PARA%20EL%20TRATAMIENTO%20DE%20LA%20AR%20Parte%201.pdf" ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guías de manejo de la artritis reumatoide Concenso 2010" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Costa Rican Association of Rheumatology" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Acta Med Costarric" "fecha" => "2011" "volumen" => "53" "paginaInicial" => "19" "paginaFinal" => "25" ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Colegio Mexicano de Reumatología. Guías y recomendaciones del Colegio Mexicano de Reumatología para el uso de agentes biológicos en enfermos reumáticos" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Comité Mexicano del Consenso de Biológicos" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1699-258X(06)73026-1" "Revista" => array:6 [ "tituloSerie" => "Reumatol Clin" "fecha" => "2006" "volumen" => "2" "paginaInicial" => "78" "paginaFinal" => "89" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21794308" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Instituto Mexicano del Seguro Social. Guia de Referencia Rapida: Diagnostico y Tratamiento de Artritis Rheumatoide del Adulto. IMSS Website: <a class="elsevierStyleInterRef" href="http://www.cvsp.cucs.udg.mx/guias/TODAS/IMSS_195_08_ARTRITIS_REUMATOIDE/IMSS_195_08_GRR.pdf">http://www.cvsp.cucs.udg.mx/guias/TODAS/IMSS_195_08_ARTRITIS_REUMATOIDE/IMSS_195_08_GRR.pdf</a> [accessed 04.04.12]." ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Very recent onset arthritis: the value of initial rheumatologist and anti-cyclic citrullinated peptide antibodies in the diagnosis of rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J. Rojas-Serrano" 1 => "R. Burgos-Vargas" 2 => "L. Lino Perez" 3 => "C.G. García" 4 => "F. Moctezuma" 5 => "J. Vázquez-Mellado" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-009-1206-z" "Revista" => array:6 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2009" "volumen" => "28" "paginaInicial" => "1135" "paginaFinal" => "1139" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19504230" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Grigor" 1 => "H. Capell" 2 => "A. Stirling" 3 => "A.D. McMahon" 4 => "P. Lock" 5 => "R. Vallance" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(04)16676-2" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2004" "volumen" => "364" "paginaInicial" => "263" "paginaFinal" => "269" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15262104" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Disease activity score-driven therapy versus routine care in patients with recent onset active rheumatoid arthritis: data from the GUEPARD trial and ESPOIR cohort" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Soubrier" 1 => "C. Lukas" 2 => "J. Sibilia" 3 => "B. Fautrel" 4 => "F. Roux" 5 => "L. Gossec" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2010.137695" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2011" "volumen" => "70" "paginaInicial" => "611" "paginaFinal" => "615" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21242235" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "National Center of Rheumatic Disease (CNER). Early inflammatory polyarthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Nuñez-Sotelo" 1 => "L.A. Gutierrez-Gonzalez" 2 => "N. Gonzalez" 3 => "B. Losada" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Med Archiv" "fecha" => "2007" "volumen" => "21" "paginaInicial" => "125" "paginaFinal" => "137" ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Combe" 1 => "R. Landewe" 2 => "C. Lukas" 3 => "H.D. Bolosiu" 4 => "F. Breedveld" 5 => "M. Dougados" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2005.044354" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2007" "volumen" => "66" "paginaInicial" => "34" "paginaFinal" => "45" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16396980" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Registro Panamericano de acontecimientos adversos de terapias biológicas en enfermedades reumáticas. BIOBADASER Website: <a class="elsevierStyleInterRef" href="https://biobadaser.ser.es/biobadamerica/">https://biobadaser.ser.es/biobadamerica/</a> [accessed 07.11.11]." ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomized, double-blind, parallel treatment trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Emery" 1 => "F.C. Breedveld" 2 => "S. Hall" 3 => "P. Durez" 4 => "D.J. Chang" 5 => "D. Robertson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(08)61000-4" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2008" "volumen" => "372" "paginaInicial" => "375" "paginaFinal" => "382" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18635256" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Infliximab in active early rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.C. Breedveld" 1 => "P. Emery" 2 => "E. Keystone" 3 => "K. Patel" 4 => "D.E. Furst" 5 => "J.R. Kalden" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2004" "volumen" => "63" "paginaInicial" => "149" "paginaFinal" => "155" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14722203" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The PREMIER study: a multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.C. Breedveld" 1 => "M.H. Weisman" 2 => "A.F. Kavanaugh" 3 => "S.B. Cohen" 4 => "K. Pavelka" 5 => "R. van Vollenhoven" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.21519" "Revista" => array:7 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2006" "volumen" => "54" "paginaInicial" => "26" "paginaFinal" => "37" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16385520" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0163445312002885" "estado" => "S300" "issn" => "01634453" ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Sellam" 1 => "H. Hendel-Chavez" 2 => "S. Rouanet" 3 => "K. Abbed" 4 => "B. Combe" 5 => "X. Le Loët" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.30233" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2011" "volumen" => "63" "paginaInicial" => "933" "paginaFinal" => "938" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21225699" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition [published correction appears in N Engl J Med 2005;353:2311]" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.C. Genovese" 1 => "J.C. Becker" 2 => "M. Schiff" 3 => "M. Luggen" 4 => "Y. Sherrer" 5 => "J. Kremer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa050524" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2005" "volumen" => "353" "paginaInicial" => "1114" "paginaFinal" => "1123" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16162882" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0200" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial [published correction appears in Ann Rheum Dis 2009;68:296]" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Emery" 1 => "E. Keystone" 2 => "H.P. Tony" 3 => "A. Cantagre" 4 => "R. van Vollenhoven" 5 => "A. Sanchez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2008.092932" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2008" "volumen" => "67" "paginaInicial" => "1516" "paginaFinal" => "1523" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18625622" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0205" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Emerging therapeutics for rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "C.O. Bingham III" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Bull NYU Hosp Jt Dis" "fecha" => "2008" "volumen" => "66" "paginaInicial" => "210" "paginaFinal" => "215" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18937634" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0210" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "New and emerging therapies for the treatment of rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.G. Feely" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Open Access Rheumatol Res Rev" "fecha" => "2010" "volumen" => "2" "paginaInicial" => "35" "paginaFinal" => "43" ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0215" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tofacitinib (CP-690,550), an oral janus kinase inhibitor, or adalimumab versus placebo in patients with rheumatoid arthritis on background methotrexate: a phase 3 study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. van Vollenhoven" 1 => "R. Fleischmann" 2 => "S. Cohen" 3 => "E.B. Lee" 4 => "G. Meijide" 5 => "S. Wagner" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2011" "volumen" => "63" "paginaInicial" => "S153" ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0220" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An oral spleen tyrosine kinase (SyK) inhibitor for rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.E. Weiblatt" 1 => "A. Kavanaugh" 2 => "M.C. Genovese" 3 => "T.K. Musser" 4 => "E.B. Grossbard" 5 => "D.B. Magilavy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1000500" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2010" "volumen" => "363" "paginaInicial" => "1303" "paginaFinal" => "1312" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20879879" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0225" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor α inhibitors (GO-AFTER study): a multicenter, randomized, double-blind, placebo-controlled, phase III trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.S. Smolen" 1 => "J. Kay" 2 => "M.K. Doyle" 3 => "R. Landewé" 4 => "E.L. Matteson" 5 => "J. Wollenhaupt" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(09)60506-7" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2009" "volumen" => "374" "paginaInicial" => "210" "paginaFinal" => "221" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19560810" "web" => "Medline" ] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0230" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomized, controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Smolen" 1 => "R.B. Landewe" 2 => "P. Mease" 3 => "J. Brzezicki" 4 => "D. Mason" 5 => "K. Luijtens" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2008.101659" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2009" "volumen" => "68" "paginaInicial" => "797" "paginaFinal" => "804" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19015207" "web" => "Medline" ] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0235" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biosimilars: the debate continues" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.A. Colbert" 1 => "B.N. Cronstein" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.30505" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2011" "volumen" => "63" "paginaInicial" => "2848" "paginaFinal" => "2850" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21702015" "web" => "Medline" ] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0240" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Scientific and legal viability of follow-on protein drugs" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D.M. Dudzinski" 1 => "A.S. Kesselheim" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMhle0706973" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2008" "volumen" => "358" "paginaInicial" => "843" "paginaFinal" => "849" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18287608" "web" => "Medline" ] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0245" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biosimilars: a regulatory perspective from America" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J. Kay" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/ar3310" "Revista" => array:5 [ "tituloSerie" => "Arthritis Res Ther" "fecha" => "2011" "volumen" => "13" "paginaInicial" => "112" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21586106" "web" => "Medline" ] ] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0250" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biosimilars of biological drugs therapies, regulatory, clinical and commercial considerations" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Dranitsaris" 1 => "E. Amir" 2 => "K. Dorward" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2165/11593730-000000000-00000" "Revista" => array:6 [ "tituloSerie" => "Drugs" "fecha" => "2011" "volumen" => "71" "paginaInicial" => "1527" "paginaFinal" => "1536" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21861538" "web" => "Medline" ] ] ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0255" "etiqueta" => "51" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mexico recovers leadership on regulation of biosimilar biotech drugs" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "C. López-Silva" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gac Med Mex" "fecha" => "2012" "volumen" => "148" "paginaInicial" => "83" "paginaFinal" => "90" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22367313" "web" => "Medline" ] ] ] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0260" "etiqueta" => "52" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Etanar therapy in real-life patients with rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Rondon" 1 => "A. Bautista" 2 => "J.C. Salazar" 3 => "N. Casas" 4 => "P. Santos" 5 => "F. Vargas" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2010" "volumen" => "62" "numero" => "Suppl. 10" "paginaInicial" => "1811" ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0265" "etiqueta" => "53" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Dr Reddy's brand of rituximab. Dr Reddy's Laboratories Inc. Website: <a class="elsevierStyleInterRef" href="http://www.drreddys.com/products/pdf/bio/Reditux-splash.pdf">http://www.drreddys.com/products/pdf/bio/Reditux-splash.pdf</a> [accessed 04.04.12]." ] ] ] 53 => array:3 [ "identificador" => "bib0270" "etiqueta" => "54" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "TL011 in Severe, Active Rheumatoid Arthritis Patients. Clinical Trials Website: <a class="elsevierStyleInterRef" href="http://www.clinicaltrials.gov/ct2/show/NCT01123070%3Fterm=TEVA%26cond=arthritis%26rank=2">http://www.clinicaltrials.gov/ct2/show/NCT01123070?term=TEVA&cond=arthritis&rank=2</a>. Accessed February 7, 2012." ] ] ] 54 => array:3 [ "identificador" => "bib0275" "etiqueta" => "55" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Yisaipu Website: <a class="elsevierStyleInterRef" href="http://www.yisaipu.com/DiseaseList.aspx%3Fcate_id=20%26topCateID1=20%26topCateID=15">http://www.yisaipu.com/DiseaseList.aspx?cate_id=20⊤CateID1=20⊤CateID=15</a> [accessed 22.08.12]." ] ] ] 55 => array:3 [ "identificador" => "bib0280" "etiqueta" => "56" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "PRX-106. Protalix Biotherapeutics Website: <a class="elsevierStyleInterRef" href="http://www.protalix.com/product-development/prx-106.asp">http://www.protalix.com/product-development/prx-106.asp</a> [accessed 04.04.12]." ] ] ] 56 => array:3 [ "identificador" => "bib0285" "etiqueta" => "57" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Pipelines. LG Life Sciences Website: <a class="elsevierStyleInterRef" href="http://www.lgls.com/rd/pipeline.jsp">http://www.lgls.com/rd/pipeline.jsp</a> [accessed 04.04.12]." ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:3 [ "identificador" => "xack34611" "titulo" => "Acknowledgments" "texto" => "Editorial/medical writing support was provided by WC Hatch at ACUMED and was funded by Pfizer Inc. No financial support was provided to the authors for this work." ] ] ] "idiomaDefecto" => "en" "url" => "/21735743/0000000900000002/v1_201304200246/S2173574313000130/v1_201304200246/en/main.assets" "Apartado" => array:4 [ "identificador" => "8383" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Review Article" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735743/0000000900000002/v1_201304200246/S2173574313000130/v1_201304200246/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574313000130?idApp=UINPBA00004M"]

Statistics

Review article

Current therapies in rheumatoid arthritis: A Latin American perspective

Las terapias actuales en la artritis reumatoide: una perspectiva latinoamericana

Rubén Burgos-Vargasa,

Corresponding author

r.burgos.vargas@gmail.com

Corresponding author.

, Luis Jose Catoggiob, Claudio Galarza-Maldonadoc, Kasmir Ostojichd, Mario H. Cardiele

a Department of Rheumatology, Hospital General de Mexico, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico

b Rheumatology Section, Medical Services, Hospital Italiano de Buenos Aires, Instituto Universitario Escuela de Medicina Hospital Italiano de Buenos Aires and Fundacion Dr. Pedro M. Catoggio para el Progreso de la Reumatologia, Buenos Aires, Argentina

c Unit of Rheumatic and Autoimmune Diseases UNERA, Lupus Center, Mont Sinai Hospital, Cuenca, Ecuador

d Senior Regional Medical Director, Pfizer Inc., Latin America, Mexico City, Mexico

e Research Unit, Hospital General Dr. Miguel Silva, Morelia, Michoacan, Mexico

Read

9730

Times
was read the article

3113

Total PDF

6617

Total HTML

Share statistics

 array:24 [
  "pii" => "S2173574313000130"
  "issn" => "21735743"
  "doi" => "10.1016/j.reumae.2013.01.007"
  "estado" => "S300"
  "fechaPublicacion" => "2013-03-01"
  "aid" => "507"
  "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;. All rights reserved"
  "copyrightAnyo" => "2012"
  "documento" => "article"
  "crossmark" => 0
  "subdocumento" => "ssu"
  "cita" => "Reumatol Clin. 2013;9:106-12"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:2 [
    "total" => 4287
    "formatos" => array:3 [
      "EPUB" => 48
      "HTML" => 3212
      "PDF" => 1027
    ]
  ]
  "Traduccion" => array:1 [
    "en" => array:19 [
      "pii" => "S1699258X12002525"
      "issn" => "1699258X"
      "doi" => "10.1016/j.reuma.2012.09.001"
      "estado" => "S300"
      "fechaPublicacion" => "2013-03-01"
      "aid" => "507"
      "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;"
      "documento" => "article"
      "crossmark" => 0
      "subdocumento" => "ssu"
      "cita" => "Reumatol Clin. 2013;9:106-12"
      "abierto" => array:3 [
        "ES" => true
        "ES2" => true
        "LATM" => true
      ]
      "gratuito" => true
      "lecturas" => array:2 [
        "total" => 13860
        "formatos" => array:3 [
          "EPUB" => 141
          "HTML" => 11236
          "PDF" => 2483
        ]
      ]
      "en" => array:13 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>"
        "titulo" => "Current therapies in rheumatoid arthritis&#58; A Latin American perspective"
        "tienePdf" => "en"
        "tieneTextoCompleto" => "en"
        "tieneResumen" => array:2 [
          0 => "en"
          1 => "es"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "106"
            "paginaFinal" => "112"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "es" => array:1 [
            "titulo" => "Las terapias actuales en la artritis reumatoide&#58; una perspectiva latinoamericana"
          ]
        ]
        "contieneResumen" => array:2 [
          "en" => true
          "es" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "en" => true
        ]
        "contienePdf" => array:1 [
          "en" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0005"
            "etiqueta" => "Fig&#46; 1"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr1.jpeg"
                "Alto" => 3514
                "Ancho" => 3045
                "Tamanyo" => 722591
              ]
            ]
            "descripcion" => array:1 [
              "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">RA treatment&#46; TF &#40;maximum doses after 8&#8211;12 weeks&#59; DAS28<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>3&#46;2&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Rub&#233;n Burgos-Vargas, Luis Jose Catoggio, Claudio Galarza-Maldonado, Kasmir Ostojich, Mario H&#46; Cardiel"
            "autores" => array:5 [
              0 => array:2 [
                "nombre" => "Rub&#233;n"
                "apellidos" => "Burgos-Vargas"
              ]
              1 => array:2 [
                "nombre" => "Luis Jose"
                "apellidos" => "Catoggio"
              ]
              2 => array:2 [
                "nombre" => "Claudio"
                "apellidos" => "Galarza-Maldonado"
              ]
              3 => array:2 [
                "nombre" => "Kasmir"
                "apellidos" => "Ostojich"
              ]
              4 => array:2 [
                "nombre" => "Mario H&#46;"
                "apellidos" => "Cardiel"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "en"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S2173574313000130"
          "doi" => "10.1016/j.reumae.2013.01.007"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => false
            "ES2" => false
            "LATM" => false
          ]
          "gratuito" => false
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574313000130?idApp=UINPBA00004M"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X12002525?idApp=UINPBA00004M"
      "url" => "/1699258X/0000000900000002/v1_201305061535/S1699258X12002525/v1_201305061535/en/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2173574313000269"
    "issn" => "21735743"
    "doi" => "10.1016/j.reumae.2012.11.003"
    "estado" => "S300"
    "fechaPublicacion" => "2013-03-01"
    "aid" => "514"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;"
    "documento" => "article"
    "crossmark" => 0
    "subdocumento" => "fla"
    "cita" => "Reumatol Clin. 2013;9:113-6"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 5117
      "formatos" => array:3 [
        "EPUB" => 56
        "HTML" => 4115
        "PDF" => 946
      ]
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Special Article</span>"
      "titulo" => "Biosimilar Drugs in Mexico&#58; Position of the Mexican College of Rheumatology&#44; 2012"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "113"
          "paginaFinal" => "116"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Medicamentos biocomparables en M&#233;xico&#58; la postura del Colegio Mexicano de Reumatolog&#237;a&#44; 2012"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Rolando Espinosa Morales, Alejandro D&#237;az Borj&#243;n, Leonor Adriana Barile Fabris, Jorge Antonio Esquivel Valerio, Gabriel Medrano Ram&#237;rez, C&#233;sar Alejandro Arce Salinas, Eduardo Rub&#233;n Barreira Mercado, Mario Humberto Cardiel R&#237;os, Efra&#237;n D&#237;az Jouanen, Francisco Javier Flores Murrieta, Antonio Fraga Mouret, Mario Alberto Garza Elizondo, Miguel Luj&#225;n Estrada, Francisco Jos&#233; Mu&#241;oz Barradas, Juan Osvaldo Talavera Pi&#241;a, Olga Lidia Vera Lastra"
          "autores" => array:16 [
            0 => array:2 [
              "nombre" => "Rolando"
              "apellidos" => "Espinosa Morales"
            ]
            1 => array:2 [
              "nombre" => "Alejandro"
              "apellidos" => "D&#237;az Borj&#243;n"
            ]
            2 => array:2 [
              "nombre" => "Leonor Adriana"
              "apellidos" => "Barile Fabris"
            ]
            3 => array:2 [
              "nombre" => "Jorge Antonio"
              "apellidos" => "Esquivel Valerio"
            ]
            4 => array:2 [
              "nombre" => "Gabriel"
              "apellidos" => "Medrano Ram&#237;rez"
            ]
            5 => array:2 [
              "nombre" => "C&#233;sar Alejandro"
              "apellidos" => "Arce Salinas"
            ]
            6 => array:2 [
              "nombre" => "Eduardo Rub&#233;n"
              "apellidos" => "Barreira Mercado"
            ]
            7 => array:2 [
              "nombre" => "Mario Humberto"
              "apellidos" => "Cardiel R&#237;os"
            ]
            8 => array:2 [
              "nombre" => "Efra&#237;n"
              "apellidos" => "D&#237;az Jouanen"
            ]
            9 => array:2 [
              "nombre" => "Francisco Javier"
              "apellidos" => "Flores Murrieta"
            ]
            10 => array:2 [
              "nombre" => "Antonio"
              "apellidos" => "Fraga Mouret"
            ]
            11 => array:2 [
              "nombre" => "Mario Alberto"
              "apellidos" => "Garza Elizondo"
            ]
            12 => array:2 [
              "nombre" => "Miguel"
              "apellidos" => "Luj&#225;n Estrada"
            ]
            13 => array:2 [
              "nombre" => "Francisco Jos&#233;"
              "apellidos" => "Mu&#241;oz Barradas"
            ]
            14 => array:2 [
              "nombre" => "Juan Osvaldo"
              "apellidos" => "Talavera Pi&#241;a"
            ]
            15 => array:2 [
              "nombre" => "Olga Lidia"
              "apellidos" => "Vera Lastra"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S1699258X12002689"
        "doi" => "10.1016/j.reuma.2012.11.001"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X12002689?idApp=UINPBA00004M"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574313000269?idApp=UINPBA00004M"
    "url" => "/21735743/0000000900000002/v1_201304200246/S2173574313000269/v1_201304200246/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S2173574312001475"
    "issn" => "21735743"
    "doi" => "10.1016/j.reumae.2012.04.012"
    "estado" => "S300"
    "fechaPublicacion" => "2013-03-01"
    "aid" => "457"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;"
    "documento" => "article"
    "crossmark" => 0
    "subdocumento" => "ssu"
    "cita" => "Reumatol Clin. 2013;9:101-5"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 4093
      "formatos" => array:3 [
        "EPUB" => 61
        "HTML" => 3320
        "PDF" => 712
      ]
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Review Article</span>"
      "titulo" => "Treat to Target Strategy in Rheumatoid Arthritis&#58; Real Benefits"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "101"
          "paginaFinal" => "105"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Estrategia &#171;<span class="elsevierStyleItalic">treat to target</span>&#187; en la artritis reumatoide&#58; beneficios reales"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Mario H&#46; Cardiel"
          "autores" => array:1 [
            0 => array:2 [
              "nombre" => "Mario H&#46;"
              "apellidos" => "Cardiel"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S1699258X12001301"
        "doi" => "10.1016/j.reuma.2012.04.004"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X12001301?idApp=UINPBA00004M"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574312001475?idApp=UINPBA00004M"
    "url" => "/21735743/0000000900000002/v1_201304200246/S2173574312001475/v1_201304200246/en/main.assets"
  ]
  "en" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>"
    "titulo" => "Current therapies in rheumatoid arthritis&#58; A Latin American perspective"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "106"
        "paginaFinal" => "112"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Rub&#233;n Burgos-Vargas, Luis Jose Catoggio, Claudio Galarza-Maldonado, Kasmir Ostojich, Mario H&#46; Cardiel"
        "autores" => array:5 [
          0 => array:4 [
            "nombre" => "Rub&#233;n"
            "apellidos" => "Burgos-Vargas"
            "email" => array:1 [
              0 => "r&#46;burgos&#46;vargas&#64;gmail&#46;com"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">¿</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Luis Jose"
            "apellidos" => "Catoggio"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Claudio"
            "apellidos" => "Galarza-Maldonado"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Kasmir"
            "apellidos" => "Ostojich"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Mario H&#46;"
            "apellidos" => "Cardiel"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">e</span>"
                "identificador" => "aff0025"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:5 [
          0 => array:3 [
            "entidad" => "Department of Rheumatology&#44; Hospital General de Mexico&#44; Universidad Nacional Autonoma de Mexico&#44; Mexico City&#44; Mexico"
            "etiqueta" => "<span class="elsevierStyleSup">a</span>"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Rheumatology Section&#44; Medical Services&#44; Hospital Italiano de Buenos Aires&#44; Instituto Universitario Escuela de Medicina Hospital Italiano de Buenos Aires and Fundacion Dr&#46; Pedro M&#46; Catoggio para el Progreso de la Reumatologia&#44; Buenos Aires&#44; Argentina"
            "etiqueta" => "<span class="elsevierStyleSup">b</span>"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Unit of Rheumatic and Autoimmune Diseases UNERA&#44; Lupus Center&#44; Mont Sinai Hospital&#44; Cuenca&#44; Ecuador"
            "etiqueta" => "<span class="elsevierStyleSup">c</span>"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Senior Regional Medical Director&#44; Pfizer Inc&#46;&#44; Latin America&#44; Mexico City&#44; Mexico"
            "etiqueta" => "<span class="elsevierStyleSup">d</span>"
            "identificador" => "aff0020"
          ]
          4 => array:3 [
            "entidad" => "Research Unit&#44; Hospital General Dr&#46; Miguel Silva&#44; Morelia&#44; Michoacan&#44; Mexico"
            "etiqueta" => "<span class="elsevierStyleSup">e</span>"
            "identificador" => "aff0025"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Las terapias actuales en la artritis reumatoide&#58; una perspectiva latinoamericana"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 3411
            "Ancho" => 3045
            "Tamanyo" => 692829
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">RA treatment&#46; TF &#40;maximum doses after 8&#8211;12 weeks&#59; DAS28<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>3&#46;2&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Rheumatoid arthritis &#40;RA&#41; is clinically recognized as an inflammatory process that mainly affects the synovium of joints and tendons and often some extra-articular sites&#46; Classically&#44; the criteria for RA classification relied on the presence of signs and symptoms indicative of inflammatory activity which typically implied irreversible structural damage when present&#46; This situation led to the addition of a new set of classification criteria endorsed by the European League Against Rheumatism &#40;EULAR&#41; and the American College of Rheumatology &#40;ACR&#41; for the diagnosis of RA&#46; The aims of such an initiative were to establish a set of rules to be applied to newly presenting patients with undifferentiated synovitis that would&#58; &#40;1&#41; identify the subset at high risk of chronicity and erosive damage&#59; &#40;2&#41; be used as a basis for initiating disease-modifying therapy&#59; and &#40;3&#41; not exclude the capture of patients later in the disease course&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In this way&#44; early and appropriate disease-modifying treatment&#44; aimed to reduce the risk of joint destruction&#44; could be initiated&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">At first glance&#44; early recognition of patients at risk of erosive RA and swift initiation of treatment should be achievable worldwide&#46; Programs for early diagnosis of patients with undifferentiated arthritis at risk of RA can be instituted at the level of primary health clinics&#46; Once diagnosed&#44; at-risk patients can be treated with disease-modifying antirheumatic drugs &#40;DMARDs&#41; with or without biologic agents with the goal of achieving disease remission and avoiding structural damage&#46; While these goals and strategies have already been launched in the European Union&#44; Canada&#44; and the United States&#44; less progress has been achieved in Latin America&#46; The success of these programs across the world depends on who covers the cost of health care&#46; In Europe and Canada&#44; where health care costs are covered by the state&#44; coverage for RA&#44; for example&#44; depends on the percentage of the health-care budget allocated to rheumatic diseases&#46; In Latin America&#44; the funding situation differs among countries where many state health budgets are limited&#46; Consequently only a fraction of the population has full health coverage&#44; and many patients pay for expenses out of pocket to cover the cost of medical care and insurance&#46; In this sense&#44; the implementation of programs for early detection and treatment of RA might be less successful than in developed countries&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The objectives of this paper are to examine existing treatment practices for RA and discuss the socioeconomic impact of RA from a Latin American perspective&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Epidemiology</span><p id="par0020" class="elsevierStylePara elsevierViewall">There are few reports on the prevalence of RA in Latin America&#46; Recent reports from Argentina show prevalence rates ranging between 0&#46;2&#37; in Tucuman province and the city of Buenos Aires and 0&#46;94&#37; in Lujan province in the province of Buenos Aires&#44; Argentina&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a> The recent epidemiological study on musculoskeletal pain involving 25&#44;587 subjects conducted in five regions in Mexico &#40;Chihuahua&#44; Nuevo Leon&#44; Sinaloa&#44; Yucatan&#44; and Mexico City&#41; showed an overall RA prevalence of 1&#46;6&#37; &#40;95&#37; CI&#58; 1&#46;4&#8211;1&#46;8&#41;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#59; the prevalence in females was 2&#46;0&#37;&#44; while that of males reached 0&#46;8&#37;&#46; The prevalence of RA varied across country regions&#44; specifically&#44; from 0&#46;7 in the Nuevo Le&#243;n state to 2&#46;8&#37; in Yucat&#225;n state&#46; One previous study in M&#233;xico City showed a prevalence of 0&#46;4&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Latin America&#44; with a heterogeneous population estimated at 577 million people&#44; has young adults as the dominant demographic group&#46; RA can start at an early age&#44; as shown by a study comparing patients from Mexico with those from Canada&#46; Mexican patients developed RA almost 12 years earlier than Canadians &#40;95&#37; CI&#58; 9&#8211;15 years&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Almost half of Mexicans&#44; compared with a quarter of Canadians&#44; had their first swollen joint before the age of 36 years&#46; About 4&#37; of Mexicans and 35&#46;5&#37; of Canadians had onset of RA after the age of 55 years &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; RA mainly affects women in their productive years of life&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Socioeconomic impact of rheumatoid arthritis</span><p id="par0030" class="elsevierStylePara elsevierViewall">Latin America&#44; like many other developing regions of the world&#44; has undergone an epidemiological shift from acute to chronic disease as the major contributor to morbidity and mortality&#44; while still confronting problems such as poverty and malnutrition&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Consequently&#44; these changes impact the allocation of health-care resources from acute diseases&#44; such as infections&#44; to chronic diseases such as RA&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> RA is a chronic disease with substantial burden to the patient &#40;reduced function and lower quality of life&#41;&#44; society &#40;loss of productivity through sick leave or permanent work disability &#91;PWD&#93;&#41;&#44; and on health-care resources&#46; <a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> In Mexico&#44; for example&#44; the annual cost of RA and ankylosing spondylitis corresponded to &#36;2900 and &#36;2800 USD&#44; respectively&#44; when direct costs and out-of-the-pocket expenses are considered&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> More recently&#44; we estimated the annual cost of RA per patient in &#36;5534 USD dollars including indirect costs&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The reported prevalence of PWD in the country due to RA is 11&#46;7&#37; and this represents a significant cost to Mexican society and to the Instituto Mexicano del Seguro Social &#40;IMSS&#41;&#44; which is the main health-care provider for salaried workers in the country&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> A lower education level&#44; treatment delay&#44; and positive rheumatoid factor &#40;RF&#41; were shown to increase the risk for PWD in Mexicans with RA&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Health care is typically fragmentary in Latin America&#46; In some countries&#44; the state provides for the majority of health care while in others&#44; individuals pay all or some of the medical expenses&#46; Reimbursement is very limited and is only available in some countries&#46; Access programs are available in some countries where the government usually provides the drug&#46; The coverage varies from 60 to 100&#37; of the population and not all biologics are available&#46; Mexico has the social security or institutional programs of Petr&#243;leos Mexicanos &#40;PEMEX&#41; and Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado&#44; Brazil has Sistema Unico de Saude&#44; Venezuela has the Instituto Venezolano de los Seguros Sociales which offers almost 100&#37; coverage&#44; Colombia has the Entidades Promotoras de Salud&#44; Ecuador has partial and very limited coverage through social security&#44; and Peru has very limited coverage by social security or by other government institutions&#46; Argentina has different governmental and private programs offering different degrees of coverage&#46; In Chile&#44; the public health-care system accounts for 80&#37; of the population while the remaining 20&#37; is covered by private health care&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Early treatment of RA translates into substantial reduction in the cost to society&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> In light of this&#44; early disease clinics are being established in some countries&#44; including Argentina&#44; Colombia&#44; Brazil&#44; Mexico&#44; and Peru&#46; A Colombian study showed that the time to referral from primary to tertiary care for RA patients improved from 1998 to 2002 with the introduction of early disease clinics&#59; 54&#37; of patients were referred within 3&#8211;6 months of diagnosis by 2002 and DMARDs were shown to be the leading first-line and second-line treatment options&#44; with biologics accounting for 16&#37; of second-line prescriptions in 2002&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In Argentina&#44; the Consorcio Argentino de Artritis Temprana database was established that specifically focuses on patients with early RA &#40;ERA&#41; to provide further data on detection and appropriate follow-up&#46; Preliminary results showed a frank reduction in disease duration at referral in less than two years&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Barriers identified in the management of RA include inadequate health-care access and referral delays due to the lack of training of general practitioners in musculoskeletal problems&#44; a shortage and inadequate distribution of rheumatologists in some countries&#44; and limited access to appropriate therapy&#46; There is also a lack of patient databases or registries for rheumatic patients in most of the Latin American countries&#46; Additional factors contributing to poor patient prognosis include low socioeconomic status&#44; disease related factors &#40;e&#46;g&#46;&#44; severity&#44; joint damage&#44; comorbidities&#41;&#44; and cost of treatment&#46; In one study&#44; it was reported that 15&#37; of the family income goes to RA-related expenses and this represents 26&#46;1&#37; of the total annual cost per RA patient&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In a study of 262 patients with RA in Mexico&#44; the RA annual cost reported was USD 5534&#46;80 per patient&#59; 65&#37; were direct costs &#40;physician consultations&#44; hospitalization&#44; medication&#44; and alternative therapies as well as laboratory and auxiliary tests&#44; transportation and meals related to medical care&#41; and 35&#37; were indirect costs &#40;work disability&#44; home care&#44; and loss of income at home&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> which are similar in distribution to what has been reported in Europe&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> RA out of pocket costs caused catastrophic expenses in 46&#46;9&#37; of households which were associated with the type of health-care coverage &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;7&#44; 95&#37; CI&#58; 1&#46;6&#8211;4&#46;7&#41; and disease duration &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;024&#44; 95&#37; CI&#58; 1&#46;002&#8211;1&#46;046&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Impoverishment&#44; measured by the household inability to cover the basic food basket threshold in Mexico&#44; occurred in 66&#46;8&#37; of households and was associated with catastrophic expenses &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#46;6&#44; 95&#37; CI&#58; 1&#46;04&#8211;14&#46;1&#41;&#44; high health assessment questionnaire &#40;HAQ&#41; scores and low socioeconomic levels&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> An analysis utilizing the Quantitative Standard Monitoring of Patients with RA database cohort of 6004 patients from 25 countries evaluated the disparities of RA disease activity with gross domestic product &#40;GDP&#41; of a country&#46; It found the burden of RA was substantially greater in low GDP than in high GDP countries&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> In Latin America &#40;which has a significantly lower GDP than Europe&#44; the United States&#44; or Canada&#41;&#44; the cost of biologics in general is very similar to countries with higher GDP&#44; further impairing access to these medications&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Latin American clinical criteria for the use and selection of biologics and treatment strategies</span><p id="par0050" class="elsevierStylePara elsevierViewall">In 2006&#44; the Latin American Rheumatology Associations of the Pan-American League of Associations for Rheumatology &#40;PANLAR&#41; and the Grupo Latino Americano de Estudio de Artritis Reumatoide &#40;GLADAR&#41; issued the first Latin American position paper on the pharmacological treatment of RA that advocated for early aggressive therapy for RA patients&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Efforts were focused on the issues facing the region with regards to the availability of appropriate treatment for RA and the development of treatment guidelines &#40;shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; that can be used for clinical practice&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Subsequently&#44; PANLAR and GLADAR issued a consensus position paper on the management of patients with RA in Latin America in 2009&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> establishing the following criteria for using biologic agents in RA patients who were unresponsive to DMARDs&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Patients having the diagnosis of RA according to ACR criteria&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Active disease measured by a disease activity scale such as disease activity score in 28 joints &#40;DAS28&#41; &#8805;3&#46;2 and after at least 3 months on conventional treatment with DMARDS&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0070" class="elsevierStylePara elsevierViewall">Patients should have used two DMARDs&#44; one being methotrexate &#40;MTX&#41; in adequate doses&#44; unless there were significant adverse effects&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Adequate doses of MTX should have been up to 25<span class="elsevierStyleHsp" style=""></span>mg weekly via oral&#44; intramuscular&#44; or subcutaneous &#40;SC&#41;&#44; and leflunomide 20<span class="elsevierStyleHsp" style=""></span>mg per day&#59; with the exception of patients presenting adverse events &#40;AEs&#41; limiting the use of these therapies&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Patients should be in functional ACR status I&#44; II&#44; or III&#46;</p></li></ul></p><p id="par0085" class="elsevierStylePara elsevierViewall">GLADAR also developed evidence-based guidelines specific for the use of rituximab in the treatment of RA in Latin America&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> GLADAR recommends rituximab in patients with active &#40;DAS28<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>3&#46;2&#41; RF-positive RA who had inadequate response or intolerance to an adequate course as previously defined with tumor necrosis factor &#40;TNF&#41; inhibitors&#46; Rituximab can also be used in patients who have inadequate response or intolerance to more than one conventional DMARD and cannot receive TNF inhibitors &#40;due to contraindications or unavailability&#41;&#46; Based on lack of strong evidence&#44; rituximab cannot be recommended to RF-negative RA patients&#59; GLADAR&#44; however&#44; recommends that RF-negative patients be considered for treatment if they meet the conventional treatment failure criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Some countries have developed their own treatment guidelines for RA based on the PANLAR&#47;GLADAR guidelines but adapted to their own situations&#46; In Argentina&#44; clinical practice guidelines for RA were developed by the Argentine Society of Rheumatology in 2003 and were updated in 2008&#46; It has since undergone annual updates to keep up with the continuing advances in the understanding of the pathogenesis&#44; evolution&#44; and treatment of RA to include new diagnostic technologies and new drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> In Brazil&#44; the Brazilian Society of Rheumatology &#40;SBR&#41; published the &#8220;Brazilian Consensus for the Diagnosis and Treatment of RA&#8221; in the 2004 Brazilian Journal of Rheumatology&#46; The consensus was updated in 2007 to include grades of recommendations and strength of evidence based on the previous work of SBR&#44; the experiences of rheumatologists&#44; and literature review&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> In Chile&#44; the Ministry of Health issued the RA Clinical Guide Series in 2007 which included flow diagrams in the management of patients with RA and early diagnosis&#44; referral&#44; and treatment among its key recommendations&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> In Colombia&#44; the Colombian Association of Rheumatology published the first edition of the &#8220;Guidelines for the Treatment of RA&#8221; in 2002&#46; The guidelines were intended to minimize clinical variability of managing RA and to facilitate the clinical evaluation&#44; financial&#44; and legal processes&#44; as well as streamlining cost associated with RA treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> In Costa Rica&#44; the Costa Rican Association of Rheumatology and the College of Physicians and Surgeons developed the &#8220;Guidelines for the Management of RA&#8221; 2010 Consensus&#44; which considered the severity of RA as a disease that can eventually be modified and the need for close monitoring of the patient preferably by a rheumatologist&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> In Mexico&#44; the Mexican College of Rheumatology issued guidelines and recommendations in 2006<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> and the IMSS published guidelines in 2010 for the treatment of RA recommending biologics&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Current clinical practice</span><p id="par0095" class="elsevierStylePara elsevierViewall">Latin American rheumatologists are aware of the importance of early detection and diagnosis of RA and the short- and long-term efficacy of DMARD or DMARD plus biologic agents&#46; However&#44; the implementation of early detection clinics and early treatment can be difficult because of inadequate financial resources needed to fund such programs&#46; One of several strategies to minimize cost of early detection and treatment would be combining the presumptive diagnosis of RA by a rheumatologist with the presence of anti-cyclic citrullinated peptides &#40;CCP&#41; antibodies&#46; Such combination was shown to be highly specific for diagnosing RA in patients with very early arthritis&#46; The sensitivity and specificity of prediction by a rheumatologist were 94&#37; and 74&#37;&#44; respectively&#59; for anti-CCP antibodies&#44; they were 56&#37; and 96&#37;&#44; respectively&#46; Combining the two variables resulted in a specificity of 100&#37; and a sensitivity of 53&#37;&#44; and a positive predictive value of 98&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">While debate exists about when is the best time to start treatment &#40;within 3&#44; 6&#44; or 12 months&#41;&#44; the aim is to treat as early as possible&#44; according to patient needs&#46; Treat-to-target with the objective of disease remission and&#47;or low disease activity &#40;LDA&#41; score is practiced in some clinics in the region&#59; close monitoring of AEs and consideration of patient comorbidities are necessary&#46; It is important to consider each patient individually and to adopt practical strategies to meet their needs&#46; Tight control strategies versus &#8220;routine&#8221; practice has been assessed in studies&#44; suggesting that intensive patient management and treating to target reduce disease activity and radiographic progression compared with routine or symptomatic outpatient care&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;31</span></a></p><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Very early rheumatoid arthritis&#47;early rheumatoid arthritis</span><p id="par0105" class="elsevierStylePara elsevierViewall">Expert consensus defined very early RA as the RA occurring between 3 and 4&#8211;6 months and early RA &#40;ERA at one year&#41;&#46; Early diagnosis of RA can be difficult because patients who have very recent onset arthritis &#40;&#8804;12 weeks of evolution&#41; may have been diagnosed with other diseases&#44; including self-limited arthritis&#46; Hence&#44; the sensitivity and specificity of classification criteria for RA established by the ACR are not effective for this particular group of RA patients&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> Further&#44; 80&#46;4&#37; of early inflammatory arthritis was shown to progress to persistent arthritis&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">For the management of early arthritis or ERA&#44; the EULAR task force of the European Standing Committee for International Clinical Studies Including Therapeutics &#40;ESCISIT&#41; developed a set of 12 recommendations based on evidence in the literature and expert consensus&#59; detailed descriptions are published elsewhere&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Biologic registries</span><p id="par0115" class="elsevierStylePara elsevierViewall">Educating the physicians&#44; patients&#44; community&#44; and policy makers is important in RA treatment&#46; Equally important is maintaining accurate records on all aspects of prescribed biologics&#44; particularly on AEs and treatment duration&#46; The establishment of local disease registries addresses this need and provides a better understanding of rheumatic disease and its treatment in the region&#46; To address safety concerns&#44; the Pan-American Registry of AEs of Biological Therapies in Rheumatic Diseases was established in 2007 as a collaboration between PANLAR and the Sociedad Espa&#241;ola de Reumatolog&#237;a &#40;SER&#41;&#46; It is considered an important resource to monitor biologic-related AEs in the Latin American region&#46; This registry includes data on 1481 rheumatic-disease patients available from 1998 to 2009&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> Some country-specific biologics registries include BIOBADASAR &#40;Argentina&#41;&#44; established in 2010&#44; BIOBADABRASIL &#40;Brazil&#41; and BIOBADAMEX &#40;Mexico&#41;&#44; both established in 2008&#46; The implementation and maintenance of these registries require substantial funding and monitoring&#46; Although initially established by national societies of rheumatology&#44; registries also receive financial support from pharmaceutical manufacturers &#40;e&#46;g&#46;&#44; BIOBADABRASIL&#41; and essential academic support from SER&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Prescribing biologics in Latin America</span><p id="par0120" class="elsevierStylePara elsevierViewall">Rheumatologists in Latin America have clinical experience in treating RA patients who have access with TNF inhibitors and other biologics&#46; Patients were treated with biologics after experiencing MTX failure&#44; multiple DMARD failures and experiencing early&#44; aggressive RA who are both MTX and biologic na&#239;ve following regional guidelines&#46; A list of the biologic agents for the treatment of RA in Latin America is presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Future therapies</span><p id="par0125" class="elsevierStylePara elsevierViewall">Kinase inhibitors currently under investigation for RA include tofacitinib &#40;CP-690&#44;550&#41; and fostamatinib &#40;R788&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">41&#44;42</span></a> Tofacitinib is a janus kinase inhibitor shown in phase 3 trials to be effective in patients with moderate to severe active RA&#59; ACR50 response rates at month 6 of up to 37&#37; in tofacitinib versus 12&#37; in placebo patients who had inadequate response to MTX were achieved with improvement in pain and physical function compared with placebo&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> Fostamatinib &#40;R788&#41; is a spleen tyrosine kinase inhibitor that was evaluated in a 6-month&#44; double-blind&#44; placebo controlled trial in patients with active RA and on long-term MTX therapy&#46; Results showed ACR50 response rates of up to 43&#37; in fostamatinib patients versus 19&#37; in placebo patients&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> Other biologic agents for future consideration in Latin America include the monoclonal antibodies golimumab and certolizumab pegol&#46; Golimumab was shown in a randomized&#44; double-blind&#44; placebo-controlled phase 3 trial to reduce the signs and symptoms of RA in patients who received prior TNF-inhibitor therapy&#59; ACR20 was achieved at week 14 by 35&#37; and 38&#37; of patients on 50<span class="elsevierStyleHsp" style=""></span>mg and 100<span class="elsevierStyleHsp" style=""></span>mg&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a> Certolizumab pegol plus MTX was shown in a randomized&#44; double-blind&#44; placebo-controlled phase 3 trial to be more efficacious than placebo in patients with active RA who achieved an ACR20 response&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> Certolizumab pegol is expected to be approved in Chile and Mexico in 2012&#59; its approval is pending in Argentina and Ecuador&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Biosimilars</span><p id="par0130" class="elsevierStylePara elsevierViewall">Biosimilars are biopharmaceuticals that may be similar to the innovator product and enter the market when the patent of the original biologic product expires &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Although the development of biosimilar or &#8220;follow on&#8221; proteins is expensive&#44; an estimated 30&#37; of costs can be saved on current patented biologics&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a> While biosimilars are comparable to their biologic counterparts in safety and efficacy&#44;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a> they are not identical due to the manufacturing process&#44; which is more complex than that of generic small molecule products&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a> Minor changes present in biosimilars could be immunogenic&#44; thus possibly interfering with efficacy and safety&#46; As such&#44; efficacy and safety data of biologics should not be extrapolated to biosimilars&#59; neither should biologics and biosimilars be considered interchangeable unless strict biochemical and clinical studies with long term evaluation are performed&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> Furthermore long term safety of either agent cannot be adequately assessed if patients change a biologic for a biosimilar or vice versa&#46; Pharmacovigilance is particularly important with the use of any biologic&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> Biosimilars should be considered interchangeable with the original product only after sufficient clinical data and marketplace experience have been accrued&#46; Approval of biosimilars should be tightly regulated and require direct head-to-head toxicological&#44; nonclinical&#44; and clinical data in comparison to the reference biologic&#46; Regulatory aspects are particularly important&#44; and clinicians should be included in the review process&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">Colombia in Latin America had approved the etanercept biosimilar&#44; Etanar&#44; for the treatment of inflammatory diseases&#44; although regulations for the approval of biosimilars are still under development&#46; In 2006&#44; Etanar was imported to Colombia from China&#44; approved for the treatment of RA&#44; and was made available through the social security system&#46; In Colombia&#44; the efficacy and safety of Etanar &#40;25<span class="elsevierStyleHsp" style=""></span>mg SC twice weekly&#41; were shown in a multicenter&#44; observational before-after study involving 110 patients with active RA despite treatment with DMARDs who were followed for 20 weeks&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a> DAS28 decreased from 5&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;81 to 3&#46;48<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;12 &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; and HAQ decreased from 2&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;1 to 1&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9 &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; Side effects were reported in 10&#37; of patients&#46; Reasons for discontinuation were lack of efficacy&#44; heart failure&#44; nausea&#44; dizziness&#44; pneumonia&#44; and asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Recently Reditux&#44; a rituximab biosimilar produced by Dr Reddy&#39;s Laboratories &#40;India&#41; has become available in some countries of Latin America including Peru&#44; Ecuador&#44; Chile&#44; Bolivia&#44; and Venezuela&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a></p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusions</span><p id="par0145" class="elsevierStylePara elsevierViewall">In summary&#44; it is clear that the policy of most Latin American academic rheumatologists is to diagnose as early as possible&#44; treat early with conventional DMARDs alone or in combination&#44; aim at remission or LDA &#40;treat-to-target&#41; and then add biologics if disease control is not adequate&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Management of RA has a defined treatment pattern that is adjusted based on patients&#8217; response to therapy&#46; Typically&#44; MTX is the initial therapy and&#44; in the case of inadequate response or adverse reaction&#44; is followed by adding in combinations of other DMARDs&#46; This is then followed by biologics&#44; which are either cycled&#44; in the case of TNF-&#945; inhibitors&#44; or changed based on their mechanism of action&#46; The concept of early treatment and treat-to-target are well recognized in academic rheumatology but still need to be established in general practitioners&#8217; minds and payers&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Challenges for Latin American countries&#44; as in other parts of the world&#44; in the treatment of RA include making RA a public health priority&#44; knowing its socioeconomic impact in terms of its high cost and burden on the health-care system&#44; and increasing access to prompt diagnosis&#44; treatment by rheumatologists&#44; and availability of effective low cost medications&#46; Other issues of concern include regularly updating guidelines&#44; developing treatment algorithms based on local needs and resources&#44; establishing routine epidemiological surveillance&#44; and educating the people&#44; patients&#44; and health-care providers&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Ethical disclosures</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Protection of human and animal subjects</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this investigation&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Confidentiality of data</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Right to privacy and informed consent</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0175" class="elsevierStylePara elsevierViewall">Rub&#233;n Burgos Vargas has participated on advisory boards for Abbott&#44; BMS&#44; Jannsen&#44; Pfizer&#44; and Roche&#44; and as a speaker for Abbott&#44; BMS&#44; Jannsen&#44; Pfizer&#44; and Roche&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Kasmir Ostojich was a Regional Medical Director of Medical Affairs for Pfizer Inc&#44; Inflammation during the development of this manuscript&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Mario H&#46; Cardiel is a clinical researcher who has conducted clinical trials for Pfizer&#44; Roche&#44; Bristol Myers Squibb&#44; La Jolla Pharmaceutical&#44; Anthera&#44; Astra Zeneca&#44; Chelsea&#46; He has been a speaker and consultant for Pfizer&#44; Bristol Myers Squibb&#44; Abbott and Merck&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:14 [
        0 => array:2 [
          "identificador" => "xres90923"
          "titulo" => "Abstract"
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec78147"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "xres90922"
          "titulo" => "Resumen"
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec78146"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Epidemiology"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Socioeconomic impact of rheumatoid arthritis"
        ]
        7 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Latin American clinical criteria for the use and selection of biologics and treatment strategies"
        ]
        8 => array:3 [
          "identificador" => "sec0025"
          "titulo" => "Current clinical practice"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Very early rheumatoid arthritis&#47;early rheumatoid arthritis"
            ]
            1 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Biologic registries"
            ]
            2 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Prescribing biologics in Latin America"
            ]
            3 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Future therapies"
            ]
            4 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Biosimilars"
            ]
          ]
        ]
        9 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Conclusions"
        ]
        10 => array:3 [
          "identificador" => "sec0060"
          "titulo" => "Ethical disclosures"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Protection of human and animal subjects"
            ]
            1 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Confidentiality of data"
            ]
            2 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Right to privacy and informed consent"
            ]
          ]
        ]
        11 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Conflict of interest"
        ]
        12 => array:2 [
          "identificador" => "xack34611"
          "titulo" => "Acknowledgments"
        ]
        13 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2012-04-23"
    "fechaAceptado" => "2012-09-08"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec78147"
          "palabras" => array:5 [
            0 => "Rheumatoid arthritis"
            1 => "Latin America"
            2 => "Socioeconomic factors"
            3 => "Practice guidelines"
            4 => "Biologic therapy"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec78146"
          "palabras" => array:5 [
            0 => "Artritis reumatoide"
            1 => "Am&#233;rica Latina"
            2 => "Factores socioecon&#243;micos"
            3 => "Gu&#237;as de pr&#225;ctica cl&#237;nica"
            4 => "Terapia biol&#243;gica"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Rheumatoid arthritis &#40;RA&#41; is a systemic inflammatory disease affecting the synovium of joints&#44; tendons&#44; and some extra-articular sites&#46; RA prevalence in Latin America ranges from 0&#46;4 to 1&#46;6&#37;&#46; Early treatment of RA translates into a substantial reduction in the cost to society&#46; In light of this&#44; early disease clinics are being established in some countries&#46; Barriers to RA management&#44; such as delay in referral to rheumatologists and limited access to therapy&#44; have been identified&#46; Evidence-based treatment guidelines have been adapted by countries according to their own situations&#46; The need for keeping accurate records of biologics prescribed has been addressed by biologic registries&#44; thereby contributing toward a better understanding of rheumatic diseases and their treatment&#46; Current biologics include the tumor necrosis factor &#40;TNF&#41;-&#945; inhibitors &#40;etanercept&#44; infliximab&#44; and adalimumab&#41;&#44; B-cell depletion agent &#40;rituximab&#41;&#44; interleukin-6 receptor blocker &#40;tocilizumab&#41;&#44; and T-cell co-stimulatory blocker &#40;abatacept&#41;&#46; Future therapies include kinase inhibitors &#40;tofacitinib and fostamatinib&#41;&#44; alternative TNF-&#945; inhibitors &#40;golimumab and certolizumab&#41;&#44; and biosimilars&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La artritis reumatoide &#40;AR&#41; es una enfermedad sist&#233;mica e inflamatoria que afecta la membrana sinovial de las articulaciones&#44; los tendones y algunos sitios extra-articulares&#46; La prevalencia de la AR en Latinoam&#233;rica se encuentra entre 0&#46;4&#8211;1&#46;6&#37;&#46; El tratamiento precoz de la enfermedad se traduce en una reducci&#243;n del costo para la sociedad&#46; En vista de esto&#44; se han establecido cl&#237;nicas de AR temprana en varios pa&#237;ses de la regi&#243;n&#46; Se han identificado barreras para el tratamiento de la AR como lo son el retraso en la referencia al reumat&#243;logo y limitaciones en el acceso al tratamiento&#46; Varios pa&#237;ses han desarrollado y adaptado gu&#237;as para el tratamiento basadas en la evidencia y en sus propias realidades&#46; La necesidad de tener registros detallados de las prescripciones de biol&#243;gicos ha sido abordada con registros de biol&#243;gicos lo que llevar&#225; a un mejor entendimiento de las enfermedades reum&#225;ticas y su tratamiento&#46; Los biol&#243;gicos disponibles en la actualidad son los inhibidores del factor de necrosis tumoral &#40;TNF&#41;-&#945; &#40;etanercept&#44; infliximab y adalimumab&#41;&#44; un agente depletor de c&#233;lulas B &#40;rituximab&#41;&#44; un bloqueador del receptor de interleucina-6 &#40;tocilizumab&#41; y un bloqueador de la co-estimulaci&#243;n de c&#233;lulas T &#40;abatacept&#41;&#46; En el futuro se incluir&#225;n los inhibidores de cinasas &#40;tofacitinib y fostamatinib&#41; e inhibidores del TNF-&#945; alternativos &#40;golimumab y certolizumab&#41; y biosimilares&#46;</p>"
      ]
    ]
    "multimedia" => array:3 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 3411
            "Ancho" => 3045
            "Tamanyo" => 692829
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">RA treatment&#46; TF &#40;maximum doses after 8&#8211;12 weeks&#59; DAS28<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>3&#46;2&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">RA&#44; rheumatoid arthritis&#59; TNF&#44; tumor necrosis factor&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Mechanism of action&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Biologic agents&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TNF-&#945; inhibitors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etanercept&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> infliximab&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> adalimumab<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B-cell depletion agent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rituximab<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T-cell co-stimulatory blockers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Abatacept<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cytokine inhibitor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tocilizumab<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab176524.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Biologic agents for the treatment of RA in Latin America&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">RA&#44; rheumatoid arthritis&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Biosimilar&#47;company&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Current status&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Original product &#40;biologic&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TL011&#47;Teva Pharmaceutical Industries Ltd&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Phase 1 and 2 clinical trials&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rituxan &#40;rituximab&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reditux&#47;Dr Reddy&#39;s Laboratories<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Launched in 2007 and is marketed in India and several other countries&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rituxan &#40;rituximab&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yisaipu&#47;Shanghai CP Guojian Pharmaceuticals Co&#46;&#44; Ltd&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">In use in China since 2005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Enbrel &#40;etanercept&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etanar&#47;Lafrancol<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">In use in Colombia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Enbrel &#40;etanercept&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PRX-106&#47;Protalix Biotherapeutics<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Preclinical&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Enbrel &#40;etanercept&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TNFcept&#47;LG Life Sciences<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Phase 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Enbrel &#40;etanercept&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TNFmab&#47;LG Life Sciences<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Preclinical&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Remicade &#40;infliximab&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab176525.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Biosimilar agents for the treatment of RA&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:57 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rheumatoid arthritis classification criteria&#58; an American College of Rheumatology&#47;European League Against Rheumatism collaborative initiative"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Aletaha"
                            1 => "T&#46; Neogi"
                            2 => "A&#46;J&#46; Silman"
                            3 => "J&#46; Funovits"
                            4 => "D&#46;T&#46; Felson"
                            5 => "C&#46;O&#46; Bingham IIIrd"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.27584"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2010"
                        "volumen" => "62"
                        "paginaInicial" => "2569"
                        "paginaFinal" => "2581"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20872595"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence of rheumatoid arthritis in Tucum&#225;n&#44; Argentina"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Spindler"
                            1 => "V&#46; Bellomio"
                            2 => "A&#46; Berman"
                            3 => "E&#46; Lucero"
                            4 => "M&#46; Baigorria"
                            5 => "S&#46; Paz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Rheumatol"
                        "fecha" => "2002"
                        "volumen" => "29"
                        "paginaInicial" => "1166"
                        "paginaFinal" => "1170"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12064829"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Health care utilization and direct medical costs in patients with rheumatoid arthritis in a developing country"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46;R&#46; Soriano"
                            1 => "C&#46; Castel del Cid"
                            2 => "F&#46; Devoto"
                            3 => "P&#46; Imamura"
                            4 => "L&#46; Catoggio"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Rheumatology"
                        "fecha" => "2005"
                        "volumen" => "44"
                        "paginaInicial" => "i54"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The prevalence of rheumatoid arthritis in Argentina&#58; a capture-recapture study in a city in Buenos Aires province"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Scublinsky"
                            1 => "H&#46; Venarotti"
                            2 => "G&#46; Citera"
                            3 => "O&#46;D&#46; Messina"
                            4 => "E&#46; Scheines"
                            5 => "O&#46; Rillo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/RHU.0b013e3181f3bfdd"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Rheumatol"
                        "fecha" => "2010"
                        "volumen" => "16"
                        "paginaInicial" => "317"
                        "paginaFinal" => "321"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20859227"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology of the rheumatic diseases in Mexico&#46; A study of 5 regions based on the COPCORD methodology"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "I&#46; Pel&#225;ez-Ballestas"
                            1 => "L&#46;H&#46; Sanin"
                            2 => "J&#46; Moreno-Montoya"
                            3 => "J&#46; Alvarez-Nemegyei"
                            4 => "R&#46; Burgos-Vargas"
                            5 => "M&#46; Garza-Elizondo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3899/jrheum.100951"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Rheumatol Suppl"
                        "fecha" => "2011"
                        "volumen" => "86"
                        "paginaInicial" => "3"
                        "paginaFinal" => "8"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21196592"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Community based study to estimate prevalence&#44; burden of illness and help seeking behavior in rheumatic diseases in Mexico City&#46; A COPCORD study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;H&#46; Cardiel"
                            1 => "J&#46; Rojas-Serrano"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Exp Rheum"
                        "fecha" => "2002"
                        "volumen" => "20"
                        "paginaInicial" => "617"
                        "paginaFinal" => "662"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Latitude gradient influences the age of onset of rheumatoid arthritis patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Ramos-Remus"
                            1 => "G&#46; Sierra-Jimenez"
                            2 => "K&#46; Skeith"
                            3 => "F&#46;J&#46; Aceves-Avila"
                            4 => "A&#46;S&#46; Russell"
                            5 => "R&#46; Offer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10067-007-0666-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Rheumatol"
                        "fecha" => "2007"
                        "volumen" => "26"
                        "paginaInicial" => "1725"
                        "paginaFinal" => "1728"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17646901"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Challenges in the management of rheumatoid arthritis in developing countries"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "G&#46;M&#46; Mody"
                            1 => "M&#46;H&#46; Cardiel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.berh.2008.04.003"
                      "Revista" => array:6 [
                        "tituloSerie" => "Best Pract Res Clin Rheumatol"
                        "fecha" => "2008"
                        "volumen" => "22"
                        "paginaInicial" => "621"
                        "paginaFinal" => "641"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18783741"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Bloomberg School of Public Health&#44; Johns Hopkins University&#46; Non-communicable chronic diseases in Latin America and the Caribbean&#46; The Healthy Caribbean Coalition Website&#58; <a class="elsevierStyleInterRef" href="http://www.healthycaribbean.org/publications/documents/NCD-in-LAC-USAID.pdf">http&#58;&#47;&#47;www&#46;healthycaribbean&#46;org&#47;publications&#47;documents&#47;NCD-in-LAC-USAID&#46;pdf</a> &#91;accessed 13&#46;11&#46;11&#93;&#46;"
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The burden of illness of rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Boonen"
                            1 => "J&#46;L&#46; Severens"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10067-010-1634-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Rheumatol"
                        "fecha" => "2011"
                        "volumen" => "30"
                        "paginaInicial" => "S3"
                        "paginaFinal" => "S8"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21359507"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Social costs of the most common inflammatory rheumatic disease in Mexico from the patient&#39;s perspective"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Mould-Quevedo"
                            1 => "I&#46; Pel&#225;ez-Ballestas"
                            2 => "J&#46; V&#225;squez-Mellado"
                            3 => "L&#46; Ter&#225;n-Estrada"
                            4 => "J&#46; Esquivel-Valerio"
                            5 => "L&#46; Ventura-R&#237;os"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Gac Med Mex"
                        "fecha" => "2008"
                        "volumen" => "144"
                        "paginaInicial" => "225"
                        "paginaFinal" => "231"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18714591"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Catastrophic expenses and rate of impoverishment as consequence of the cost of rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46; &#193;lvarez-Hern&#225;ndez"
                            1 => "I&#46; Pelaez-Ballestas"
                            2 => "A&#46; Boonen"
                            3 => "J&#46; V&#225;zquez-Mellado"
                            4 => "A&#46; Hern&#225;ndez-Gardu&#241;o"
                            5 => "F&#46; Carlos"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.reuma.2012.05.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Reumatol Clin"
                        "fecha" => "2012"
                        "volumen" => "8"
                        "paginaInicial" => "168"
                        "paginaFinal" => "173"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22704914"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Factors associated with permanent work disability in Mexican patients with rheumatoid arthritis&#46; A case control study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46; Morales-Romero"
                            1 => "L&#46; Gonzales-Lopez"
                            2 => "A&#46; Celis"
                            3 => "B&#46;E&#46; Rodriguez-Arreola"
                            4 => "C&#46;E&#46; Cabrera-Pivaral"
                            5 => "J&#46;I&#46; Gamez-Nava"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Rheumatol"
                        "fecha" => "2006"
                        "volumen" => "33"
                        "paginaInicial" => "1247"
                        "paginaFinal" => "1249"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16758509"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The costs of rheumatoid arthritis&#58; an international long-term view"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "K&#46;M&#46; Pugner"
                            1 => "D&#46;I&#46; Scott"
                            2 => "J&#46;W&#46; Holmes"
                            3 => "K&#46; Hieke"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Semin Arthritis Rheum"
                        "fecha" => "2000"
                        "volumen" => "29"
                        "paginaInicial" => "305"
                        "paginaFinal" => "320"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10805355"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Utilizaci&#243;n de medicinas alternativas en la consulta reumatol&#243;gica en la ciudad de Barranquilla"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Caballero-Uribe"
                            1 => "H&#46; Wilches"
                            2 => "K&#46; Wilches"
                            3 => "J&#46; Rojas"
                            4 => "J&#46; Salas Siado"
                            5 => "E&#46; Forero"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Col Rheumatol"
                        "fecha" => "2002"
                        "volumen" => "9"
                        "paginaInicial" => "194"
                        "paginaFinal" => "200"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "General characteristics of an early arthritis cohort in Argentina"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Marcos"
                            1 => "C&#46; Waimann"
                            2 => "F&#46; Dal Pra"
                            3 => "J&#46; Hogrefe"
                            4 => "S&#46; Retamozo"
                            5 => "F&#46; Caeiro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rheumatology &#40;Oxford&#41;"
                        "fecha" => "2011"
                        "volumen" => "50"
                        "paginaInicial" => "110"
                        "paginaFinal" => "116"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The burden of rheumatoid arthritis and access to treatment&#58; health burden and costs"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46; Lundkvist"
                            1 => "F&#46; Kast&#228;ng"
                            2 => "G&#46; Kobelt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10198-007-0088-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Health Econ"
                        "fecha" => "2008"
                        "volumen" => "8"
                        "paginaInicial" => "S49"
                        "paginaFinal" => "S60"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18157732"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; Sokka"
                            1 => "H&#46; Kautiainen"
                            2 => "T&#46; Pincus"
                            3 => "S&#46; Toloza"
                            4 => "G&#46; da Rocha Castelar Pinheiro"
                            5 => "J&#46; Lazovskis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2009.109983"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2009"
                        "volumen" => "68"
                        "paginaInicial" => "1666"
                        "paginaFinal" => "1672"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19643759"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "First Latin American position paper on the pharmacological treatment of rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "M&#46;H&#46; Cardiel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rheumatology &#40;Oxford&#41;"
                        "fecha" => "2006"
                        "volumen" => "45"
                        "paginaInicial" => "ii7"
                        "paginaFinal" => "ii22"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Management of patients with rheumatoid arthritis in Latin America&#46; A Consensus position paper from Pan-American League of Associations of Rheumatology and Grupo Latino Americano de Estudio de Artritis Reumatoide"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Massardo"
                            1 => "M&#46;E&#46; Suarez-Almazor"
                            2 => "M&#46;H&#46; Cardiel"
                            3 => "A&#46; Nava"
                            4 => "R&#46;A&#46; Levy"
                            5 => "I&#46; Laurindo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/RHU.0b013e3181a90cd8"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Rheumatol"
                        "fecha" => "2009"
                        "volumen" => "15"
                        "paginaInicial" => "203"
                        "paginaFinal" => "210"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19502907"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Guidelines&#46; Use of rituximab for the treatment of rheumatoid arthritis&#58; the Latin American context"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;R&#46; Soriano"
                            1 => "C&#46; Galarza-Maldonado"
                            2 => "M&#46;H&#46; Cardiel"
                            3 => "B&#46;A&#46; Pons-Estel"
                            4 => "L&#46; Massardo"
                            5 => "C&#46;V&#46; Caballero-Uribe"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/rheumatology/ken015a"
                      "Revista" => array:6 [
                        "tituloSerie" => "Rheumatology"
                        "fecha" => "2008"
                        "volumen" => "47"
                        "paginaInicial" => "1097"
                        "paginaFinal" => "1099"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18463144"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Sociedad Argentina de Reumatolog&#237;a&#46; Gu&#237;as argentinas de pr&#225;ctica cl&#237;nica en el tratamiento de la artritis reumatoide&#58; Actualizaci&#243;n&#46; Revista Argentina de Reumatolog&#237;a&#46; <a class="elsevierStyleInterRef" href="http://www.reumatologia.org.ar/userfiles/file/publicaciones/revista-reumatologia/SAR_GuiasTCZ_2011.pdf">http&#58;&#47;&#47;www&#46;reumatologia&#46;org&#46;ar&#47;userfiles&#47;file&#47;publicaciones&#47;revista-reumatologia&#47;SAR&#95;GuiasTCZ&#95;2011&#46;pdf</a> &#91;accessed 04&#46;04&#46;12&#93;&#46;"
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Update on the Brazilian consensus for the diagnosis and treatment of rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;B&#46; Bertolo"
                            1 => "C&#46;V&#46; Brenol"
                            2 => "C&#46;G&#46; Schainberg"
                            3 => "F&#46; Neubarth"
                            4 => "F&#46; de Lima"
                            5 => "I&#46;M&#46; Laurindo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Bras Reumatol"
                        "fecha" => "2007"
                        "volumen" => "47"
                        "paginaInicial" => "151"
                        "paginaFinal" => "159"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gu&#237;a Cl&#237;nica Artritis Reumatoidea"
                      "autores" => array:1 [
                        0 => array:2 [
                          "colaboracion" => "Ministerio de Salud"
                          "etal" => false
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Libro" => array:3 [
                        "fecha" => "2007"
                        "editorial" => "MINSAL"
                        "editorialLocalizacion" => "Santiago"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;www&#46;redsalud&#46;gov&#46;cl&#47;archivos&#47;guiasges&#47;artritispdf&#46;pdf"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gu&#237;as para el tratamiento de la artritis reumatoide"
                      "autores" => array:1 [
                        0 => array:2 [
                          "colaboracion" => "Asociaci&#243;n Colombiana de Reumatolog&#237;a"
                          "etal" => false
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Libro" => array:3 [
                        "fecha" => "2002"
                        "editorial" => "Exlibris Editores SA"
                        "editorialLocalizacion" => "DC Bogota"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dnn&#46;asoreuma&#46;org&#47;Portals&#47;0&#47;Descargas&#47;GUIA&#37;20PARA&#37;20EL&#37;20TRATAMIENTO&#37;20DE&#37;20LA&#37;20AR&#37;20Parte&#37;201&#46;pdf"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gu&#237;as de manejo de la artritis reumatoide Concenso 2010"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Costa Rican Association of Rheumatology"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Acta Med Costarric"
                        "fecha" => "2011"
                        "volumen" => "53"
                        "paginaInicial" => "19"
                        "paginaFinal" => "25"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Colegio Mexicano de Reumatolog&#237;a&#46; Gu&#237;as y recomendaciones del Colegio Mexicano de Reumatolog&#237;a para el uso de agentes biol&#243;gicos en enfermos reum&#225;ticos"
                      "autores" => array:1 [
                        0 => array:2 [
                          "colaboracion" => "Comit&#233; Mexicano del Consenso de Biol&#243;gicos"
                          "etal" => false
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1699-258X(06)73026-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Reumatol Clin"
                        "fecha" => "2006"
                        "volumen" => "2"
                        "paginaInicial" => "78"
                        "paginaFinal" => "89"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21794308"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Instituto Mexicano del Seguro Social&#46; Guia de Referencia Rapida&#58; Diagnostico y Tratamiento de Artritis Rheumatoide del Adulto&#46; IMSS Website&#58; <a class="elsevierStyleInterRef" href="http://www.cvsp.cucs.udg.mx/guias/TODAS/IMSS_195_08_ARTRITIS_REUMATOIDE/IMSS_195_08_GRR.pdf">http&#58;&#47;&#47;www&#46;cvsp&#46;cucs&#46;udg&#46;mx&#47;guias&#47;TODAS&#47;IMSS&#95;195&#95;08&#95;ARTRITIS&#95;REUMATOIDE&#47;IMSS&#95;195&#95;08&#95;GRR&#46;pdf</a> &#91;accessed 04&#46;04&#46;12&#93;&#46;"
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Very recent onset arthritis&#58; the value of initial rheumatologist and anti-cyclic citrullinated peptide antibodies in the diagnosis of rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46; Rojas-Serrano"
                            1 => "R&#46; Burgos-Vargas"
                            2 => "L&#46; Lino Perez"
                            3 => "C&#46;G&#46; Garc&#237;a"
                            4 => "F&#46; Moctezuma"
                            5 => "J&#46; V&#225;zquez-Mellado"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10067-009-1206-z"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Rheumatol"
                        "fecha" => "2009"
                        "volumen" => "28"
                        "paginaInicial" => "1135"
                        "paginaFinal" => "1139"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19504230"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of a treatment strategy of tight control for rheumatoid arthritis &#40;the TICORA study&#41;&#58; a single-blind randomised controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Grigor"
                            1 => "H&#46; Capell"
                            2 => "A&#46; Stirling"
                            3 => "A&#46;D&#46; McMahon"
                            4 => "P&#46; Lock"
                            5 => "R&#46; Vallance"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(04)16676-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2004"
                        "volumen" => "364"
                        "paginaInicial" => "263"
                        "paginaFinal" => "269"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15262104"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Disease activity score-driven therapy versus routine care in patients with recent onset active rheumatoid arthritis&#58; data from the GUEPARD trial and ESPOIR cohort"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Soubrier"
                            1 => "C&#46; Lukas"
                            2 => "J&#46; Sibilia"
                            3 => "B&#46; Fautrel"
                            4 => "F&#46; Roux"
                            5 => "L&#46; Gossec"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2010.137695"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2011"
                        "volumen" => "70"
                        "paginaInicial" => "611"
                        "paginaFinal" => "615"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21242235"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "National Center of Rheumatic Disease &#40;CNER&#41;&#46; Early inflammatory polyarthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Nu&#241;ez-Sotelo"
                            1 => "L&#46;A&#46; Gutierrez-Gonzalez"
                            2 => "N&#46; Gonzalez"
                            3 => "B&#46; Losada"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Med Archiv"
                        "fecha" => "2007"
                        "volumen" => "21"
                        "paginaInicial" => "125"
                        "paginaFinal" => "137"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "EULAR recommendations for the management of early arthritis&#58; report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics &#40;ESCISIT&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46; Combe"
                            1 => "R&#46; Landewe"
                            2 => "C&#46; Lukas"
                            3 => "H&#46;D&#46; Bolosiu"
                            4 => "F&#46; Breedveld"
                            5 => "M&#46; Dougados"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2005.044354"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2007"
                        "volumen" => "66"
                        "paginaInicial" => "34"
                        "paginaFinal" => "45"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16396980"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Registro Panamericano de acontecimientos adversos de terapias biol&#243;gicas en enfermedades reum&#225;ticas&#46; BIOBADASER Website&#58; <a class="elsevierStyleInterRef" href="https://biobadaser.ser.es/biobadamerica/">https&#58;&#47;&#47;biobadaser&#46;ser&#46;es&#47;biobadamerica&#47;</a> &#91;accessed 07&#46;11&#46;11&#93;&#46;"
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active&#44; early&#44; moderate to severe rheumatoid arthritis &#40;COMET&#41;&#58; a randomized&#44; double-blind&#44; parallel treatment trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Emery"
                            1 => "F&#46;C&#46; Breedveld"
                            2 => "S&#46; Hall"
                            3 => "P&#46; Durez"
                            4 => "D&#46;J&#46; Chang"
                            5 => "D&#46; Robertson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(08)61000-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2008"
                        "volumen" => "372"
                        "paginaInicial" => "375"
                        "paginaFinal" => "382"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18635256"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Infliximab in active early rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46;C&#46; Breedveld"
                            1 => "P&#46; Emery"
                            2 => "E&#46; Keystone"
                            3 => "K&#46; Patel"
                            4 => "D&#46;E&#46; Furst"
                            5 => "J&#46;R&#46; Kalden"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2004"
                        "volumen" => "63"
                        "paginaInicial" => "149"
                        "paginaFinal" => "155"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14722203"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The PREMIER study&#58; a multicenter&#44; randomized&#44; double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early&#44; aggressive rheumatoid arthritis who had not had previous methotrexate treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46;C&#46; Breedveld"
                            1 => "M&#46;H&#46; Weisman"
                            2 => "A&#46;F&#46; Kavanaugh"
                            3 => "S&#46;B&#46; Cohen"
                            4 => "K&#46; Pavelka"
                            5 => "R&#46; van Vollenhoven"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.21519"
                      "Revista" => array:7 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2006"
                        "volumen" => "54"
                        "paginaInicial" => "26"
                        "paginaFinal" => "37"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16385520"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0163445312002885"
                          "estado" => "S300"
                          "issn" => "01634453"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis&#58; a six-month&#44; national&#44; multicenter&#44; open-label study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Sellam"
                            1 => "H&#46; Hendel-Chavez"
                            2 => "S&#46; Rouanet"
                            3 => "K&#46; Abbed"
                            4 => "B&#46; Combe"
                            5 => "X&#46; Le Lo&#235;t"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.30233"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2011"
                        "volumen" => "63"
                        "paginaInicial" => "933"
                        "paginaFinal" => "938"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21225699"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition &#91;published correction appears in N Engl J Med 2005&#59;353&#58;2311&#93;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;C&#46; Genovese"
                            1 => "J&#46;C&#46; Becker"
                            2 => "M&#46; Schiff"
                            3 => "M&#46; Luggen"
                            4 => "Y&#46; Sherrer"
                            5 => "J&#46; Kremer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa050524"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2005"
                        "volumen" => "353"
                        "paginaInicial" => "1114"
                        "paginaFinal" => "1123"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16162882"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals&#58; results from a 24-week multicentre randomised placebo-controlled trial &#91;published correction appears in Ann Rheum Dis 2009&#59;68&#58;296&#93;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Emery"
                            1 => "E&#46; Keystone"
                            2 => "H&#46;P&#46; Tony"
                            3 => "A&#46; Cantagre"
                            4 => "R&#46; van Vollenhoven"
                            5 => "A&#46; Sanchez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2008.092932"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2008"
                        "volumen" => "67"
                        "paginaInicial" => "1516"
                        "paginaFinal" => "1523"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18625622"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Emerging therapeutics for rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "C&#46;O&#46; Bingham III"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Bull NYU Hosp Jt Dis"
                        "fecha" => "2008"
                        "volumen" => "66"
                        "paginaInicial" => "210"
                        "paginaFinal" => "215"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18937634"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "New and emerging therapies for the treatment of rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "M&#46;G&#46; Feely"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Open Access Rheumatol Res Rev"
                        "fecha" => "2010"
                        "volumen" => "2"
                        "paginaInicial" => "35"
                        "paginaFinal" => "43"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tofacitinib &#40;CP-690&#44;550&#41;&#44; an oral janus kinase inhibitor&#44; or adalimumab versus placebo in patients with rheumatoid arthritis on background methotrexate&#58; a phase 3 study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; van Vollenhoven"
                            1 => "R&#46; Fleischmann"
                            2 => "S&#46; Cohen"
                            3 => "E&#46;B&#46; Lee"
                            4 => "G&#46; Meijide"
                            5 => "S&#46; Wagner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2011"
                        "volumen" => "63"
                        "paginaInicial" => "S153"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An oral spleen tyrosine kinase &#40;SyK&#41; inhibitor for rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46;E&#46; Weiblatt"
                            1 => "A&#46; Kavanaugh"
                            2 => "M&#46;C&#46; Genovese"
                            3 => "T&#46;K&#46; Musser"
                            4 => "E&#46;B&#46; Grossbard"
                            5 => "D&#46;B&#46; Magilavy"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1000500"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2010"
                        "volumen" => "363"
                        "paginaInicial" => "1303"
                        "paginaFinal" => "1312"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20879879"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor &#945; inhibitors &#40;GO-AFTER study&#41;&#58; a multicenter&#44; randomized&#44; double-blind&#44; placebo-controlled&#44; phase III trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;S&#46; Smolen"
                            1 => "J&#46; Kay"
                            2 => "M&#46;K&#46; Doyle"
                            3 => "R&#46; Landew&#233;"
                            4 => "E&#46;L&#46; Matteson"
                            5 => "J&#46; Wollenhaupt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(09)60506-7"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2009"
                        "volumen" => "374"
                        "paginaInicial" => "210"
                        "paginaFinal" => "221"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19560810"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis&#58; the RAPID 2 study&#46; A randomized&#44; controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Smolen"
                            1 => "R&#46;B&#46; Landewe"
                            2 => "P&#46; Mease"
                            3 => "J&#46; Brzezicki"
                            4 => "D&#46; Mason"
                            5 => "K&#46; Luijtens"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2008.101659"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2009"
                        "volumen" => "68"
                        "paginaInicial" => "797"
                        "paginaFinal" => "804"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19015207"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biosimilars&#58; the debate continues"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46;A&#46; Colbert"
                            1 => "B&#46;N&#46; Cronstein"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.30505"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2011"
                        "volumen" => "63"
                        "paginaInicial" => "2848"
                        "paginaFinal" => "2850"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21702015"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Scientific and legal viability of follow-on protein drugs"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "D&#46;M&#46; Dudzinski"
                            1 => "A&#46;S&#46; Kesselheim"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMhle0706973"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2008"
                        "volumen" => "358"
                        "paginaInicial" => "843"
                        "paginaFinal" => "849"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18287608"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biosimilars&#58; a regulatory perspective from America"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46; Kay"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/ar3310"
                      "Revista" => array:5 [
                        "tituloSerie" => "Arthritis Res Ther"
                        "fecha" => "2011"
                        "volumen" => "13"
                        "paginaInicial" => "112"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21586106"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biosimilars of biological drugs therapies&#44; regulatory&#44; clinical and commercial considerations"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "G&#46; Dranitsaris"
                            1 => "E&#46; Amir"
                            2 => "K&#46; Dorward"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2165/11593730-000000000-00000"
                      "Revista" => array:6 [
                        "tituloSerie" => "Drugs"
                        "fecha" => "2011"
                        "volumen" => "71"
                        "paginaInicial" => "1527"
                        "paginaFinal" => "1536"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21861538"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mexico recovers leadership on regulation of biosimilar biotech drugs"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "C&#46; L&#243;pez-Silva"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Gac Med Mex"
                        "fecha" => "2012"
                        "volumen" => "148"
                        "paginaInicial" => "83"
                        "paginaFinal" => "90"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22367313"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Etanar therapy in real-life patients with rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Rondon"
                            1 => "A&#46; Bautista"
                            2 => "J&#46;C&#46; Salazar"
                            3 => "N&#46; Casas"
                            4 => "P&#46; Santos"
                            5 => "F&#46; Vargas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2010"
                        "volumen" => "62"
                        "numero" => "Suppl&#46; 10"
                        "paginaInicial" => "1811"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Dr Reddy&#39;s brand of rituximab&#46; Dr Reddy&#39;s Laboratories Inc&#46; Website&#58; <a class="elsevierStyleInterRef" href="http://www.drreddys.com/products/pdf/bio/Reditux-splash.pdf">http&#58;&#47;&#47;www&#46;drreddys&#46;com&#47;products&#47;pdf&#47;bio&#47;Reditux-splash&#46;pdf</a> &#91;accessed 04&#46;04&#46;12&#93;&#46;"
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "TL011 in Severe&#44; Active Rheumatoid Arthritis Patients&#46; Clinical Trials Website&#58; <a class="elsevierStyleInterRef" href="http://www.clinicaltrials.gov/ct2/show/NCT01123070%3Fterm=TEVA%26cond=arthritis%26rank=2">http&#58;&#47;&#47;www&#46;clinicaltrials&#46;gov&#47;ct2&#47;show&#47;NCT01123070&#63;term&#61;TEVA&#38;cond&#61;arthritis&#38;rank&#61;2</a>&#46; Accessed February 7&#44; 2012&#46;"
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Yisaipu Website&#58; <a class="elsevierStyleInterRef" href="http://www.yisaipu.com/DiseaseList.aspx%3Fcate_id=20%26topCateID1=20%26topCateID=15">http&#58;&#47;&#47;www&#46;yisaipu&#46;com&#47;DiseaseList&#46;aspx&#63;cate&#95;id&#61;20&#8868;CateID1&#61;20&#8868;CateID&#61;15</a> &#91;accessed 22&#46;08&#46;12&#93;&#46;"
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "PRX-106&#46; Protalix Biotherapeutics Website&#58; <a class="elsevierStyleInterRef" href="http://www.protalix.com/product-development/prx-106.asp">http&#58;&#47;&#47;www&#46;protalix&#46;com&#47;product-development&#47;prx-106&#46;asp</a> &#91;accessed 04&#46;04&#46;12&#93;&#46;"
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Pipelines&#46; LG Life Sciences Website&#58; <a class="elsevierStyleInterRef" href="http://www.lgls.com/rd/pipeline.jsp">http&#58;&#47;&#47;www&#46;lgls&#46;com&#47;rd&#47;pipeline&#46;jsp</a> &#91;accessed 04&#46;04&#46;12&#93;&#46;"
                ]
              ]
            ]
          ]
        ]
      ]
    ]
    "agradecimientos" => array:1 [
      0 => array:3 [
        "identificador" => "xack34611"
        "titulo" => "Acknowledgments"
        "texto" => "<p id="par0190" class="elsevierStylePara elsevierViewall">Editorial&#47;medical writing support was provided by WC Hatch at ACUMED and was funded by <span class="elsevierStyleGrantSponsor">Pfizer Inc</span>&#46; No financial support was provided to the authors for this work&#46;</p>"
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/21735743/0000000900000002/v1_201304200246/S2173574313000130/v1_201304200246/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "8383"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Review Article"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/21735743/0000000900000002/v1_201304200246/S2173574313000130/v1_201304200246/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574313000130?idApp=UINPBA00004M"
]

Article information

ISSN: 21735743
Original language: English

DOI:10.1016/j.reumae.2013.01.007

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	12	11	23
2024 October	89	37	126
2024 September	59	36	95
2024 August	79	49	128
2024 July	84	50	134
2024 June	85	46	131
2024 May	99	50	149
2024 April	85	37	122
2024 March	57	34	91
2024 February	57	38	95
2024 January	44	27	71
2023 December	49	34	83
2023 November	58	36	94
2023 October	145	51	196
2023 September	130	50	180
2023 August	33	35	68
2023 July	53	45	98
2023 June	26	40	66
2023 May	19	9	28
2023 April	29	17	46
2023 March	102	26	128
2023 February	69	37	106
2023 January	53	19	72
2022 December	93	39	132
2022 November	99	33	132
2022 October	73	45	118
2022 September	79	43	122
2022 August	70	37	107
2022 July	47	80	127
2022 June	52	49	101
2022 May	52	50	102
2022 April	63	51	114
2022 March	58	40	98
2022 February	61	46	107
2022 January	59	32	91
2021 December	38	45	83
2021 November	36	48	84
2021 October	57	56	113
2021 September	38	51	89
2021 August	36	33	69
2021 July	37	28	65
2021 June	51	38	89
2021 May	51	25	76
2021 April	105	64	169
2021 March	60	60	120
2021 February	59	26	85
2021 January	69	34	103
2020 December	46	30	76
2020 November	50	22	72
2020 October	41	13	54
2020 September	51	24	75
2020 August	49	22	71
2020 July	50	23	73
2020 June	41	28	69
2020 May	40	19	59
2020 April	60	25	85
2020 March	17	13	30
2020 February	2	0	2
2019 January	1	0	1
2018 May	7	2	9
2018 April	64	13	77
2018 March	74	14	88
2018 February	31	18	49
2018 January	38	16	54
2017 December	44	13	57
2017 November	61	16	77
2017 October	64	13	77
2017 September	42	15	57
2017 August	43	19	62
2017 July	48	20	68
2017 June	60	23	83
2017 May	64	37	101
2017 April	46	14	60
2017 March	62	27	89
2017 February	47	29	76
2017 January	59	31	90
2016 December	86	36	122
2016 November	69	15	84
2016 October	120	21	141
2016 September	120	35	155
2016 August	100	28	128
2016 July	52	28	80
2016 May	1	0	1
2016 February	1	0	1
2016 January	5	21	26
2015 December	2	0	2
2015 November	1	27	28
2015 October	5	0	5
2015 September	1	0	1
2015 August	2	19	21
2015 July	64	7	71
2015 June	99	26	125
2015 May	89	30	119
2015 April	58	42	100
2015 March	79	33	112
2015 February	63	11	74
2015 January	80	19	99
2014 December	75	16	91
2014 November	83	18	101
2014 October	122	28	150
2014 September	62	10	72
2014 August	48	11	59
2014 July	46	17	63
2014 June	79	10	89
2014 May	59	20	79
2014 April	67	12	79
2014 March	66	19	85
2014 February	48	12	60
2014 January	91	11	102
2013 December	47	10	57
2013 November	41	11	52
2013 October	64	13	77
2013 September	54	11	65
2013 August	56	14	70
2013 July	32	5	37
2013 June	51	14	65
2013 May	44	32	76
2013 April	24	15	39

Show all

Indexed in:

Follow us:

Subscribe:

Statistics

Indexed in:

Follow us:

Subscribe:

Statistics

Subscribe to our newsletter