Brief Report
VARIAR Study: Assessment of Short-term Efficacy and Safety of Rituximab Compared to an Tumor Necrosis Factor Alpha Antagonists as Second-line Drug Therapy in Patients With Rheumatoid Arthritis Refractory to a First Tumor Necrosis Factor Alpha Antagonist
Estudio VARIAR: VAloración de la eficacia y seguridad a corto plazo en artritis reumatoide del uso de RItuximab comparado con Antagonistas del factor de necrosis tumoral alfa en segunda línea terapéutica en pacientes con artritis reumatoide Refractarios a un primer antagonista del factor de necrosis tumoral alfa
Vicenç Torrente-Segarraa,
, Asunción Acosta Pereirab, Rosa Morlac, José Miguel Ruizd, Teresa Clavaguerae, Ramon Figulsa, Hector Corominasa, Carme Gelib, Rosa Rosellóf, Juan José de Agustíng, Cayetano Alegreg, Carolina Pérezh, Angel Garcíai, Arturo Rodríguez de la Sernab
Corresponding author
a Hospital General Hospitalet-Moisès Broggi, Sant Joan Despí, Barcelona, Spain
b Hospital Santa Creu i Sant Pau, Barcelona, Spain
c Hospital del Vendrell, El Vendrell, Tarragona, Spain
d Hospital de Viladecans, Viladecans, Barcelona, Spain
e Hospital de Palamós, Palamós, Girona, Spain
f Hospital de San Jorge, Huesca, Spain
g Hospital de la Vall d’Hebron, Barcelona, Spain
h Hospital de Mollet, Mollet del Vallès, Barcelona, Spain
i Hospital de Torrevieja, Torrevieja, Alicante, Spain
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=> array:2 [ "etiqueta" => "<span class="elsevierStyleSup">i</span>" "identificador" => "aff0045" ] ] ] 13 => array:3 [ "nombre" => "Arturo" "apellidos" => "Rodríguez de la Serna" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:9 [ 0 => array:3 [ "entidad" => "Hospital General Hospitalet-Moisès Broggi, Sant Joan Despí, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Hospital Santa Creu i Sant Pau, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Hospital del Vendrell, El Vendrell, Tarragona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Hospital de Viladecans, Viladecans, Barcelona, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Hospital de Palamós, Palamós, Girona, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Hospital de San Jorge, Huesca, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Hospital de la Vall d’Hebron, Barcelona, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Hospital de Mollet, Mollet del Vallès, Barcelona, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Hospital de Torrevieja, Torrevieja, Alicante, Spain" "etiqueta" => "i" "identificador" => "aff0045" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Estudio VARIAR: VAloración de la eficacia y seguridad a corto plazo en artritis reumatoide del uso de RItuximab comparado con Antagonistas del factor de necrosis tumoral alfa en segunda línea terapéutica en pacientes con artritis reumatoide Refractarios a un primer antagonista del factor de necrosis tumoral alfa" ] ] "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" => 1123 "Ancho" => 1635 "Tamanyo" => 94928 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">EULAR response rate after 6 months. No significant differences (<span class="elsevierStyleItalic">P</span>>.05) between the 2 groups. EULAR, European League Against Rheumatism.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Rheumatoid arthritis (RA) is an inflammatory, autoimmune disease, that affects the Spanish population with a prevalence estimated to be 0.5%, and is more common in women than in men. It is a chronic disabling disease with several social and economic costs and a considerable psychological impact, in addition to the substantial decrease in quality of life related to the health of these patients.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> The treatment of RA, since the development of biologic disease-modifying drugs, has advanced in terms of controlling the disease, improving the symptoms and the progression of joint damage, with a good safety profile.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Given the first appearance of anti-tumor necrosis factor (TNF) agents as a biological therapy (BT), they have been the most widely utilized approach. The recommendations of the Spanish Society of Rheumatology<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a> endorse both the possible change in therapeutic target, as well as the replacement of an anti-TNF agent for another. It could be that there are patients for whom a change in therapeutic target is more interesting than changing from a TNFα inhibitor over the successive therapeutic lines.</p><p id="par0015" class="elsevierStylePara elsevierViewall">There are data in the scientific literature that support both the change (switching) of an anti-TNF by another, consecutively, as well as a change in the therapeutic target, with rituximab, among others, even making known their preference for the latter among seropositive patients.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">4–8</span></a> Some of these results come from large observational registries, but not from prospective studies.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The objective of our report is to evaluate the clinical efficacy and safety 6 months after beginning treatment with rituximab, compared to a second anti-TNF in the second BT line among patients with a diagnosis of RA, in clinical practice.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients, Material and Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">This is a prospective observational study in the clinical practice setting, that was postauthorized for clinical practice in patients with severe RA (1987 American Rheumatism Association criteria<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a>) being treated with a second line of BT, after having an inappropriate response or intolerance to a first anti-TNF agent. The study was approved by the ethics committee of each participating center, and the patients gave their informed consent. A total of 9 Spanish centers at the national level and 14 rheumatologists participated in the study, which covered the period from June 2009 to September 2011.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The patients were recruited consecutively and received either a second anti-TNF (2TNF), or rituximab (RTX), depending on the judgment of each researcher and in accordance with the recommendations of the Guidelines concerning the use of biological therapy provided by the Spanish Society of Rheumatology.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Baseline variables and 6 months later (prior to beginning the second cycle of RTX administration):<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0040" class="elsevierStylePara elsevierViewall">Age, sex, duration of the disease, cause for discontinuing the first anti-TNF (primary or secondary, intolerance/adverse effect).</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0045" class="elsevierStylePara elsevierViewall">Tender joint count (TJC), swollen joint count (SJC).</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0050" class="elsevierStylePara elsevierViewall">Erythrocyte sedimentation rate (ESR) in mmHg, C-reactive protein (CRP) in mg/dL, positive IgM rheumatoid factor (RF) (if titer >15<span class="elsevierStyleHsp" style=""></span>U/mL) and titer by nephelometry, positive anti-citrullinated protein antibodies, if titer >20<span class="elsevierStyleHsp" style=""></span>U/mL, by means of enzyme immunoassay.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">Disease Activity Score in 28 joints (DAS28) of 3 variables including ESR.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a></p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">Mild adverse effect: does not require hospital admission, is treated by discontinuing the drug; severe adverse effect: requires hospital admission and specific treatment.</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0065" class="elsevierStylePara elsevierViewall">Questionnaire in Spanish validated by the Health Assessment Questionnaire (HAQ).<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a></p></li></ul></p><p id="par0070" class="elsevierStylePara elsevierViewall">The purpose was to compare the clinical effects of RTX and those of a 2TNF as a second line of BT in RA patients 6 months, after a good/moderate European League Against Rheumatism (EULAR) response,<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> using improvements in ESR, CRP, RF and HAQ. We also evaluated the percentage of patients who request switching the drug because of an adverse effect.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical Analysis</span><p id="par0075" class="elsevierStylePara elsevierViewall">The statistical analysis will be based on the data introduced into the database, with a descriptive analysis of all the categorical and continuous variables.</p><p id="par0080" class="elsevierStylePara elsevierViewall">To make comparisons over the study period, in the case of continuous variables, the Snedecor F test (ANOVA) is used, if the variables are normally distributed, or the Friedman test if they do not meet parametric criteria. In the case of dichotomous variables, the Cochran test should be utilized.</p><p id="par0085" class="elsevierStylePara elsevierViewall">The value of the statistical significance is established at <span class="elsevierStyleItalic">P</span><.05. All the analyses are done with the SPSS 19.0 software package.</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0090" class="elsevierStylePara elsevierViewall">We included a total of 103 patients, 54 in the RTX group and 49 in the group for 2TNF (23 etanercept [47%], 16 adalimumab [32%] and 10 infliximab [20%]); the major sociodemographic and clinical variables of the latter are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">The changes in the clinical, serological and functional parameters are represented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. There was a significant reduction in all the clinical, serological and functional variables at 6 months, that was greater in terms of percentage points in the RTX group. These differences were not significant, except with regard to the reduction of ESR levels (greater in the RTX group [<span class="elsevierStyleItalic">P</span>=.023]). The EULAR response rates are shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">A total of 21 patients requested discontinuation of their treatment (11 in the RTX group and 10 from the 2TNF group). In all, 3 patients (27%) in the RTX group did not complete the 6-month evaluation because they had experienced a mild adverse effect, as did another 3 (30%) in the 2TNF group, without evident statistically significant differences (<span class="elsevierStyleItalic">P</span>=.457). There were no severe adverse effects in any group. The rest of the patients were excluded from the study due to the presence of a decline or persistence of symptoms that meant a change in the therapeutic strategy on the part of the rheumatologist in 73% in the RTX group and 70% in the 2TNF group.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0105" class="elsevierStylePara elsevierViewall">This is a prospective clinical practice study, that compares the short-term efficacy of RTX with an anti-TNF in a second BT line after a failure in an anti-TNF in patients with RA.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Overall, the efficacy of RTX was good, with an elevated proportion of patients with a good/moderate EULAR response (64%), comparable to the 59% of 2TNF, even after receiving only a single cycle of RTX, as the evaluation of the clinical efficacy was performed prior to the primary administration of the second cycle corresponding to the 6 months. Moreover, the population who received RTX had a higher activity level according to the DAS28 score, even higher than that of the comparative group (5.45 vs 5.18, respectively). It is important to point out that the majority of these patients discontinued their previous anti-TNF due to a primary inefficacy, something that suggests previous observations.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Although we found no significant clinical or functional differences, we can observe that RTX shows, as least, the same efficacy as a 2TNF in clinical practice, in a short follow-up time (6 months). At the biological level, we did encounter a higher reduction of the ESR levels in the RTX group, very similar to findings published by Finckh et al.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> This group found greater differences in efficacy in patients treated with RTX in a second BT line than those treated with 2TNF, with a sample size very similar to that of our study, something that was also reported in subsequent explorations.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> These observations were also examined in our population by Gomez-Reino et al.,<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> in an observational study at 6, 9 and 12 months in patients with a failure of 1 or more anti-TNF, and those authors found significant differences between the 2 therapeutic strategies. In any case, this last study did find differences in the reduction in DAS28 in those patients who had been previously treated with infliximab and adalimumab. In a later study, the response was evaluated at the radiographic level, and there were no differences between the use of RTX or an 2TNF after the failure of an anti-TNF.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">The limitations of our study are, mainly, the size of the sample (which limits its analysis by subgroups), the higher baseline activity in the RTX group, the design in the clinical setting, the follow-up period and the absence of radiologic evaluations. However, on the other hand, the prospective nature grants our findings greater value than that of other reports published in this same line.</p><p id="par0125" class="elsevierStylePara elsevierViewall">In conclusion, our data demonstrate that, in a second BT line, after the failure of a primary anti-TNF utilized in the clinical setting, RTX can be, at least, as useful as a second anti-TNF.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Ethical Disclosures</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Protection of human and animal subjects</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors declare that the procedures followed were in accordance with the regulations of the relevant clinical research ethics committee and with those of the Code of Ethics of the World Medical Association (Declaration of Helsinki).</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Confidentiality of data</span><p id="par0135" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Right to privacy and informed consent</span><p id="par0140" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicts of Interest</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors declare they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres752409" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec754799" "titulo" => "Keyword" ] 2 => array:3 [ "identificador" => "xres752408" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec754800" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients, Material and Methods" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Statistical Analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 8 => array:3 [ "identificador" => "sec0030" "titulo" => "Ethical Disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflicts of Interest" ] 10 => array:2 [ "identificador" => "xack250151" "titulo" => "Acknowledgements" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-07-06" "fechaAceptado" => "2015-11-25" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keyword" "identificador" => "xpalclavsec754799" "palabras" => array:3 [ 0 => "Rheumatoid arthritis" 1 => "Rituximab" 2 => "Anti-TNF-alpha" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec754800" "palabras" => array:3 [ 0 => "Artritis reumatoide" 1 => "Rituximab" 2 => "Anti-TNF-alfa" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To compare the short-term efficacy and safety of rituximab (RTX) therapy versus anti-TNF in rheumatoid arthritis (RA) patients after discontinuation of a first anti-TNF agent.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Prospective observational multicenter study in the clinical practice setting, involving patients with severe RA refractory to a first anti-TNF agent, who received either RTX or a second anti-TNF (2TNF), comparing the efficacy endpoints, EULAR response (Good/Moderate) and safety at 6 months.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">103 patients enrolled, 82 completed 6-month follow-up, 73.7% women. Baseline data for RTX and 2TNF groups, respectively: TJC, 8.6 and 6.6; SJC, 8.8 and 7.5; DAS28 score, 5.45 (±1.28) and 5.18 (±1.21) (<span class="elsevierStyleItalic">P</span>=.048), ESR, 41 and 38.7<span class="elsevierStyleHsp" style=""></span>mmHg; and HAQ, 1.2 and 1.0. Improvement was observed in all parameters, with no significant differences (except for a more marked reduction in ESR with RTX). There were no serious adverse events.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">RTX use as second-line therapy after anti-TNF failure led to improvements in the efficacy and functional variables at 6 months, with no serious adverse events. These results were comparable to those observed in patients who used a second anti-TNF agent in the same clinical scenario.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evaluar la eficacia y la seguridad a corto plazo del tratamiento de pacientes con artritis reumatoide (AR) con rituximab (RTX) comparado con un anti-TNF (2TNF) tras retirada de un primer anti-TNF.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio multicéntrico prospectivo, observacional, de práctica clínica de pacientes con AR grave refractaria a anti-TNF que recibieron RTX comparados con los que recibieron un 2TNF. Comparación de las variables de eficacia y respuesta EULAR buena/moderada a los 6 meses.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Ciento tres pacientes incluidos; 82 alcanzan seguimiento a 6 meses, 73,7% mujeres. Datos basales grupo RTX y 2TNF, respectivamente: 8,6 y 6,6 NAD, 8,8 y 7,5 NAI, 5,45 ± 1,28 y 5,18 ± 1,21 en DAS28 (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,048), 41 y 38,7<span class="elsevierStyleHsp" style=""></span>mmHg de VSG, y 1,2 y 1,0 en HAQ. Mejoría en todos los parámetros en ambos grupos sin diferencias significativas (excepto mayor reducción de VSG con RTX). Ausencia de efectos adversos graves.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El uso de RTX en segunda línea de terapia biológica tras fallo a un primer anti-TNF en práctica clínica muestra mejoría en las variables de eficacia y funcionalidad a los 6 meses, sin presentar efectos adversos graves. Estos resultados no difieren de los observados tras el uso de un segundo anti-TNF en el mismo escenario clínico.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as: Torrente-Segarra V, Acosta Pereira A, Morla R, Ruiz JM, Clavaguera T, Figuls R, et al. Estudio VARIAR: VAloración de la eficacia y seguridad a corto plazo en artritis reumatoide del uso de RItuximab comparado con Antagonistas del factor de necrosis tumoral alfa en segunda línea terapéutica en pacientes con artritis reumatoide Refractarios a un primer antagonista del factor de necrosis tumoral alfa. Reumatol Clin. 2016;12:319–322.</p>" ] ] "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" => 1123 "Ancho" => 1635 "Tamanyo" => 94928 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">EULAR response rate after 6 months. No significant differences (<span class="elsevierStyleItalic">P</span>>.05) between the 2 groups. EULAR, European League Against Rheumatism.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Results expressed as mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>standard deviation and percentages.</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">ACPA, anti-citrullinated protein antibodies; CRP, C-reactive protein; DAS28, Disease Activity Score 28 joints; ESR, erythrocyte sedimentation rate; HAQ, Health Assessment Questionnaire; RA, rheumatoid arthritis; SJC, swollen joint count; TJC, tender joint count; TNF, anti-tumor necrosis factor α.</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"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">Rituximab</span> (<span class="elsevierStyleItalic">n</span>=54) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">2 TNF</span> (<span class="elsevierStyleItalic">n</span>=49) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">Total</span> (<span class="elsevierStyleItalic">n</span>=103) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Age (years)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">58.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">57.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>13.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Gender (female, %)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">77.7% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">67.3% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">73.7% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Duration of RA (years)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">DAS28</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.45<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.5<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.18<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.8<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.37<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">HAQ</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">TJC</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">SJC</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">ESR (mmHg)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">41.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>24.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">38.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>22.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>26.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">CRP (mg/dL)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">27.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>18.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Rheumatoid factor</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Titer (U/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>80.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">82.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>64.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">91.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>73.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>% (positive) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70.2% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">75.7% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">72.8% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">ACPA (positive)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50.2% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">53.1% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">51.4% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Previous TNF</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Etanercept \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">32% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">33% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Infliximab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Adalimumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">44% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">46% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">41% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Reason for discontinuing previous TNF</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>-Primary inefficacy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">93% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">94% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">93% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Secondary inefficacy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Adverse effect and/or intolerance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Concomitant use of methotrexate</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">92.5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">77.5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">87.3% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1245364.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">No significant differences (<span class="elsevierStyleItalic">P</span>>.5) between all the variables of the different groups, except in baseline DAS28 score (<span class="elsevierStyleItalic">P</span>=.048), which was higher in the group that received rituximab.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Baseline Sociodemographic and Clinical Variables.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Results expressed as mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>standard deviation and percentages.</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">CRP, C-reactive protein; DAS28, Disease Activity Score 28 joints; ESR, erythrocyte sedimentation rate; HAQ, Health Assessment Questionnaire; RTX, rituximab; SJC, swollen joint count; TJC, tender joint count; TNF, anti-tumor necrosis factor.</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"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">RTX \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2 TNF \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">TJC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.431 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">SJC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.387 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">DAS28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.76<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.298 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">ESR (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>17.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.023<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">CRP (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.333 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">HAQ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.82<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.59<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.69 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.960 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1245363.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0010"><span class="elsevierStyleItalic">P</span><.05.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Changes in the Clinical and Serological Parameters at 6 Months.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The prevalence of rheumatoid arthritis in the general population of Spain" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "EPISER StudyGroup" "etal" => false "autores" => array:6 [ 0 => "L. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 12 | 17 |
| 2024 October | 71 | 38 | 109 |
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| 2024 January | 28 | 15 | 43 |
| 2023 December | 32 | 28 | 60 |
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| 2023 September | 86 | 40 | 126 |
| 2023 August | 31 | 12 | 43 |
| 2023 July | 32 | 24 | 56 |
| 2023 June | 36 | 24 | 60 |
| 2023 May | 55 | 22 | 77 |
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| 2023 March | 80 | 30 | 110 |
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| 2022 December | 81 | 43 | 124 |
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| 2022 January | 33 | 36 | 69 |
| 2021 December | 34 | 44 | 78 |
| 2021 November | 42 | 33 | 75 |
| 2021 October | 70 | 58 | 128 |
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| 2021 March | 38 | 24 | 62 |
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| 2020 December | 39 | 24 | 63 |
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| 2020 April | 28 | 24 | 52 |
| 2020 March | 17 | 5 | 22 |
| 2020 February | 1 | 0 | 1 |
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| 2018 May | 4 | 1 | 5 |
| 2018 April | 41 | 9 | 50 |
| 2018 March | 118 | 12 | 130 |
| 2018 February | 24 | 8 | 32 |
| 2018 January | 16 | 3 | 19 |
| 2017 December | 31 | 9 | 40 |
| 2017 November | 27 | 10 | 37 |
| 2017 October | 31 | 7 | 38 |
| 2017 September | 26 | 10 | 36 |
| 2017 August | 28 | 14 | 42 |
| 2017 July | 41 | 20 | 61 |
| 2017 June | 40 | 19 | 59 |
| 2017 May | 43 | 24 | 67 |
| 2017 April | 30 | 17 | 47 |
| 2017 March | 32 | 41 | 73 |
| 2017 February | 17 | 13 | 30 |
| 2017 January | 54 | 39 | 93 |
| 2016 December | 58 | 47 | 105 |
| 2016 November | 41 | 43 | 84 |
| 2016 October | 5 | 5 | 10 |
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