Letter to the Editor
Treatment With Monoclonal Antibodies and Pregnancy in Women With Systemic Inflammatory Diseases: A Special Situation
Una situación especial: tratamiento con anticuerpos monoclonales y embarazo en mujeres con enfermedades inflamatorias sistémicas
Read
13608
Timeswas read the article
2220
Total PDF
11388
Total HTML
Share statistics
array:23 [ "pii" => "S2173574316300910" "issn" => "21735743" "doi" => "10.1016/j.reumae.2016.01.004" "estado" => "S300" "fechaPublicacion" => "2016-11-01" "aid" => "879" "copyrightAnyo" => "2016" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Reumatol Clin. 2016;12:359-60" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1281 "formatos" => array:3 [ "EPUB" => 57 "HTML" => 974 "PDF" => 250 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S1699258X16000115" "issn" => "1699258X" "doi" => "10.1016/j.reuma.2016.01.006" "estado" => "S300" "fechaPublicacion" => "2016-11-01" "aid" => "879" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Reumatol Clin. 2016;12:359-60" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 5553 "formatos" => array:3 [ "EPUB" => 191 "HTML" => 4115 "PDF" => 1247 ] ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta al Editor</span>" "titulo" => "Una situación especial: tratamiento con anticuerpos monoclonales y embarazo en mujeres con enfermedades inflamatorias sistémicas" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "359" "paginaFinal" => "360" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Treatment with monoclonal antibodies and pregnancy in women with systemic inflammatory diseases: A special situation" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1504 "Ancho" => 2480 "Tamanyo" => 176624 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">La inmunoglobulina G cruza la barrera placentaria gracias al sistema transportador FcRN, presente en las células del sincitiotrofoblasto.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Fab: región variable; Fc: región constante de la inmunoglobulina; FcRN: receptor Fc neonatal.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Lara Valor, Juan Gabriel Ovalles-Bonilla, Diana Hernández-Flórez, Francisco Javier López-Longo" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Lara" "apellidos" => "Valor" ] 1 => array:2 [ "nombre" => "Juan Gabriel" "apellidos" => "Ovalles-Bonilla" ] 2 => array:2 [ "nombre" => "Diana" "apellidos" => "Hernández-Flórez" ] 3 => array:2 [ "nombre" => "Francisco Javier" "apellidos" => "López-Longo" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173574316300910" "doi" => "10.1016/j.reumae.2016.01.004" "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/S2173574316300910?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X16000115?idApp=UINPBA00004M" "url" => "/1699258X/0000001200000006/v1_201610280501/S1699258X16000115/v1_201610280501/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2173574316300909" "issn" => "21735743" "doi" => "10.1016/j.reumae.2016.01.003" "estado" => "S300" "fechaPublicacion" => "2016-11-01" "aid" => "876" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Reumatol Clin. 2016;12:360-2" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1088 "formatos" => array:3 [ "EPUB" => 59 "HTML" => 777 "PDF" => 252 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Polymyositis in a Patient With Ulcerative Colitis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "360" "paginaFinal" => "362" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Polimiositis en un paciente con colitis ulcerosa" ] ] "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" => 2102 "Ancho" => 2833 "Tamanyo" => 1020836 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Image of the muscle biopsy: (A) There are muscle fibers with regenerative peripheral basophilic areas (hematoxylin–eosin stain ×63). (B) Muscle expression of the class I antigens of the human leukocyte antigen (HLA) system. (C) There is an endomysial lymphocyte cell infiltrate located in the (hematoxylin–eosin stain ×40). (D) Variability of the size of the muscle fibers and periendomysial (hematoxylin–eosin stain ×10).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Andrés González García, Walter Alberto Sifuentes-Giraldo, Sergio Diz Fariña, Héctor Pian" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Andrés" "apellidos" => "González García" ] 1 => array:2 [ "nombre" => "Walter Alberto" "apellidos" => "Sifuentes-Giraldo" ] 2 => array:2 [ "nombre" => "Sergio" "apellidos" => "Diz Fariña" ] 3 => array:2 [ "nombre" => "Héctor" "apellidos" => "Pian" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1699258X16000085" "doi" => "10.1016/j.reuma.2016.01.003" "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/S1699258X16000085?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574316300909?idApp=UINPBA00004M" "url" => "/21735743/0000001200000006/v1_201611050033/S2173574316300909/v1_201611050033/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2173574316300922" "issn" => "21735743" "doi" => "10.1016/j.reumae.2016.01.005" "estado" => "S300" "fechaPublicacion" => "2016-11-01" "aid" => "881" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Reumatol Clin. 2016;12:358-9" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1391 "formatos" => array:3 [ "EPUB" => 52 "HTML" => 975 "PDF" => 364 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "New Drugs in Takayasu Arteritis, Role of Tocilizumab" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "358" "paginaFinal" => "359" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Nuevos fármacos en la arteritis de Takayasu, papel del tocilizumab" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Sonia Martín Guillén, Antonio Álvarez de Cienfuegos, Roberto Hurtado García" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Sonia" "apellidos" => "Martín Guillén" ] 1 => array:2 [ "nombre" => "Antonio" "apellidos" => "Álvarez de Cienfuegos" ] 2 => array:2 [ "nombre" => "Roberto" "apellidos" => "Hurtado García" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1699258X16000292" "doi" => "10.1016/j.reuma.2016.01.008" "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/S1699258X16000292?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574316300922?idApp=UINPBA00004M" "url" => "/21735743/0000001200000006/v1_201611050033/S2173574316300922/v1_201611050033/en/main.assets" ] "en" => array:16 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Treatment With Monoclonal Antibodies and Pregnancy in Women With Systemic Inflammatory Diseases: A Special Situation" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">Dear Editor</span>:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "359" "paginaFinal" => "360" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Lara Valor, Juan Gabriel Ovalles-Bonilla, Diana Hernández-Flórez, Francisco Javier López-Longo" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Lara" "apellidos" => "Valor" "email" => array:1 [ 0 => "lvalor.hgugm@salud.madrid.org" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Juan Gabriel" "apellidos" => "Ovalles-Bonilla" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Diana" "apellidos" => "Hernández-Flórez" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Francisco Javier" "apellidos" => "López-Longo" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital General Universitario Gregorio Marañón, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Instituto de Investigación Biomédica del Hospital Gregorio Marañón, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Una situación especial: tratamiento con anticuerpos monoclonales y embarazo en mujeres con enfermedades inflamatorias sistémicas" ] ] "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" => 1440 "Ancho" => 2444 "Tamanyo" => 166803 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Immunoglobulin G crosses the placental barrier through the FcRn transport system, present in the syncytiotrophoblast cells. Fab, variable region; Fc, constant region of the immunoglobulin; FcRn, neonatal Fc receptor; IgG, immunoglobulin G.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Pregnancy is a situation of semi-allogenic immunological tolerance with regard to the fetus. The mechanisms of tolerance are described as uterine changes induced by the syncytiotrophoblast over: cytokines, T and natural killer (NK) lymphocytic subpopulations and complement, as well as the presence of human leukocyte antigen (HLA)-C class II, HLA-E and HLA-G. Moreover, systemic immunological changes are also produced: thymic involution through progesterone, decreased NK activity and a change toward an anti-inflammatory profile of cytokines (T helper cells [Th2]).<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Monoclonal antibodies (mAb) have revolutionized the treatment of autoimmune and inflammatory diseases, so frequent among women of childbearing age. Therefore, their utilization before or during pregnancy, is sometimes proposed, as a question of clinical practice. The mAb used, at the present time, are not apt for utilization during pregnancy<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> and there are no controlled studies in pregnant women. According to the Unites States Food and Drug Administration (FDA), these mAb are classified as category B (infliximab), as are their biosimilars, adalimumab, etanercept, golimumab and certolizumab pegol [CZP]), and as C (rituximab, tocilizumab and abatacept). There have been no significant differences in the rate of abortions among patients exposed to infliximab and <span class="elsevierStyleItalic">naïve</span> patients.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">To understand the process of placental transfer of mAb would help us to evaluate the risk of beginning or maintaining their administration during pregnancy. Nutrients are transferred to the fetus through a maternal layer of syncytiotrophoblasts and another of endothelium (fetal capillaries) by simple diffusion or using transport proteins. Toxins are returned by the fetus to the maternal circulation to be eliminated. Composed of low molecular weight (<500<span class="elsevierStyleHsp" style=""></span>Da), like O<span class="elsevierStyleInf">2</span> and amino acids, they diffuse passively through the placenta, but those with a high molecular weight require transport proteins to cross it. Immunoglobulin G (IgG) has a molecular weight of 160<span class="elsevierStyleHsp" style=""></span>kDa and crosses the placenta through the neonatal Fc receptor (FcRn) present in the syncytiotrophoblast cells.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The structure of most of the mAb utilized contains a constant region of IgG1 (Fc) and, during the first 20–22 weeks of pregnancy, there is a minimal active transfer because of the absence of FcRn. Transport across the placenta increases significantly toward the third trimester of the pregnancy (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Certolizumab pegol contains a PEGylated Fab fragment of the anti-tumor necrosis factor (TNF) antibody, and lacks the Fc fragment. Therefore, CZP crosses the placenta by passive diffusion more than by active transport utilizing FcRn, and, thus, the placental transfer of CZP must be minimal.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Likewise, although it cannot be explained by the FcRn system, observations on the levels of etanercept in umbilical cord have demonstrated that the rate of placental transfer is very low.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Mahadevan et al.,<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> showed that concentrations of infliximab and adalimumab, but not CZP, are greater in umbilical cord than in maternal serum; mean levels of infliximab and adalimumab in cord reach concentrations between 150% and 160% greater than the concentrations in maternal serum.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">There are other circumstances in which placental transfer of antibodies after weeks 20–22 can be detrimental to the fetus/neonate. Typically, in cases of rheumatoid arthritis and systemic lupus erythematosus, the passage of anti-Ro/SSA and/or anti-La/SSB autoantibodies of IgG isotype can cause an eruption due to exposure to the sun or the development of congenital heart block, which affects roughly 2% of fetuses/neonates of patients who have these autoantibodies.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">With the lack of data on the safety of mAb, the performance of clinical trials in pregnant patients is ruled out for ethical considerations, and the decision to use them would depend in each case on the clinical situation, as well as that of the potential benefits and risks for the mother, fetus or newborn. Long-term observational studies would enable us to confirm the efficacy and safety of category B mAb during pregnancy, to determine whether gestational exposure to mAb involves a long-term risk for the immune system being developed in the newborn, or should this vary depending on the trimester for exposure. It is important to consider that the administration of vaccines with alive or attenuated virus or bacteria, an indication that is present in certain vaccine calendars for newborns, for example, with bacillus Calmette-Guérin (BCG), with which, infection can have a fatal outcome.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> For these reasons, it is recommendable that they be postponed until the sixth month of life.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0035" class="elsevierStylePara elsevierViewall">LV: Abbvie, Roche Farma, Bristol-Myers Squibb, Pfizer, UCB, MSD and GSK; JGOB: nothing to declare; DHF: nothing to declare; FJLL: Abbvie, Roche Farma, Bristol-Myers Squibb, Pfizer, UCB and MSD.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of Interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Valor L, Ovalles-Bonilla JG, Hernández-Flórez D, López-Longo FJ. Una situación especial: tratamiento con anticuerpos monoclonales y embarazo en mujeres con enfermedades inflamatorias sistémicas. Reumatol Clin. 2016;12:359–360.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1440 "Ancho" => 2444 "Tamanyo" => 166803 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Immunoglobulin G crosses the placental barrier through the FcRn transport system, present in the syncytiotrophoblast cells. Fab, variable region; Fc, constant region of the immunoglobulin; FcRn, neonatal Fc receptor; IgG, immunoglobulin G.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rheumatoid arthritis and pregnancy: evolution of disease activity and pathophysiological considerations for drug use" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.M. Hazes" 1 => "P.G. Coulie" 2 => "V. Geenen" 3 => "S. Vermeire" 4 => "F. Carbonnel" 5 => "E. Louis" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rheumatology (Oxford)" "fecha" => "2011" "volumen" => "11" "paginaInicial" => "1955" "paginaFinal" => "1968" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0060" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "PART 71 – designation of Class A, Class B, Class C, Class D, and agency action" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A.M. Wylie" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Federal Register" "fecha" => "2008" "volumen" => "73" "paginaInicial" => "18" "paginaFinal" => "55" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0065" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pregnancy outcome in women who were exposed to anti-tumor necrosis factor agents: results from a national population register" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "K.L. Hyrich" 1 => "D.P. Symmons" 2 => "K.D. Watson" 3 => "A.J. Silman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.22028" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2006" "volumen" => "54" "paginaInicial" => "2701" "paginaFinal" => "2702" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16871549" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0070" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outcome of pregnancy in women receiving infliximab for the treatment of Crohn's disease and rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J.A. Katz" 1 => "C. Antoni" 2 => "G.F. Keenan" 3 => "D.E. Smith" 4 => "S.J. Jacobs" 5 => "G.R. Lichtenstein" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1572-0241.2004.30186.x" "Revista" => array:6 [ "tituloSerie" => "Am J Gastroenterol" "fecha" => "2004" "volumen" => "99" "paginaInicial" => "2385" "paginaFinal" => "2392" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15571587" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0075" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Placental transport of immunoglobulin G" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "N.E. Simister" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Vaccine" "fecha" => "2003" "volumen" => "21" "paginaInicial" => "3365" "paginaFinal" => "3369" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12850341" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1590865810605105" "estado" => "S300" "issn" => "15908658" ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0080" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "IgG placental transfer in healthy and pathological pregnancies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P. Palmeira" 1 => "C. Quinello" 2 => "A.L. Silveira-Lessa" 3 => "C.A. Zago" 4 => "M. Carneiro-Sampaio" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1155/2012/985646. Epub 2011 Oct 1" "Revista" => array:3 [ "tituloSerie" => "Clin Dev Immunol" "fecha" => "2012" "volumen" => "2012" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0085" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transplacental transfer of immunosuppressants and biologics used for the treatment of inflammatory bowel disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. Chaparro" 1 => "J.P. Gisbert" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Curr Pharm Biotechnol" "fecha" => "2011" "volumen" => "12" "paginaInicial" => "765" "paginaFinal" => "773" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0090" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Etanercept concentrations in maternal serum, umbilical cord serum, breast milk and child serum during breastfeeding" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "B.G. Berthelsen" 1 => "H. Fjeldsoe-Nielsen" 2 => "C.T. Nielsen" 3 => "E. Hellmuth" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rheumatology (Oxford)" "fecha" => "2010" "volumen" => "49" "paginaInicial" => "2225" "paginaFinal" => "2227" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0095" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "U. Mahadevan" 1 => "D.C. Wolf" 2 => "M. Dubinsky" 3 => "A. Cortot" 4 => "S.D. Lee" 5 => "C.A. Siegel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cgh.2012.11.011" "Revista" => array:6 [ "tituloSerie" => "Clin Gastroenterol Hepatol" "fecha" => "2013" "volumen" => "11" "paginaInicial" => "286" "paginaFinal" => "324" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23200982" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0100" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Case report: fatal case of disseminated BCG infection in an infant born to a mother taking infliximab for Crohn's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "K. Cheent" 1 => "J. Nolan" 2 => "S. Shariq" 3 => "L. Kiho" 4 => "A. Pal" 5 => "J. Arnold" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.crohns.2010.05.001" "Revista" => array:6 [ "tituloSerie" => "J Crohns Colitis" "fecha" => "2010" "volumen" => "4" "paginaInicial" => "603" "paginaFinal" => "605" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21122568" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735743/0000001200000006/v1_201611050033/S2173574316300910/v1_201611050033/en/main.assets" "Apartado" => array:4 [ "identificador" => "8400" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735743/0000001200000006/v1_201611050033/S2173574316300910/v1_201611050033/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574316300910?idApp=UINPBA00004M" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 14 | 14 | 28 |
| 2024 October | 84 | 34 | 118 |
| 2024 September | 105 | 23 | 128 |
| 2024 August | 102 | 32 | 134 |
| 2024 July | 107 | 36 | 143 |
| 2024 June | 99 | 38 | 137 |
| 2024 May | 114 | 40 | 154 |
| 2024 April | 125 | 26 | 151 |
| 2024 March | 129 | 35 | 164 |
| 2024 February | 88 | 35 | 123 |
| 2024 January | 105 | 29 | 134 |
| 2023 December | 110 | 26 | 136 |
| 2023 November | 103 | 37 | 140 |
| 2023 October | 111 | 38 | 149 |
| 2023 September | 127 | 37 | 164 |
| 2023 August | 153 | 15 | 168 |
| 2023 July | 99 | 21 | 120 |
| 2023 June | 119 | 24 | 143 |
| 2023 May | 106 | 28 | 134 |
| 2023 April | 89 | 7 | 96 |
| 2023 March | 180 | 51 | 231 |
| 2023 February | 142 | 41 | 183 |
| 2023 January | 113 | 22 | 135 |
| 2022 December | 142 | 35 | 177 |
| 2022 November | 138 | 28 | 166 |
| 2022 October | 113 | 42 | 155 |
| 2022 September | 105 | 34 | 139 |
| 2022 August | 92 | 50 | 142 |
| 2022 July | 131 | 43 | 174 |
| 2022 June | 113 | 40 | 153 |
| 2022 May | 164 | 32 | 196 |
| 2022 April | 120 | 54 | 174 |
| 2022 March | 129 | 46 | 175 |
| 2022 February | 166 | 27 | 193 |
| 2022 January | 332 | 32 | 364 |
| 2021 December | 635 | 47 | 682 |
| 2021 November | 523 | 62 | 585 |
| 2021 October | 488 | 80 | 568 |
| 2021 September | 941 | 56 | 997 |
| 2021 August | 1073 | 62 | 1135 |
| 2021 July | 306 | 41 | 347 |
| 2021 June | 212 | 49 | 261 |
| 2021 May | 217 | 45 | 262 |
| 2021 April | 347 | 89 | 436 |
| 2021 March | 209 | 27 | 236 |
| 2021 February | 156 | 26 | 182 |
| 2021 January | 135 | 24 | 159 |
| 2020 December | 107 | 29 | 136 |
| 2020 November | 104 | 19 | 123 |
| 2020 October | 93 | 12 | 105 |
| 2020 September | 142 | 31 | 173 |
| 2020 August | 102 | 12 | 114 |
| 2020 July | 84 | 22 | 106 |
| 2020 June | 87 | 33 | 120 |
| 2020 May | 87 | 19 | 106 |
| 2020 April | 76 | 27 | 103 |
| 2020 March | 20 | 6 | 26 |
| 2020 February | 1 | 0 | 1 |
| 2018 December | 2 | 0 | 2 |
| 2018 May | 8 | 2 | 10 |
| 2018 April | 78 | 3 | 81 |
| 2018 March | 101 | 6 | 107 |
| 2018 February | 60 | 4 | 64 |
| 2018 January | 34 | 4 | 38 |
| 2017 December | 59 | 11 | 70 |
| 2017 November | 61 | 6 | 67 |
| 2017 October | 35 | 2 | 37 |
| 2017 September | 43 | 9 | 52 |
| 2017 August | 40 | 8 | 48 |
| 2017 July | 49 | 12 | 61 |
| 2017 June | 53 | 21 | 74 |
| 2017 May | 55 | 19 | 74 |
| 2017 April | 57 | 11 | 68 |
| 2017 March | 46 | 20 | 66 |
| 2017 February | 25 | 6 | 31 |
| 2017 January | 52 | 26 | 78 |
| 2016 December | 59 | 37 | 96 |
| 2016 November | 53 | 36 | 89 |
| 2016 October | 4 | 7 | 11 |
Show all
