Long-Term Safety of In Utero Exposure to Anti-TNFa Drugs for the Treatment of Inflammatory Bowel Disease: Results from the Multicenter European TEDDY Study.
Por:
Chaparro M, Verreth A, Lobaton T, Gravito-Soares E, Julsgaard M, Savarino E, Magro F, Biron AI, Lopez-Serrano P, Casanova MJ, Gompertz M, Vitor S, Arroyo M, Pugliese D, Zabana Y, Vicente R, Aguas M, Shitrit BA, Gutierrez A, Doherty GA, Fernandez-Salazar L, Cadilla MJ, Huguet JM, O'Toole A, Stasi E, Marcos MN, Villoria A, Karmiris K, Rahier JF, Rodriguez C, Palomares DM, Fiorino G, Benitez JM, Principi M, Naftali T, Taxonera C, Mantzaris G, Sebkova L, Iade B, Lissner D, Bradley FI, Roman LA, Marin-Jimenez I, Merino O, Sierra M, Van Domselaar M, Caprioli F, Guerra I, Peixe P, Piqueras M, Rodriguez-Lago I, Ber Y, van Hoeve K, Torres P, Gravito-Soares M, Rudbeck-Resdal D, Bartolo O, Peixoto A, Martin G, Armuzzi A, Garre A, Donday MG, de Carpi MFJ and Gisbert JP
Publicada:
1 mar 2018
Ahead of Print:
20 feb 2018
Resumen:
OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFa) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFa drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFa medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFa agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. RESULTS: The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNFa agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5-4.3)). CONCLUSIONS: In utero exposure to anti-TNFa drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.
Filiaciones:
Chaparro M:
Gastroenterology Units Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
Verreth A:
Department of Gastroenterology and Department of Pediatric Gastroenterology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
Lobaton T:
Hospital Universitari Germans Trias i Pujol and CIBEREHD, Badalona, Spain
Gravito-Soares E:
Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
Julsgaard M:
Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
Savarino E:
University of Padua, Padua, Italy
Magro F:
Centro Hospitalar São João, Porto, Portugal
Biron AI:
Gastroenterology Devision, Rabin Medical Center, Petach Tikva, Israel
Lopez-Serrano P:
Hospital Universitario Fundación Alcorcón, Alcorcón, Spain
Casanova MJ:
Gastroenterology Units Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
Gompertz M:
Hospital Clinic and CIBEREHD, Barcelona, Spain
Vitor S:
Hospital de Santa Maria - Centro Hospitalar Lisboa Norte, Lisboa, Portugal
Arroyo M:
Hospital Clinico Universitario Lozano Blesa, IIS Aragon, CIBEREHD, Zaragoza, Spain
Pugliese D:
IBD Unit, Presidio Columbus, Fondazione Policlinico Gemelli Università Cattolica, Roma, Italy
Zabana Y:
Hospital Universitari Mutua de Terrassa and CIBEREHD, Terrassa, Spain
Vicente R:
Hospital Universitario Miguel Servet, Zaragoza, Spain
Aguas M:
Hospital Universitario La Fe and CIBEREHD, Valencia, Spain
Shitrit BA:
Shaare Zedek Medical Center, Jerusalem, Israel
:
Hospital General Universitario de Alicante and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Alicante, Spain
Doherty GA:
St. Vincents University Hospital, Dublin, Ireland
Fernandez-Salazar L:
Hospital Clínico Universitario de Valladolid, Valladolid, Spain
Cadilla MJ:
Hospital Universitario Alvaro Cunqueiro, Vigo, Spain
Huguet JM:
Hospital General Universitario de Valencia, Valencia, Spain
O'Toole A:
Beaumont Hospital, Dublin, Ireland
Stasi E:
IRCCS Saverio de Bellis, Castellana Grotte, Italy
Marcos MN:
Hospital Universitario Infanta Sofia, Madrid, Spain
Villoria A:
Hospital Universitari Parc Taulí.Institut d'Investigació i Innovació Parc Taulí. Departament de Medicina, Universitat Autònoma de Barcelona.CIBERehd, Instituto de Salud Carlos III, Sabadell, Spain
Karmiris K:
Venizeleio General Hospital, Heraklion, Greece
Rahier JF:
CHU UCL Namur, Yvoir, Belgium
Rodriguez C:
Complejo Universitario de Navarra, Pamplona, Spain
Palomares DM:
Hospital Universitario A Coruña, Coruña, Spain
Fiorino G:
IBD Center, Humanitas Clinical and Research Institute, Rozzano, Milan, Italy and Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy
Benitez JM:
Hospital Universitario Reina Sofia and IMIBIC, Córdoba, Spain
Principi M:
Azienda Policlinico Ospedaliero-Universitaria di Bari, Bari, Italy
Naftali T:
Meir Hospital Kfar saba Tel Aviv University, Tel Aviv, Israel
Taxonera C:
Hospital Clínico San Carlos and IdISSC, Madrid, Spain
Mantzaris G:
Evangelismos, Ophthalmiatreion Athinon and Polyclinic Hospitals, Athens, Greece
Sebkova L:
Azienda Ospedaliera "Pugliese-Ciaccio", Catanzaro, Italy
Iade B:
Hospital de Clinicas, Montevideo, Uruguay
Lissner D:
Universitatsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
Bradley FI:
Hospital de Manises, Manises, Spain
Roman LA:
Hospital Ramón y Cajal, Madrid, Spain
Marin-Jimenez I:
Hospital General Universitario Gregorio Marañón and IiSGM, Madrid, Spain
Merino O:
Hospital Universitario de Cruces, Baracaldo, Spain
Sierra M:
Complejo Universitario de León, León, Spain
Van Domselaar M:
Hospital de Torrejón, Torrejón de Ardoz, Spain
Caprioli F:
Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano AND Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
Guerra I:
Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain
Peixe P:
Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal
Piqueras M:
Consorci Sanitari de Terrasa, Terrasa, Spain
Rodriguez-Lago I:
Hospital de Galdakao, Vizcaya, Spain
Ber Y:
Hospital San Jorge, Huesca, Spain
van Hoeve K:
Department of Paediatrics, University Hospitals Leuven, KU Leuven, Leuven, Belgium
Torres P:
Hospital Universitari Germans Trias i Pujol and CIBEREHD, Badalona, Spain
Gravito-Soares M:
Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
Rudbeck-Resdal D:
Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
Bartolo O:
University of Padua, Padua, Italy
Peixoto A:
Centro Hospitalar São João, Porto, Portugal
Martin G:
Gastroenterology Devision, Rabin Medical Center, Petach Tikva, Israel
Armuzzi A:
IBD Unit, Presidio Columbus, Fondazione Policlinico Gemelli Università Cattolica, Roma, Italy
Garre A:
Gastroenterology Units Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
Donday MG:
Gastroenterology Units Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
de Carpi MFJ:
Hospital Sant Joan de Déu, Barcelona, Spain
Gisbert JP:
Gastroenterology Units Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
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