Long-Term Safety of In Utero Exposure to Anti-TNF alpha 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, IA, Lopez-Serrano, P, Casanova, MJ, Gompertz, M, Vitor, S, Arroyo, M, Pugliese, D, Zabana, Y, Vicente, R, Aguas, M, Shitrit, ABG, Gutierrez, A, Doherty, GA, Fernandez-Salazar, L, Cadilla, JM, Huguet, JM, O'Toole, A, Stasi, E, Marcos, NM, Villoria, A, Karmiris, K, Rahier, JF, Rodriguez, C, Palomares, MDL, Fiorino, G, Benitez, JM, Principi, M, Naftali, T, Taxonera, C, Mantzaris, G, Sebkova, L, Iade, B, Lissner, D, Bradley, IF, Roman, ALS, 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, FJM and Gisbert, JP
Publicada:
1 mar 2018
Resumen:
OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNF alpha) 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-TNF alpha 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-TNF alpha 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-TNF alpha 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-TNF alpha 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-TNF alpha drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.
Filiaciones:
Chaparro, M:
Hosp Univ La Princesa, Gastroenterol Units, Inst Invest Sanitaria Princesa IIS IP, Madrid, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Verreth, A:
Katholieke Univ Leuven, Univ Hosp Leuven, Dept Gastroenterol, Leuven, Belgium
Katholieke Univ Leuven, Univ Hosp Leuven, Dept Pediat Gastroenterol, Leuven, Belgium
Lobaton, T:
Hosp Badalona Germans Trias & Pujol, Badalona, Spain
CIBEREHD, Badalona, Spain
Gravito-Soares, E:
Ctr Hosp & Univ Coimbra, Coimbra, Portugal
Julsgaard, M:
Aarhus Univ Hosp, Dept Gastroenterol & Hepatol, Aarhus, Denmark
Savarino, E:
Univ Padua, Padua, Italy
Magro, F:
Ctr Hosp Sao Joao, Porto, Portugal
Biron, IA:
Rabin Med Ctr, Gastroenterol Devis, Petah Tiqwa, Israel
Lopez-Serrano, P:
Hosp Univ Fdn Alcorcon, Alcorcon, Spain
Casanova, MJ:
Hosp Univ La Princesa, Gastroenterol Units, Inst Invest Sanitaria Princesa IIS IP, Madrid, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Gompertz, M:
Hosp Clin Barcelona, Barcelona, Spain
CIBERehd, Barcelona, Spain
Vitor, S:
Ctr Hosp Lisboa Norte, Hosp Santa Maria, Lisbon, Portugal
Arroyo, M:
Hosp Clin Univ Lozano Blesa, IIS Aragon, CIBEREHD, Zaragoza, Spain
Pugliese, D:
Fdn Policlin Gemelli Univ Cattolica, IBD Unit, Presidio Columbus, Rome, Italy
Zabana, Y:
Hosp Univ Mutua Terrassa, Terrassa, Spain
CIBEREHD, Terrassa, Spain
Vicente, R:
Hosp Univ Miguel Servet, Zaragoza, Spain
Aguas, M:
Hosp Univ La Fe, Valencia, Spain
CIBEREHD, Valencia, Spain
Shitrit, ABG:
Shaare Zedek Med Ctr, Jerusalem, Israel
Gutierrez, A:
Hosp Gen Univ Alicante, Alicante, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Alicante, Spain
Doherty, GA:
St Vincents Univ Hosp, Dublin, Ireland
Fernandez-Salazar, L:
Hosp Clin Univ Valladolid, Valladolid, Spain
Cadilla, JM:
Hosp Univ Alvaro Cunqueiro, Vigo, Spain
Huguet, JM:
Hosp Gen Univ Valencia, Valencia, Spain
O'Toole, A:
Beaumont Hosp, Dublin, Ireland
Stasi, E:
IRCCS Saverio de Bellis, Castellana Grotte, Italy
Marcos, NM:
Hosp Univ Infanta Sofi, Madrid, Spain
Villoria, A:
Univ Autonoma Barcelona, Hosp Univ Parc Tauli, Inst Invest & Innovacio Parc Tauli, Dept Med,CIBERehd,Inst Salud Carlos III, Sabadell, Spain
Karmiris, K:
Venizeleio Gen Hosp, Iraklion, Greece
Rahier, JF:
CHU UCL Namur, Yvoir, Belgium
Rodriguez, C:
Complejo Univ Navarra, Pamplona, Spain
Palomares, MDL:
Hosp Univ A Coruna, Coruna, Spain
Fiorino, G:
Humanitas Clin & Res Inst, IBD Ctr, Milan, Italy
Humanitas Univ, Dept Biomed Sci, Milan, Italy
Benitez, JM:
Hosp Univ Reina Sofia, Cordoba, Spain
IMIBIC, Cordoba, Spain
Principi, M:
Azienda Policlin Osped Univ Bari, Bari, Italy
Naftali, T:
Tel Aviv Univ, Meir Hosp Kfar Saba, Tel Aviv, Israel
Taxonera, C:
Hosp Clin San Carlos, Madrid, Spain
IdISSC, Madrid, Spain
Mantzaris, G:
Evangelismos Med Ctr, Athens, Greece
Ophthalmiatre Athinon Hosp, Athens, Greece
Polyclin Hosp, Athens, Greece
Sebkova, L:
Azienda Osped Pugliese Ciaccio, Catanzaro, Italy
Iade, B:
Hosp Clin Montevideo, Montevideo, Uruguay
Lissner, D:
Univ Med Berlin, Campus Benjamin Franklin, Berlin, Germany
Bradley, IF:
Hosp Manises, Manises, Spain
Roman, ALS:
Hosp Ramon & Cajal, Madrid, Spain
Marin-Jimenez, I:
Hosp Gen Univ Gregorio Maranon, Madrid, Spain
IiSGM, Madrid, Spain
Merino, O:
Hosp Univ Cruces, Baracaldo, Spain
Sierra, M:
Complejo Univ Leon, Leon, Spain
Van Domselaar, M:
Hosp Torrejon, Torrejon De Ardoz, Spain
Caprioli, F:
Univ Milan, Gastroenterol & Endoscopy Unit, Fdn IRCCS Ca Granda, Osped Policlin Milano, Milan, Italy
Univ Milan, Dept Pathophysiol & Transplantat, Milan, Italy
Guerra, I:
Hosp Univ Fuenlabrada, Fuenlabrada, Spain
Peixe, P:
Ctr Hosp Lisboa Ocidental, Lisbon, Portugal
Piqueras, M:
Consorci Sanitari Terrasa, Terrassa, Spain
Rodriguez-Lago, I:
Hosp Galdakao, Vizcaya, Spain
Ber, Y:
Hosp San Jorge, Huesca, Spain
van Hoeve, K:
Katholieke Univ Leuven, Dept Paediat, Univ Hosp Leuven, Leuven, Belgium
:
Hosp Badalona Germans Trias & Pujol, Badalona, Spain
CIBEREHD, Badalona, Spain
Gravito-Soares, M:
Ctr Hosp & Univ Coimbra, Coimbra, Portugal
Rudbeck-Resdal, D:
Aarhus Univ Hosp, Dept Gastroenterol & Hepatol, Aarhus, Denmark
Bartolo, O:
Univ Padua, Padua, Italy
Peixoto, A:
Ctr Hosp Sao Joao, Porto, Portugal
Martin, G:
Rabin Med Ctr, Gastroenterol Devis, Petah Tiqwa, Israel
Armuzzi, A:
Fdn Policlin Gemelli Univ Cattolica, IBD Unit, Presidio Columbus, Rome, Italy
Garre, A:
Hosp Univ La Princesa, Gastroenterol Units, Inst Invest Sanitaria Princesa IIS IP, Madrid, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Donday, MG:
Hosp Univ La Princesa, Gastroenterol Units, Inst Invest Sanitaria Princesa IIS IP, Madrid, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
de Carpi, FJM:
Hosp St Joan de Deu, Barcelona, Spain
Gisbert, JP:
Hosp Univ La Princesa, Gastroenterol Units, Inst Invest Sanitaria Princesa IIS IP, Madrid, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
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