Long-term safety of in utero exposure to anti-TNFα drugs for the treatment of inflammatory bowel disease: Results from the multicenter European TEDDY study

M. Chaparro, A. Verreth, T. Lobaton, E. Gravito-Soares, M. Julsgaard, E. Savarino, F. Magro, I.A. Biron, P. Lopez-Serrano, M.J. Casanova, M. Gompertz, S. Vitor, M. Arroyo, D. Pugliese, Y. Zabana, R. Vicente, M. Aguas, A.B.-G. Shitrit, A. Gutierrez, G.A. Doherty & 44 others L. Fernandez-Salazar, J.M. Cadilla, J.M. Huguet, A. O’Toole, E. Stasi, N.M. Marcos, A. Villoria, K. Karmiris, J.F. Rahier, C. Rodriguez, M. Diz-Lois Palomares, G. Fiorino, J.M. Benitez, M. Principi, T. Naftali, C. Taxonera, G. Mantzaris, L. Sebkova, B. Iade, D. Lissner, I.F. Bradley, A.L.-S. Roman, I. Marin-Jimenez, O. Merino, M. Sierra, M. Van Domselaar, F. Caprioli, I. Guerra, P. Peixe, M. Piqueras, I. Rodriguez-Lago, Y. Ber, K. van Hoeve, P. Torres, M. Gravito-Soares, D. Rudbeck-Resdal, O. Bartolo, A. Peixoto, G. Martin, A. Armuzzi, A. Garre, M.G. Donday, F.J. Martín de Carpi, J.P. Gisbert

Research output: Contribution to journalArticle

Abstract

OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with infl ammatory bowel disease (IBD) who were exposed to anti-TNFα 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-TNFα 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-TNFα 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-TNFα 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-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children. © 2018 by the American College of Gastroenterology.
Original languageEnglish
Pages (from-to)396-403
Number of pages8
JournalAmerican Journal of Gastroenterology
Volume113
Issue number3
DOIs
Publication statusPublished - 2018

Fingerprint

Inflammatory Bowel Diseases
Tumor Necrosis Factor-alpha
Safety
Pharmaceutical Preparations
Infection
Mothers
Pregnancy
Therapeutics
Multivariate Analysis
Incidence
Multicenter Studies
Cohort Studies
Regression Analysis
Parturition
Confidence Intervals
Population

Keywords

  • mercaptopurine
  • tumor necrosis factor inhibitor, adult
  • appendicitis
  • Article
  • child
  • childbirth
  • cohort analysis
  • conception
  • controlled study
  • Coxsackie virus infection
  • disease severity
  • drug safety
  • Europe
  • female
  • follow up
  • gastrointestinal infection
  • human
  • incidence
  • infection risk
  • infectious arthritis
  • inflammatory bowel disease
  • male
  • mastoiditis
  • meningitis
  • mononucleosis
  • multicenter study
  • outcome assessment
  • pertussis
  • prenatal drug exposure
  • priority journal
  • respiratory tract infection
  • retrospective study
  • sialoadenitis
  • sinusitis
  • skin infection
  • stomatitis
  • time to treatment
  • tonsillitis
  • urinary tract infection

Cite this

Long-term safety of in utero exposure to anti-TNFα drugs for the treatment of inflammatory bowel disease: Results from the multicenter European TEDDY study. / Chaparro, M.; Verreth, A.; Lobaton, T.; Gravito-Soares, E.; Julsgaard, M.; Savarino, E.; Magro, F.; Biron, I.A.; Lopez-Serrano, P.; Casanova, M.J.; Gompertz, M.; Vitor, S.; Arroyo, M.; Pugliese, D.; Zabana, Y.; Vicente, R.; Aguas, M.; Shitrit, A.B.-G.; Gutierrez, A.; Doherty, G.A.; Fernandez-Salazar, L.; Cadilla, J.M.; Huguet, J.M.; O’Toole, A.; Stasi, E.; Marcos, N.M.; Villoria, A.; Karmiris, K.; Rahier, J.F.; Rodriguez, C.; Diz-Lois Palomares, M.; Fiorino, G.; Benitez, J.M.; Principi, M.; Naftali, T.; Taxonera, C.; Mantzaris, G.; Sebkova, L.; Iade, B.; Lissner, D.; Bradley, I.F.; Roman, A.L.-S.; 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, M.G.; Martín de Carpi, F.J.; Gisbert, J.P.

In: American Journal of Gastroenterology, Vol. 113, No. 3, 2018, p. 396-403.

Research output: Contribution to journalArticle

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, AB-G, 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, Diz-Lois Palomares, M, Fiorino, G, Benitez, JM, Principi, M, Naftali, T, Taxonera, C, Mantzaris, G, Sebkova, L, Iade, B, Lissner, D, Bradley, IF, Roman, AL-S, 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, Martín de Carpi, FJ & Gisbert, JP 2018, 'Long-term safety of in utero exposure to anti-TNFα drugs for the treatment of inflammatory bowel disease: Results from the multicenter European TEDDY study', American Journal of Gastroenterology, vol. 113, no. 3, pp. 396-403. https://doi.org/10.1038/ajg.2017.501
Chaparro, M. ; Verreth, A. ; Lobaton, T. ; Gravito-Soares, E. ; Julsgaard, M. ; Savarino, E. ; Magro, F. ; Biron, I.A. ; Lopez-Serrano, P. ; Casanova, M.J. ; Gompertz, M. ; Vitor, S. ; Arroyo, M. ; Pugliese, D. ; Zabana, Y. ; Vicente, R. ; Aguas, M. ; Shitrit, A.B.-G. ; Gutierrez, A. ; Doherty, G.A. ; Fernandez-Salazar, L. ; Cadilla, J.M. ; Huguet, J.M. ; O’Toole, A. ; Stasi, E. ; Marcos, N.M. ; Villoria, A. ; Karmiris, K. ; Rahier, J.F. ; Rodriguez, C. ; Diz-Lois Palomares, M. ; Fiorino, G. ; Benitez, J.M. ; Principi, M. ; Naftali, T. ; Taxonera, C. ; Mantzaris, G. ; Sebkova, L. ; Iade, B. ; Lissner, D. ; Bradley, I.F. ; Roman, A.L.-S. ; 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, M.G. ; Martín de Carpi, F.J. ; Gisbert, J.P. / Long-term safety of in utero exposure to anti-TNFα drugs for the treatment of inflammatory bowel disease: Results from the multicenter European TEDDY study. In: American Journal of Gastroenterology. 2018 ; Vol. 113, No. 3. pp. 396-403.
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title = "Long-term safety of in utero exposure to anti-TNFα drugs for the treatment of inflammatory bowel disease: Results from the multicenter European TEDDY study",
abstract = "OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with infl ammatory bowel disease (IBD) who were exposed to anti-TNFα 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-TNFα 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-TNFα 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-TNFα 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-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children. {\circledC} 2018 by the American College of Gastroenterology.",
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author = "M. Chaparro and A. Verreth and T. Lobaton and E. Gravito-Soares and M. Julsgaard and E. Savarino and F. Magro and I.A. Biron and P. Lopez-Serrano and M.J. Casanova and M. Gompertz and S. Vitor and M. Arroyo and D. Pugliese and Y. Zabana and R. Vicente and M. Aguas and A.B.-G. Shitrit and A. Gutierrez and G.A. Doherty and L. Fernandez-Salazar and J.M. Cadilla and J.M. Huguet and A. O’Toole and E. Stasi and N.M. Marcos and A. Villoria and K. Karmiris and J.F. Rahier and C. Rodriguez and {Diz-Lois Palomares}, M. and G. Fiorino and J.M. Benitez and M. Principi and T. Naftali and C. Taxonera and G. Mantzaris and L. Sebkova and B. Iade and D. Lissner and I.F. Bradley and A.L.-S. Roman and I. Marin-Jimenez and O. Merino and M. Sierra and {Van Domselaar}, M. and F. Caprioli and I. Guerra and P. Peixe and M. Piqueras and I. Rodriguez-Lago and Y. Ber and {van Hoeve}, K. and P. Torres and M. Gravito-Soares and D. Rudbeck-Resdal and O. Bartolo and A. Peixoto and G. Martin and A. Armuzzi and A. Garre and M.G. Donday and {Mart{\'i}n de Carpi}, F.J. and J.P. Gisbert",
note = "cited By 6",
year = "2018",
doi = "10.1038/ajg.2017.501",
language = "English",
volume = "113",
pages = "396--403",
journal = "American Journal of Gastroenterology",
issn = "0002-9270",
publisher = "Nature Publishing Group",
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TY - JOUR

T1 - Long-term safety of in utero exposure to anti-TNFα drugs for the treatment of inflammatory bowel disease: Results from the multicenter European TEDDY study

AU - Chaparro, M.

AU - Verreth, A.

AU - Lobaton, T.

AU - Gravito-Soares, E.

AU - Julsgaard, M.

AU - Savarino, E.

AU - Magro, F.

AU - Biron, I.A.

AU - Lopez-Serrano, P.

AU - Casanova, M.J.

AU - Gompertz, M.

AU - Vitor, S.

AU - Arroyo, M.

AU - Pugliese, D.

AU - Zabana, Y.

AU - Vicente, R.

AU - Aguas, M.

AU - Shitrit, A.B.-G.

AU - Gutierrez, A.

AU - Doherty, G.A.

AU - Fernandez-Salazar, L.

AU - Cadilla, J.M.

AU - Huguet, J.M.

AU - O’Toole, A.

AU - Stasi, E.

AU - Marcos, N.M.

AU - Villoria, A.

AU - Karmiris, K.

AU - Rahier, J.F.

AU - Rodriguez, C.

AU - Diz-Lois Palomares, M.

AU - Fiorino, G.

AU - Benitez, J.M.

AU - Principi, M.

AU - Naftali, T.

AU - Taxonera, C.

AU - Mantzaris, G.

AU - Sebkova, L.

AU - Iade, B.

AU - Lissner, D.

AU - Bradley, I.F.

AU - Roman, A.L.-S.

AU - Marin-Jimenez, I.

AU - Merino, O.

AU - Sierra, M.

AU - Van Domselaar, M.

AU - Caprioli, F.

AU - Guerra, I.

AU - Peixe, P.

AU - Piqueras, M.

AU - Rodriguez-Lago, I.

AU - Ber, Y.

AU - van Hoeve, K.

AU - Torres, P.

AU - Gravito-Soares, M.

AU - Rudbeck-Resdal, D.

AU - Bartolo, O.

AU - Peixoto, A.

AU - Martin, G.

AU - Armuzzi, A.

AU - Garre, A.

AU - Donday, M.G.

AU - Martín de Carpi, F.J.

AU - Gisbert, J.P.

N1 - cited By 6

PY - 2018

Y1 - 2018

N2 - OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with infl ammatory bowel disease (IBD) who were exposed to anti-TNFα 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-TNFα 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-TNFα 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-TNFα 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-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children. © 2018 by the American College of Gastroenterology.

AB - OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with infl ammatory bowel disease (IBD) who were exposed to anti-TNFα 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-TNFα 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-TNFα 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-TNFα 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-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children. © 2018 by the American College of Gastroenterology.

KW - mercaptopurine

KW - tumor necrosis factor inhibitor, adult

KW - appendicitis

KW - Article

KW - child

KW - childbirth

KW - cohort analysis

KW - conception

KW - controlled study

KW - Coxsackie virus infection

KW - disease severity

KW - drug safety

KW - Europe

KW - female

KW - follow up

KW - gastrointestinal infection

KW - human

KW - incidence

KW - infection risk

KW - infectious arthritis

KW - inflammatory bowel disease

KW - male

KW - mastoiditis

KW - meningitis

KW - mononucleosis

KW - multicenter study

KW - outcome assessment

KW - pertussis

KW - prenatal drug exposure

KW - priority journal

KW - respiratory tract infection

KW - retrospective study

KW - sialoadenitis

KW - sinusitis

KW - skin infection

KW - stomatitis

KW - time to treatment

KW - tonsillitis

KW - urinary tract infection

U2 - 10.1038/ajg.2017.501

DO - 10.1038/ajg.2017.501

M3 - Article

VL - 113

SP - 396

EP - 403

JO - American Journal of Gastroenterology

JF - American Journal of Gastroenterology

SN - 0002-9270

IS - 3

ER -