Original Research
27 September 2022

Benefits and Risks Associated With Continuation of Anti–Tumor Necrosis Factor After 24 Weeks of Pregnancy in Women With Inflammatory Bowel Disease: A Nationwide Emulation Trial

Publication: Annals of Internal Medicine
Volume 175, Number 10
Visual Abstract. Anti-TNF After 24 Weeks of Pregnancy.
Anti–tumor necrosis factor (anti-TNF) is an effective treatment for inflammatory bowel disease (IBD). This retrospective cohort study compared continuing versus stopping anti-TNF treatment after 24 weeks of pregnancy with respect to maternal and fetal outcomes in pregnant women with IBD.

Abstract

Background:

Continuation of biologics for inflammatory disorders during pregnancy is still a difficult decision. Many women with inflammatory bowel diseases (IBDs) stop anti–tumor necrosis factor (anti-TNF) treatment after 24 weeks.

Objective:

To evaluate the benefits and risks of anti-TNF continuation after 24 weeks of pregnancy for mothers with IBD and their offspring.

Design:

Target trial emulation between 2010 and 2020.

Setting:

Nationwide population-based study using the Système National des Données de Santé.

Patients:

All pregnancies with birth exposed to anti-TNF between conception and 24 weeks of pregnancy in women with IBD.

Intervention:

Continuation of anti-TNF after 24 weeks of pregnancy.

Measurements:

Occurrence of maternal IBD relapse up to 6 months after pregnancy, adverse pregnancy outcomes, and serious infections in the offspring during the first 5 years of life was compared according to anti-TNF continuation after 24 weeks of pregnancy using inverse probability–weighted marginal models.

Results:

A total of 5293 pregnancies were included; among them, anti-TNF treatment was discontinued before 24 weeks for 2890 and continued beyond 24 weeks for 2403. Continuation of anti-TNF was associated with decreased frequencies of maternal IBD relapse (35.8% vs. 39.0%; adjusted risk ratio [aRR], 0.93 [95% CI, 0.86 to 0.99]) and prematurity (7.6% vs. 8.9%; aRR, 0.82 [CI, 0.68 to 0.99]). No difference according to anti-TNF continuation was found regarding stillbirths (0.4% vs. 0.2%; aRR, 2.16 [CI, 0.64 to 7.81]), small weight for gestational age births (13.1% vs. 12.9%; aRR, 1.01 [CI, 0.88 to 1.17]), and serious infections in the offspring (54.2 vs. 50.2 per 1000 person-years; adjusted hazard ratio, 1.08 [CI, 0.94 to 1.25]).

Limitation:

Algorithms rather than clinical data were used to identify patients with IBD, pregnancies, and serious infections.

Conclusion:

Continuation of anti-TNF after 24 weeks of pregnancy appears beneficial regarding IBD activity and prematurity, while not affecting neonatal outcomes and serious infections in the offspring.

Primary Funding Source:

None.

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Supplemental Material

Supplement. Supplementary Material

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Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 175Number 10October 2022
Pages: 1374 - 1382

History

Published online: 27 September 2022
Published in issue: October 2022

Keywords

Authors

Affiliations

EPI-PHARE, Épidémiologie des produits de santé, Saint-Denis, and Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre & Université Paris-Saclay, Le Kremlin Bicêtre, France (A.M.)
EPI-PHARE, Épidémiologie des produits de santé, Saint-Denis, France (A.N., J.D., A.W., R.D.)
EPI-PHARE, Épidémiologie des produits de santé, Saint-Denis, France (A.N., J.D., A.W., R.D.)
EPI-PHARE, Épidémiologie des produits de santé, Saint-Denis, France (A.N., J.D., A.W., R.D.)
Franck Carbonnel, MD, PhD https://orcid.org/0000-0002-4779-5168
Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre & Université Paris-Saclay, Le Kremlin Bicêtre, France (F.C.).
Rosemary Dray-Spira, MD, PhD https://orcid.org/0000-0001-7646-3667
EPI-PHARE, Épidémiologie des produits de santé, Saint-Denis, France (A.N., J.D., A.W., R.D.)
Reproducible Research Statement: Study protocol and statistical code: Not available. Data set: The authors had access to the SNDS database in application of the provisions of articles R. 1461-12 et seq. of the French Public Health Code and the French Data Protection Authority decision CNIL-2016-316. Future researchers can request access via the health data hub at https://documentation-snds.health-data-hub.fr/introduction/03-acces-snds.html#les-acces-sur-projet.
Corresponding Author: Antoine Meyer, MD, PhD, 78 Rue du Général Leclerc, 94270 Le Kremlin-Bicêtre, France; e-mail, [email protected].
Author Contributions: Conception and design: F. Carbonnel, R. Dray-Spira, A. Meyer.
Analysis and interpretation of the data: F. Carbonnel, R. Dray-Spira, A. Meyer, A. Neumann, A. Weill.
Drafting of the article: A. Meyer.
Critical revision of the article for important intellectual content: F. Carbonnel, R. Dray-Spira, A. Meyer, A. Neumann, A. Weill.
Final approval of the article: F. Carbonnel, R. Dray-Spira, J. Drouin, A. Meyer, A. Neumann, A. Weill.
Statistical expertise: A. Meyer, A. Neumann.
Administrative, technical, or logistic support: A. Meyer.
Collection and assembly of data: J. Drouin, A. Meyer.
This article was published at Annals.org on 27 September 2022.

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Antoine Meyer, Anke Neumann, Jérôme Drouin, et al. Benefits and Risks Associated With Continuation of Anti–Tumor Necrosis Factor After 24 Weeks of Pregnancy in Women With Inflammatory Bowel Disease: A Nationwide Emulation Trial. Ann Intern Med.2022;175:1374-1382. [Epub 27 September 2022]. doi:10.7326/M22-0819

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