Pregnancy Outcome in Women Treated With Adalimumab for the Treatment of Rheumatoid Arthritis: An Update on the OTIS Autoimmune Diseases in Pregnancy Project

Abstract

Introduction: To investigate pregnancy outcomes in women who received adalimumab (ADA) to treat rheumatoid arthritis (RA) during pregnancy. Methods: The OTIS collaborative research group conducted a prospective cohort study in the U.S. and Canada, 2004-2013, comparing pregnancy outcomes in women with RA treated with ADA to women with RA not treated with ADA. Participants may have been treated with another disease-modifying antirheumatic drug or steroid but not methotrexate. An additional comparison group included women without any autoimmune disease. Participants enrolled <19 weeks gestation and were followed by telephone interviews and medical record review. A subset of infants received a dysmorphological examination by a study physician. Outcomes were compared using regression or survival methods with adjustment for confounders. Results: Seventy-four ADA-exposed, 80 disease-matched and 218 non-diseased women were enrolled. Women in the ADA group had at least 1 dose in the first trimester; ˜43% used ADA in all trimesters. Disease severity was similar between the two diseased groups. The rates of major defects in the exposed, disease-matched, and non-diseased comparison groups were 5.6%, 7.8%, and 5.5% respectively. There was no significant difference in the rate of major malformations among live births in the ADA vs. disease-matched group (adjusted relative risk 1.14, 95% confidence interval [CI] 0.26, 4.93). Among those who received the dysmorphological examination, there were no differences in number with ≥3 minor malformations, and no specific pattern was identified. There was no significant difference in the risk of spontaneous abortion in the ADA vs. disease-matched groups (adjusted hazard ratio 1.96, 95% CI 0.47, 8.26); the rate was elevated in comparison to the non-diseased group (adjusted hazard ratio 3.79, 95% CI 1.01, 14.23), although the number of events was small. Rates of preterm delivery and small for gestational age were similar across groups. Conclusion: Pregnant women with RA treated with ADA in the first trimester compared to women with the same condition do not appear to be at increased risk of the adverse pregnancy outcomes evaluated. Although the sample size is small, these results are reassuring to pregnant women with RA who require treatment with ADA. AbbVie provided funding for this study and participated in the study design. AbbVie did not participate in study conduct, analysis, and interpretation of data. AbbVie had the opportunity to review and comment on the publication. All authors independently analyzed and interpreted the data, and authors maintained full control over the content of the publication. Disclosure - Research Grant Funding: Bristol Myers Squibb, La Roche, Genentech, CSL, Novartis, Amgen, Celgene, GSK, UCB, Eli, Protein Sciences, Abbott, TIS, Norvartis, Janseen, Sanofi Aventis, Pfizer. This research was supported by an industry grant from This research was supported by a grant from AbbVie Inc.