Adalimumab (Humira, AbbVie) exposure in pregnancy is not associated with an increased risk for major and minor structural birth defects, spontaneous abortion, pre and post-natal growth deficiency, serious or opportunistic infections and malignancies, say researchers writing in PLOS ONE this month.
The study also confirmed that women with rheumatoid arthritis or Crohn’s disease were at increased risk of preterm delivery, irrespective of adalimumab exposure.
Adalimumab, an anti-tumor necrosis factor alpha (anti-TNF-α) therapy, is approved for the treatment of rheumatoid arthritis and Crohn's disease, along with a number of other chronic inflammatory diseases, many of which are prevalent in women of child-bearing age. Hence evaluation of the safety of anti-TNF-α therapies used in pregnancy is needed. Adalimumab is a fully humanized monoclonal antibody with a high molecular weight and is expected to require active transport in order to cross the placenta. Accordingly, it is believed that potential exposure of the embryo via placental transfer is limited earlier in pregnancy, while transfer to the fetus later in pregnancy has been reported.
There are limited data regarding the fetal safety of adalimumab when used in pregnancy. Results from two previous studies suggest that the underlying maternal inflammatory diseases may play a role in birth outcomes in women treated with anti-TNF-α medication in pregnancy.
“No study to date has comprehensively examined the range of pregnancy outcomes among pregnancies specifically exposed to adalimumab compared to disease-matched and healthy women without the same chronic inflammatory diseases,” wrote the authors, led by Christina D. Chambers, Ph.D., M.P.H., of the University of California San Diego in California.
This U.S. and Canada-wide cohort study included of 602 mothers, of which 257 had received adalimumab in the first trimester for the treatment of rheumatoid arthritis or Crohn's disease, 120 had rheumatoid arthritis or Crohn's disease but had not been not exposed to adalimumab, and 225 had no rheumatic or inflammatory bowel diseases. The birth prevalence and patterns of major and minor structural birth defects, spontaneous abortion, preterm birth, pre- and postnatal growth deficiency, and risks for serious or opportunistic infections or malignancies in the infants were evaluated.
Women and their infants were followed to one year postpartum and 7 percent of pregnancies were lost-to-follow-up. In the adalimumab-exposed group, 10 percent had a live born infant with a major birth defect compared to 7.5 percent of the unexposed mothers with rheumatoid arthritis or Crohn's disease, a finding which was non-significant. Meanwhile, the birth prevalence of major birth defects in live births was 6.1 percent in the healthy comparison group, which is higher than the 3 percent to 5 percent general population rates. “It is possible that erring on the side of caution in careful abstraction of medical records over the first year of life, as is typical in pregnancy registries, led to identification of more defects,” the authors wrote.
Among the major structural birth defects identified in the adalimumab-exposed group, there was no evidence of a consistent pattern.
Women exposed to adalimumab were more likely to deliver preterm compared to the healthy group (adjusted hazard ratio [aHR] 2.59, 95% CI 1.22 to 5.50), but not compared to the unexposed women with rheumatoid arthritis or Crohn's disease (aHR 0.82, 95% CI 0.66 to 7.20). No significant increased risks were found with adalimumab exposure for any other study outcomes.
“There was evidence of an approximate doubling of risk for preterm delivery in adalimumab-exposed but only in comparison to the healthy unexposed women.
“This isolated finding is consistent with several previous studies in women with rheumatoid arthritis or Crohn’s Disease, suggesting that the diseases themselves contribute to the risk of early delivery,” the authors wrote.
Although the study found no significant increases in spontaneous abortion in any comparison, women enrolled in the study on average at the end of the first trimester, so spontaneous abortion in the early weeks of gestation when the risk is highest was not assessed.
Christina D. Chambers ,Diana L. Johnson, Ronghui Xu, et al. “Birth outcomes in women who have taken adalimumab in pregnancy: A prospective cohort study.” PLoS One. October 18, 2019. doi: 10.1371/journal.pone.0223603.