Is it safe to use biologic drugs in pregnancy?

Among the biologic drugs used during pregnancy, the most common is tumour necrosis factor-α antagonist (etanercept-infliximab-adalimumab), results of a clinical review have shown.

Additionally, eligible studies have shown no significant increase in teratogenic effects or adverse pregnancy outcomes, while exposure to adalimumab in pregnancy does not appear to increase the odds of adverse foetal or neonatal outcomes.

“These drugs can be used in severe uncontrolled immunological diseases and stopped during third trimester depending on each drug half-life,” said the researchers, led by Hesham Mahmoud from the Medway Maritime Hospital in Gilligham, UK.

Mahmoud and colleagues also noted that neonatal BCG vaccination must be delayed for 6 months after birth. They also reported the lack of safety data in newer biologics such as anakinra, abatacept, and tocilizumab to permit their use in pregnant women.

These findings were recently presented at RCOG 2023.

In this clinical review, the researchers accessed several databases and used the following keywords in their search: biologics, interleukin inhibitors, B cell inhibitors, etanercept, infliximab, adalimumab, tumour necrosis factor antagonists, and pregnancy. In total, 104 studies were identified, but only 17 were included in the review.

The biologic drugs assessed in the studies were tumour necrosis factor inhibitors, interleukin inhibitors, B cell inhibitors, and T cell inhibitors, which are used to treat ulcerative disease, Crohn’s disease, or rheumatoid arthritis. The most frequently used medications were etanercept, infliximab, adalimumab, and certolizumab. [RCOG 2023, abstract PP.0070]

Pregnancy outcomes

In a large uncontrolled observational study, use of infliximab (n=1,850) during pregnancy did not result in significant differences in congenital anomalies or neonatal infection with low-birth-weight infant (3.6 percent), congenital anomalies (2.0 percent), and infant infections (1.2 percent).

Likewise, no serious neonatal complication was observed in a multicentre cross-sectional study on pregnancy exposure to infliximab (n=32) and adalimumab (n=9). Infliximab cord levels measured in 11 children were positively associated with maternal levels at delivery, but no such relationship was seen in the case of adalimumab.

In a retrospective study in Japan involving 74 maternal exposures to adalimumab (2008‒2017), any risk to pregnancy outcomes was not reported. Another study of 602 pregnancies with adalimumab exposure showed no increase in adverse maternal or foetal outcomes.

Finally, 300 pregnant women identified using a Canadian Registry and who were treated with infliximab did not experience increased foetal or neonatal infection risks in the first year of life. In addition, immune responses to vaccines were normal.

These findings were consistent with those of a recent systematic review and meta-analysis, which found similar adverse pregnancy outcomes among pregnant women using biologic drugs with that of the general population. [Clin Gastroenterol Hepatol 2022;20:74-87.e3]

“Biologics are groups of drugs that target specific inflammatory cytokines pathways. They are used in inflammatory diseases that widely affect pregnant women,” according to the researchers. “Most of them are insufficiently tested for their adverse maternal and neonatal effects.”