In pregnant women treated for inflammatory bowel diseases (IBD), infliximab and adalimumab, but not certolizumab, cross the placenta and are detected in infants up to 6 months after birth, according to the March issue of Clinical Gastroenterology and Hepatology (CGH). However, they do not appear to cause birth defects, and women who stop taking the drugs during pregnancy are able to start taking them again after delivery.
As therapeutic options for IBD increase, more patients are able to consider pregnancy. Yet it is not clear whether tumor necrosis factor (TNF) inhibitors are transferred to the fetus or cause complications during pregnancy. Two studies provide important new data about placental transfer of anti-TNF agents and their effects on the health of women and newborns.
Uma Mahadevan et al. studied serum concentrations of infliximab, adalimumab, and certolizumab pegol (a pegylated Fab fragment) in pregnant women, their newborn infants, and cord blood. Eleven women in the study had received infliximab during pregnancy, 10 received adalimumab, and 10 received certolizumab pegol.
Mahadevan et al. found that concentrations of infliximab and adalimumab, but not certolizumab pegol, were higher in newborns and cord blood than in their mothers.
Newborn levels of infliximab ranged from 2.9 to 39.5 μg/mL, and the drug was detectable for 2–7 months. None of the infants had birth defects or stays in the neonatal intensive care unit (NICU).
Newborns levels of adalimumab ranged from 4.28 to 17.7 μg/mL, and the drug was detectable for at least 11 weeks. None of the infants had birth defects, infections, or stays in the NICU; 1 had brief pulmonary edema at birth that resolved.
The median level of certolizumab pegol in the cord blood was 3.9% that of the mother (less than 2 μg/mL). The last dose was given a median of 19 days before delivery. The infants had no reported birth defects, infections, or stays in the NICU.
In a separate study, Zelinkova et al. investigated whether women who stopped taking anti-TNF agents during pregnancy had relapses of IBD, and whether they could be successfully reintroduced to anti-TNF therapy after they gave birth.
Pregnant women with IBD treated with infliximab or adalimumab stopped receiving the drugs before week 30. Twelve of 17 patients in remission on infliximab stopped therapy around week 23 and remained in remission for the rest of their pregnancies. All 11 patients taking adalimumab were in remission and stopped therapy around week 22; 2 patients had an IBD relapse.
The drugs were detected in cord blood of all but 1 neonate, whose mother had been treated with adalimumab. Women who restarted therapy in the post-partum period tolerated the reintroduction, except for 1 who experienced an allergic reaction after resuming infliximab 22 weeks post-partum. She was switched to adalimumab and achieved remission.
Despite the fact that 25% of the mothers had relapses of IBD during pregnancy, the authors conclude that discontinuation is safe for pregnant women, but does not completely eliminate drug exposure for newborns.
In an editorial that accompanies the articles, Sundanda Kane says that because disease activity can remit spontaneously during pregnancy, the risks and benefits of continuing therapy with conventional and biological agents need to be clarified. Additional prospective studies are needed to assess the risks of discontinuing therapy in pregnant women with mild disease, as well as the efficacy of restarting therapy.
Kane says that because infliximab and adalimumab will be present in the newborn and could take up to 6 or 7 months to clear, the recommendation to avoid live virus vaccines appears to be substantiated. Based on analyses of few breast milk samples collected by Zelinkova et al. it appears that infliximab is not transmitted in milk, so nursing should not be discouraged.
The Study of Pregnancy and Neonatal Outcomes in Women With Inflammatory Bowel Disease, which is underway, will collect more data on health of newborns and women taking medications used to manage IBD.
Read the articles online.
Mahadevan U , Wolf DC , Dubinsky M , et al. Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2013;11:286–292. This article has an accompanying continuing medical education activity and a podcast interview with the author.
Zelinkova Z , van der Ent C , Bruin KF , et al. Effects of discontinuing anti-tumor necrosis factor therapy during pregnancy on the course of inflammatory bowel disease and neonatal exposure. Clin Gastroenterol Hepatol 2013;11:318–321.
Read the accompanying editorial.
Kane S. Anti–tumor necrosis factor agents and placental transfer: relevant clinical data for rational decision-making. Clin Gastroenterol Hepatol 2013;11:293–294.