While the majority of known outcomes for maternal and paternal tofacitinib exposure resulted in healthy newborns, further research with larger sample sizes and longer follow-up periods is warranted to fully understand the safety profile of tofacitinib during pregnancy, according to a poster presentation by Uma Mahadevan, MD, at Digestive Disease Week in Washington, DC, on May 20.

Dr Mahadevan is a professor of medicine and director of the Center for Colitis and Crohn’s Disease at the University of California San Francisco. is a professor of medicine and director of the Center for Colitis and Crohn’s Disease at the University of California San Francisco. She is also the principal investigator of the Pregnancy Inflammatory bowel disease And Neonatal Outcomes (PIANO) study, a national registry of women with IBD and their children that reviews the safety of IBD medications on pregnancy and short- and long-term outcomes of the children.

“Pregnancy Outcomes After Maternal or Paternal Exposure in The Tofacitinib Ulcerative Colitis Clinical Program” aimed to assess pregnancy outcomes in women with ulcerative colitis (UC) exposed to tofacitinib, an oral Janus kinase inhibitor, through analysis of data from multiple clinical trials. Despite evidence suggesting higher risks of adverse pregnancy outcomes in pregnant women with UC, tofacitinib's safety profile during pregnancy remained uncertain due to the lack of well-controlled studies.

Results from the analysis of 4 randomized, placebo-controlled Phase 2/3 studies, an open-label long-term extension study, and a randomized Phase 3b/4 study revealed 40 pregnancies with exposure to tofacitinib. Maternal exposure occurred during the first trimester in all cases, resulting in 10 healthy newborns, 2 medical terminations, 2 spontaneous abortions, and 2 cases lost to follow-up. Paternal exposure led to 18 healthy newborns, 2 spontaneous abortions, and 4 cases lost to follow-up. Notably, there were no instances of fetal death or congenital malformation reported.

The findings suggest that most pregnancy outcomes following maternal or paternal tofacitinib exposure were favorable, aligning with previous analyses in other tofacitinib clinical study populations and the general UC population. However, Dr Mahadevan acknowledged limitations of the study, such as the small number of reported pregnancies and limited follow-up data. As tofacitinib was shown to be teratogenic in animal studies, caution is advised regarding its use during pregnancy unless deemed necessary.

Reference
Mahadevan U, Chaparro M, Segovia M, Kulisek N, et al. Pregnancy outcomes after maternal or paternal exposure in the tofacitinib ulcerative colitis clinical program. Poster presented at: Digestive Disease Week; May 18–21, 2024; Washington, DC.