P956 Pregnancy outcomes after maternal or paternal exposure in the tofacitinib ulcerative colitis clinical programme

Abstract

Abstract Background Pregnant women with ulcerative colitis (UC) have a higher risk of adverse pregnancy outcomes vs age-matched controls.1 Tofacitinib is an oral Janus kinase inhibitor for the treatment of UC. There are no well-controlled studies on tofacitinib use in pregnant women. It was shown to be teratogenic in rats and rabbits at approximately 73 and 6.3 times, respectively, the maximum recommended human dose of 10 mg twice daily. Tofacitinib affects female fertility, parturition and peri/postnatal development in rats and was secreted into the milk of lactating rats; it had no effects on male fertility or sperm motility/concentration. Methods We report pregnancy outcomes in the tofacitinib UC clinical programme: 4 randomised, placebo-controlled Phase (P)2/3 studies (NCT00787202/NCT01465763/NCT01458951/NCT01458574),2,3 an open-label, long-term extension study (NCT01470612)4 and a randomised P3b/4 study (NCT03281304) were analysed.5 Study protocols excluded pregnant women, required females of childbearing potential to use effective contraception and regularly tested for urine β-hCG. Study drug was discontinued in female patients who became pregnant. Pregnancy outcomes after maternal or paternal tofacitinib exposure were identified from Pfizer’s internal safety database up to March 2023 and categorised as healthy newborn, medical termination, foetal death, congenital malformation, spontaneous abortion or lost to follow-up. Results There were 40 pregnancies with exposure to tofacitinib: 16 cases of maternal exposure (median age 29.5 [range: 24−41] years), all during the 1st trimester (10 [62.5%] healthy newborns, 2 [12.5%] medical terminations, 2 [12.5%] spontaneous abortions, 2 [12.5%] lost to followup); and 24 cases of paternal exposure (18 [75.0%] healthy newborns, 2 [8.3%] spontaneous abortions, 4 [16.7%] lost to follow-up). There were no cases of foetal death or congenital malformation. Conclusion Most known outcomes for maternal and paternal tofacitinib exposure were healthy newborns, similar to previous analyses in other tofacitinib clinical study populations and the general UC population.6,7 Limitations included the low number of reported pregnancies and available follow-up. Tofacitinib should not be used during pregnancy unless necessary.