PREGNANCY OUTCOMES AFTER MATERNAL OR PATERNAL EXPOSURE IN THE TOFACITINIB ULCERATIVE COLITIS CLINICAL PROGRAM

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 program: 4 randomized, placebo-controlled Phase (P)2/3 studies (NCT00787202/NCT01465763/NCT01458951/NCT01458574),^2,3 an open-label, long-term extension study (NCT01470612),⁴ and a randomized P3b/4 study (NCT03281304) were analyzed.⁵ Study protocols excluded pregnant women and required females of childbearing potential to use effective contraception and be 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 categorized as healthy newborn, medical termination, fetal 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 1^st trimester (10 [62.5%] healthy newborns, 2 [12.5%] medical terminations, 2 [12.5%] spontaneous abortions, 2 [12.5%] lost to follow-up); 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 fetal 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.

References:
1. Cornish et al. Gut 2007;56:830−7
2. Sandborn et al. N Engl J Med 2012;367:616−24
3. Sandborn et al. N Engl J Med 2017;376:1723−36
4. Sandborn et al. Aliment Pharmacol Ther 2022;55:464–78
5. Vermeire et al. J Crohns Colitis 2021;15:1130–41
6. Mahadevan et al. Inflamm Bowel Dis 2018;24:2494–500
7. Selinger et al. Frontline Gastroenterol 2021;12:214–24

Study sponsored by Pfizer. Medical writing support funded by Pfizer: S Leneghan, CMC Connect