S0847 Pregnancy Outcomes in the Tofacitinib Ulcerative Colitis OCTAVE Studies: An Update as of February 2020

INTRODUCTION: Pregnant women with UC have a higher risk of adverse pregnancy outcomes compared with age-matched controls [1]. Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. In rats and rabbits, tofacitinib exhibits teratogenic effects at 146 and 13 times, respectively, the human dose of 5 mg twice daily. There are no adequately sized, well-controlled studies of tofacitinib in pregnant women. METHODS: We report updated pregnancy outcomes [2] from 3 randomized, placebo-controlled studies (OCTAVE Induction 1&2: NCT01465763, NCT01458951; OCTAVE Sustain: NCT01458574) and an ongoing, open-label, long-term extension study (OCTAVE Open: NCT01470612) of tofacitinib in patients (pts) with moderately to severely active UC [3,4]. Pregnancy outcomes following maternal or paternal exposure to tofacitinib were identified from Pfizer’s internal safety database up to Feb 11, 2020, and categorized as healthy newborn, medical termination, fetal death, congenital malformation, spontaneous abortion, or lost to follow-up. Trial protocols required females of childbearing potential to use highly effective contraception, and included regular urine β-hCG testing. The study drug was discontinued in pts who became pregnant. RESULTS: The UC OCTAVE trials included 1,139 unique pts (including placebo), of whom 296 were females of childbearing age. A total of 34 pregnancies with exposure to tofacitinib were reported. Of these, 15 were cases of maternal exposure, all during the 1st trimester: 9 (60.0%) healthy newborns, 2 (13.3%) medical terminations, 2 (13.3%) spontaneous abortions, and 2 (13.3%) cases lost to follow-up. There were 19 cases of paternal exposure: 15 (78.9%) healthy newborns, 2 (10.5%) spontaneous abortions, and 2 (10.5%) cases lost to follow-up. There were no cases of fetal death or congenital malformation. CONCLUSION: The majority of known outcomes for both maternal and paternal cases were healthy newborns. Although there are limited data and follow-up available, this analysis was consistent with a previous analysis in pts with UC [2], as well as an analysis in pts with rheumatoid arthritis and psoriasis [5]. Tofacitinib should not be used during pregnancy unless clearly necessary.