644 Incidence of Venous Thromboembolic Events in Patients With Ulcerative Colitis Treated With Tofacitinib in the Ulcerative Colitis Clinical Development Program

Abstract

INTRODUCTION: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). A safety signal for pulmonary embolism (PE) was seen in the tofacitinib 10 mg twice daily (BID) arm of an FDA post-marketing requirement study in rheumatoid arthritis designed to evaluate the long-term risk of major cardiovascular events and malignancy. Patients (pts) eligible for this ongoing, open-label, safety-endpoint-driven study had to be ≥50 yrs of age, have ≥1 cardiovascular risk factor and be on a stable dose of methotrexate. UC is a known risk factor for deep vein thrombosis (DVT) and PE. 1,2 We report the incidence of DVT and PE in the tofacitinib UC clinical program, as of Sep 2018. METHODS: DVT and PE events were evaluated from 4 randomized placebo-controlled studies (Phase [P] 2 and P3 induction studies [NCT00787202; NCT01465763; NCT01458951], 1 maintenance P3 study [NCT01458574]), and an ongoing, open-label, long-term extension (OLE) study (NCT01470612). 3–5 Three cohorts were analyzed: Induction (P2/P3 induction studies), Maintenance (P3 maintenance study), and Overall (pts receiving tofacitinib 5 or 10 mg BID in P2, P3, or OLE studies). Incidence rates (unique pts with events per 100 pt-yrs [PY] of exposure) were evaluated. For Overall Cohort analysis, pts were categorized based on the average daily dose of tofacitinib: predominant dose (PD) tofacitinib 5 mg or 10 mg BID. RESULTS: 1157 pts were evaluated for DVT and PE, with 2404 PY of tofacitinib exposure and up to 6.1 yrs of treatment. In the Induction and Maintenance Cohorts, 2 pts had DVT and 2 had PE; all had received placebo in the study (Table 1). In the Overall Cohort, DVT occurred in 1 pt and PE in 4 pts during the OLE study; all pts had received PD of tofacitinib 10 mg BID. All pts with PE and DVT had risk factors for venous thrombosis (Table 1). CONCLUSION: In this post hoc analysis of pts with UC during tofacitinib exposure, 4 pts had PE and 1 pt had DVT, all of which occurred during the OLE study, in pts treated with PD of tofacitinib 10 mg BID (83% of Overall Cohort pts received a PD of tofacitinib 10 mg BID) with risk factors for venous thrombotic events. This analysis is limited by small sample size and limited drug exposure, and further study is needed.