S0644 Tofacitinib for the Treatment of Ulcerative Colitis: An Updated Analysis of Infection Rates in the Tofacitinib Ulcerative Colitis Clinical Program

Abstract

INTRODUCTION: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. We present updated infections data from the tofacitinib UC clinical program (1), as of May 2019. METHODS: Infection events were evaluated in a Phase (P)2 induction study (NCT00787202), 2 P3 induction studies (NCT01465763; NCT01458951), a P3 maintenance study (NCT01458574), and an ongoing, open-label, long-term extension (OLE) study (NCT01470612) as 3 cohorts: Induction (P2 and P3; placebo [PBO] or tofacitinib 10 mg twice daily [BID]), Maintenance (P3; PBO, tofacitinib 5 or 10 mg BID), and Overall (all patients [pts] receiving tofacitinib 5 or 10 mg BID in P2/P3/OLE studies; by predominant dose [5 or 10 mg BID based on average daily dose < 15 mg or ≥ 15 mg, respectively]; as of May 2019, database not locked). Proportions and incidence rates (IRs; unique pts with events per 100 pt-years [PY] of exposure; censored at time of event) were evaluated for infections, serious infections (SIs), opportunistic infections (OIs; independently adjudicated, incl. non-herpes zoster [HZ] OIs), and HZ. RESULTS: 1,157 pts received ≥ 1 dose of tofacitinib 5 or 10 mg BID (83% predominantly 10 mg BID), with 2,581.3 PY of exposure (up to 6.8 years). Nasopharyngitis was the most frequent infection in the Overall Cohort (251 pts; 21.7%). In induction, SIs and OIs were numerically higher with tofacitinib vs PBO (Table 1). The Overall Cohort SI IR was 1.70, which was generally similar to Maintenance Cohort IRs for tofacitinib 5 and 10 mg BID and PBO, and the Overall Cohort IR (1.75) in the previous report. No SIs resulted in death. OIs were infrequent (28 pts; IR 1.07), and most OIs were HZ (24 pts; IR 0.92; mostly cutaneous). Overall, 87 pts had HZ (non-serious and serious; IR 3.48 [95% CI 2.79, 4.30]); 7 serious. Maintenance Cohort HZ IR was numerically higher for tofacitinib 10 vs 5 mg BID, but with overlapping 95% CIs; Overall Cohort HZ IRs were similar between doses. CONCLUSION: Overall, SIs were generally infrequent, and similar (indirectly) to other UC therapies, incl. biologics (2). In induction, SIs and OIs were more frequent with tofacitinib vs PBO. In the Maintenance Cohort, HZ IR was numerically higher with tofacitinib 10 vs 5 mg BID. Over time in the Overall Cohort, IRs were similar between doses and remained stable vs the previous data cut (1). Non-HZ OIs and viral infections were rare.Table 1