OP38 Tofacitinib for the treatment of Ulcerative Colitis: An integrated summary of safety data from the global OCTAVE and RIVETING clinical trials

Abstract

Abstract Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety of tofacitinib were evaluated in randomised, placebo-controlled Phase (P)2 (NCT00787202) and P3 (NCT01465763; NCT01458951; NCT01458574) studies, an open-label, long-term extension (OLE) study (NCT01470612) and an ongoing P3b/4 study (NCT03281304). We report updated tofacitinib safety analyses from the tofacitinib UC clinical programme, with inclusion of a 6-month interim analysis of data from the P3b/4 study, up to 7.8 years of tofacitinib exposure. Methods This analysis included 1157 patients (pts) receiving tofacitinib 5 or 10 mg BID from completed P2/P3/OLE studies, and the ongoing P3b/4 study (as of 20 Feb 2020; Overall+P3b/4 Cohort). Proportions and incidence rates (IRs; unique pts with events/100 pt-years [PY] of exposure) were evaluated for deaths and adverse events (AEs) of special interest. Opportunistic infections (OIs), malignancies, major adverse cardiovascular events (MACE) and gastrointestinal perforations were adjudicated. Results Table 1 shows demographics and clinical characteristics. In the Overall+P3b/4 Cohort, 1157 pts received ≥1 dose of tofacitinib 5 or 10 mg BID; 955 (83%) received a predominant dose of 10 mg BID; 397/1157 (34.3%) pts had received tofacitinib for >4.1 years. Median treatment duration was 623 (range, 1–2850) days (2999.7 PY of exposure). Table 2 shows safety data for AEs of special interest in the Overall+P3b/4 Cohort. IRs (95% confidence intervals) for all tofacitinib doses: deaths, 0.23 (0.09, 0.46); serious infections, 1.69 (1.26, 2.21); herpes zoster (non-serious and serious), 3.30 (2.67, 4.04); OIs, 1.03 (0.70, 1.46); malignancies (excluding non-melanoma skin cancer [NMSC]), 0.84 (0.55, 1.24); NMSC, 0.73 (0.45, 1.10); MACE, 0.29 (0.13, 0.55); deep vein thrombosis, 0.03 (0.00, 0.18); pulmonary embolism, 0.19 (0.07, 0.42); and gastrointestinal perforations, 0.10 (0.02, 0.28). IRs for AEs of special interest were similar to prior Overall Cohort analyses.1 Conclusion The safety profile of tofacitinib in pts with UC from the tofacitinib UC clinical programme was generally consistent with that of other UC therapies, including biologics, with the exception of herpes zoster.2 IRs for AEs of special interest have remained stable over an extended period of time (up to 7.8 years) with inclusion of final data from the OLE study and an interim analysis of data from the P3b/4 study.1,3