Tofacitinib for the treatment of ulcerative colitis: Up to 5.4 years of safety Da ta from global clinical trials

Background: Tofacitinib is an oral, small-molecule Janus kinase inhibitor approved in several countries for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib as UC induction and maintenance therapy were evaluated in Phase (P) 21 and P32 randomised, placebo-controlled studies, and in an ongoing, openlabel, long-term extension (OLE) study.3 We report up Da ted tofacitinib safety analyses from the UC programme, with exposure up to 5.4 years. Methods: Patients who received placebo, tofacitinib 5 or 10 mg twice Da ily (BID) were analysed as two cohorts: Maintenance (P3 maintenance, n = 592) and Overall (patients receiving tofacitinib 5 or 10 mg BID in P2, P3 or the OLE study, n = 1157; 2050.5 patientyears' exposure; Da ta at November 2017). Proportions and incidence rates (IR; unique patients with events per 100 patient-years) were evaluated for adverse events (AEs) of special interest. Opportunistic infections, malignancies, major adverse cardiovascular events (MACE) and gastrointestinal perforations were reviewed by independent adjudication committees. Results in the overall Ccohort based on the previous December 2016 Da ta cut are presented for context. Results: In total, 1157 patients received ≥1 dose of tofacitinib 5 or 10 mg BID. Demographics and disease characteristics were generally similar among treatment groups across cohorts. For the Overall Cohort, most patients (n = 956, 83%) received an average tofacitinib dose of 10 mg BID. IR for AEs of special interest were: death, 0.2; serious infection, 1.9; herpes zoster, 3.8; opportunistic infection, 1.2; malignancy (excluding non-melanoma skin cancer [NMSC]), 0.6; NMSC, 0.8; MACE, 0.3; and gastrointestinal perforation, 0.1. Conclusions: The safety profile of tofacitinib in patients with UC was manageable, and similar to the tofacitinib rheumatoid arthritis programme and that of other UC therapies including biologics. IR for AEs of special interest did not increase with longer exposure relative to previously reported analyses from the OCTAVE programme. A dose-dependent risk of herpes zoster was observed.