Analysis of tofacitinib safety in ulcerative colitis from the completed global clinical developmental program up to 9.2 years of drug exposure

Background and Aims: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We report an integrated summary of tofacitinib safety from the completed global UC clinical program (9.2 years maximum tofacitinib exposure). Methods: This analysis included patients receiving tofacitinib 5 or 10 mg twice daily (b.i.d.) from completed phase 2/3 placebo-controlled studies, an open-label, long-term extension study and a randomized phase 3b/4 study. Proportions and incidence rates (IRs; unique patients with events/100 patient-years [PY] of exposure) were evaluated for deaths and adverse events (AEs) of special interest (AESI). Results: Overall, 1157 patients received ≥1 dose of tofacitinib 5 or 10 mg b.i.d.; 938 (81.1%) were in the predominant dose tofacitinib 10 mg b.i.d. group; 552 (47.7%) received tofacitinib for ≥2 years; total exposure: 3202.0 PY; 994 (85.9%) experienced AEs; 254 (22.0%) experienced serious AEs. Median treatment duration: 1.7 (range 0.0–9.2) years. IRs (95% CI) for combined tofacitinib doses: deaths 0.24 (0.10–0.48); serious infections (SIs) 1.80 (1.37–2.32); herpes zoster (HZ; non-serious and serious) 3.24 (2.63–3.94); serious HZ 0.24 (0.10–0.48); opportunistic infections 0.96 (0.65–1.36); malignancies (excluding non-melanoma skin cancer [NMSC]) 0.88 (0.59–1.26); NMSC 0.71 (0.45–1.07); major adverse cardiovascular events 0.27 (0.12–0.52); deep vein thrombosis 0.06 (0.01–0.22); pulmonary embolism 0.18 (0.07–0.40); and gastrointestinal perforations 0.09 (0.02–0.27). Conclusions: Except for HZ and SIs, IRs for AESI were <1 case/100 PY. Safety was consistent with previous analyses of shorter exposure and tofacitinib's known safety profile, including real-world data. ClinicalTrials.gov: NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612; NCT03281304.