Safety of Tofacitinib for Treatment of Ulcerative Colitis, Based on 4.4 Years of Data From Global Clinical Trials

Abstract Background & Aims Tofacitinib is an oral, small-molecule inhibitor of JAK approved in several countries for the treatment of ulcerative colitis (UC). We report integrated safety analyses of tofacitinib-treated patients with moderate to severe UC. Methods Patients receiving placebo or tofacitinib (5 or 10 mg) twice daily were analyzed as 3 cohorts: induction (phase 2 and 3 induction studies, n=1220), maintenance (phase 3 maintenance study, n=592), and overall (patients receiving tofacitinib 5 or 10 mg twice daily in phase 2, phase 3, or open-label, long-term extension studies, n=1157; 1613 patient-years' exposure). Incidence rates (IRs; patients with events per 100 patient-years of exposure) were evaluated for select adverse events. Results In the maintenance cohort, IRs for select adverse events were similar among treatment groups, except for a numerically higher IR of herpes zoster infection among patients who received tofacitinib 5 mg twice daily (2.1; 95% CI, 0.4–6.0) and statistically higher IR among patients who received tofacitinib 10 mg twice daily (IR, 6.6; 95% CI, 3.2–12.2) vs placebo (IR, 1.0, 95% CI, 0.0–5.4). For the overall cohort (84% received average dose of tofacitinib 10 mg twice daily), IRs were: death, 0.2 (95% CI, 0.1–0.6); serious infections, 2.0 (95% CI, 1.4–2.8); opportunistic infections, 1.3 (95% CI, 0.8–2.0); herpes zoster infection, 4.1 (95% CI, 3.1–5.2); malignancy (excluding non-melanoma skin cancer), 0.7; 95% CI, 0.3–1.2); non-melanoma skin cancer, 0.7 (95% CI, 0.3–1.2); major adverse cardiovascular events, 0.2 (95% CI, 0.1–0.6); and gastrointestinal perforations, 0.2 (95% CI, 0.0–0.5). Conclusions In a safety analyses of patients with moderate to severe UC treated with tofacitinib, we observed a dose relationship with herpes zoster infection. Although follow-up time was relatively short, the safety profile of tofacitinib for patients with UC appeared similar to that reported for patients with rheumatoid arthritis and for patients with UC treated with biologic agents, except for the higher IR of herpes zoster infection. ClinicalTrials.gov, no: NCT00787202, NCT01465763, NCT01458951, NCT01458574, and NCT01470612.