Efficacy of Upadacitinib in a Randomized Trial of Patients With Active Ulcerative Colitis.

BACKGROUND & AIMS We evaluated the efficacy and safety of upadacitinib, an oral selective inhibitor of Janus kinase 1, as induction therapy for ulcerative colitis (UC). METHODS We performed a multicenter, double-blind, phase 2b study of 250 adults with moderately to severely active UC and an inadequate response, loss of response, or intolerance to corticosteroids, immunosuppressive agents, and/or biologic therapies. Patients were randomly assigned to groups that received placebo or induction therapy with upadacitinib (7.5 mg, 15 mg, 30 mg, or 45 mg, extended release), once daily for 8 weeks. The primary endpoint was the proportion of subjects who achieve clinical remission according to the Adapted Mayo score at week 8. No multiplicity adjustments were applied. RESULTS At week 8, 8.5%, 14.3%, 13.5%, and 19.6% of patients receiving 7.5 mg, 15 mg, 30 mg, or 45 mg upadacitinib, respectively, achieved clinical remission compared with none of the patients receiving placebo (P = .052, P = .013, P = .011, and P = .002, compared with placebo, respectively). Endoscopic improvement at week 8, defined as endoscopic subscore ≤ 1, was achieved in 14.9%, 30.6%, 26.9%, and 35.7% of patients receiving upadacitinib 7.5 mg, 15 mg, 30 mg, or 45 mg, respectively compared with 2.2% receiving placebo (P = .033, P < .001, P < .001, P < .001, compared with placebo, respectively). One event of herpes zoster and 1 subject with pulmonary embolism and deep venous thrombosis (diagnosed 26 days after treatment discontinuation) were reported in the group that received upadacitinib 45 mg once daily. Increases in serum lipid levels and creatine phosphokinase with upadacitinib were observed. CONCLUSION In a phase 2b trial, 8 weeks treatment with upadacitinib was more effective than placebo for inducing remission in patients with moderately to severely active UC. ClinicalTrials.gov no: NCT02819635