Efficacy and Safety of Upadacitinib in a Randomized Trial of Patients With Crohn’s Disease

Abstract Background & Aims We evaluated the efficacy and safety of upadacitinib, an oral selective Janus kinase 1 inhibitor, in a randomized trial of patients with Crohn’s disease (CD). Methods We performed a double-blind, phase 2 trial in adults with moderate to severe CD and inadequate response or intolerance to immunosuppressants or tumor necrosis factor antagonists. Patients were randomly assigned (1:1:1:1:1:1) to groups given placebo or 3 mg, 6 mg, 12 mg, or 24 mg upadacitinib twice daily, or 24 mg once daily, and evaluated by ileocolonoscopy at weeks 12 or 16 of the induction period. Patients who completed week 16 were re-randomized to a 36-week period of maintenance therapy with upadacitinib. The primary endpoints were clinical remission at week 16 and endoscopic remission at week 12 or 16 using multiple comparison procedure and modeling and the Cochran-Mantel-Haenszel test, with a 2-sided level of 10%. Results Among the 220 patients in the study, clinical remission was achieved by 13% of patients receiving 3 mg upadacitinib, 27% of patients receiving 6 mg upadacitinib (P Conclusions In a phase 2 trial of patients with CD, upadacitinib induced endoscopic remission in a significant proportion of patients, compared with placebo. Upadacitinib’s benefit–risk profile supports further development for treatment of CD. Clinicaltrials.gov ID no: NCT02365649