First Selective Oral Jak1 Inhibitor Induces Remission in Ulcerative Colitis
Monika Fischer, MD, reviewing Sandborn WJ, et al. Gastroenterology 2020 Feb 21.
Upadacitinib, a selective Janus kinase 1 (Jak1) inhibitor (60-fold selective for Jak1 over Jak2 and >100-fold selective over Jak3), was designed to improve upon the efficacy-safety profile of nonselective counterparts. This phase 2b study included 250 patients with moderately to severely active ulcerative colitis who had previously failed or lost response to steroids, immunomodulators, and/or biologic therapy; this study showed dose-dependent response to upadacitinib. At week 8, the proportion of patients achieving clinical remission based on a once-daily dose of upadacitinib was 8.5% of patients in the 7.5-mg group, 14.3% in the 15-mg group, 13.5% in the 30-mg group, and 19.6% in the 45-mg group compared to 0% of the patients receiving placebo. Significantly higher proportions of patients receiving 15 mg, 30 mg, or 45 mg of upadacitinib (30.6%, 26.9%, and 35.7%, respectively) achieved endoscopic improvement (defined as an endoscopic subscore ≤1) compared to patients who received placebo. Clinical response to the drug was observed as early as week 2. Of the patients who received a daily dose of 45 mg, 1 patient developed herpes zoster and 1 patient had deep venous thrombosis and pulmonary embolism. Increases in serum lipid levels and creatine phosphokinase with upadacitinib were also observed.
Monika Fischer, MD, FASGE
CITATION(S )
Sandborn WJ, Ghosh S, Panes J, et al. Efficacy of upadacitinib in a randomized trial of patients with active ulcerative colitis. Gastroenterology 2020 Feb 21. (Epub ahead of print) (https://doi.org/10.1053/j.gastro.2020.02.030)