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.
COMMENT
This is the first randomized controlled trial evaluating a selective Jak1 inhibitor in ulcerative colitis. In this study, more stringent criteria were used to evaluate clinical remission (adapted Mayo score); therefore, efficacy results are comparable to tofacitinib, a nonselective Jak inhibitor.Regarding safety, the same type of adverse events associated with tofacitinib were observed here with upadacitinib. Whether the frequency of these adverse events is lower with upadacitinib will need to be addressed in phase 3 trials.
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)
