Induction therapy with upadacitinib, an oral Janus kinase 1 selective inhibitor, was more efficacious for inducing remission in patients with active ulcerative colitis (UC) compared with placebo, according to results published in Gastroenterology.
In this phase 2b, international, multicenter, placebo-controlled, double-blind, randomized study conducted from October 2016 to April 2018 (ClinicalTrials.gov Identifier: NCT02819635), which is part of the U-ACHIEVE program for difficult-to-treat UC, Sandborn and colleagues evaluated the efficacy and safety of upadacitinib for adult patients with moderately to severely active UC and an inadequate response, loss of response, or intolerance to corticosteroids, immunosuppressive agents, and/or biologic therapies for 8 weeks of induction therapy.
In total, 250 patients were randomly assigned (1:1:1:1:1) to receive once-daily, oral upadacitinib (7.5 mg, n=47; 15 mg, n=49; 30 mg, n=52, or 45 mg, n=56) or placebo (n=46) for 8 weeks. The primary endpoint was the proportion of participants who achieved clinical remission at week 8 (Adapted Mayo score).
Patients had a median disease duration of 5.92 years. More than half of the patients (54%) had pancolitis, and over one-third (36.1%) of the patients had a baseline Adapted Mayo Score >7. Approximately three-fourths of the patients (73.2%) had previously received a tumor necrosis factor antagonist.
After 8 weeks of therapy, all of the patient groups receiving upadacitinib (7.5 mg, 15 mg, 30 mg, and 45 mg) achieved significantly higher proportions of clinical remission (8.5%, 14.3%, 13.5%, and 19.6%, respectively) compared with the placebo group (placebo, 0%; P =.052, P =.013, P =.011, and P =.002, respectively).
Similarly, all of the patient groups receiving upadacitinib (7.5 mg, 15 mg, 30 mg, and 45 mg) achieved significantly higher proportions of endoscopic improvement (endoscopic subscore ≤1; 14.9%, 30.6%, 26.9%, and 35.7%, respectively) compared with the placebo group (placebo, 2.2%; P =.033, P <.001, P <.001, and P <.001, respectively).
Of 227 subjects, 90.8% completed the study. The induction therapy with upadacitinib was well tolerated. The most common reasons for discontinuation of upadacitinib were adverse events (5.6%) and lack of efficacy (2.8%). The rate of serious adverse events was higher in the placebo group (10.9%) than in the upadacitinib groups (7.5 mg, 0%; 15 mg, 4.1%; 30 mg, 5.8%; and 45 mg, 5.4%). In the 45 mg group, herpes zoster (n=1) and embolism and deep venous thrombosis (n=1) were reported.
Limitations of the study included limited sample size and exposure time to upadacitinib; no adjustments were made for multiple testing or secondary endpoints.
“The benefit-risk profile supports further development of upadacitinib as a novel treatment for ulcerative colitis,” concluded the authors.
Disclosure: This clinical trial was supported by AbbVie Inc. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Sandborn WJ, Ghosh S, Panes J, et al. Efficacy of upadacitinib in a randomized trial of patients with active ulcerative colitis [published online February 21, 2020]. Gastroenterology. doi: 10.1053/j.gastro.2020.02.030