Upadacitinib Superior to Placebo For Moderately to Severely Active Crohn Disease

According to the results of a session presented at The American College of Gastroenterology 2022 Annual Scientific Meeting in Charlotte, NC, upadacitinib, an oral, reversible Janus kinase inhibitor, is superior to placebo for all clinical and endoscopic outcomes at 52 weeks among patients with moderate-to-severe Crohn disease who respond to upadacitinib induction therapy.

Prior to the current randomized Phase 3 U-ENDURE maintenance study, U-EXCEL and U-EXCEED phase 3, double-blind, placebo-controlled trials evaluated the efficacy and safety of upadacitinib as induction therapy in patients with moderately to severely active Crohn disease. In those trials, the authors found that 45 mg of upadacitinib once daily for 12 weeks was effective in inducing clinical and endoscopic improvements and had an acceptable safety profile.

In the subsequent Phase 3 U-ENDURE maintenance study, researchers evaluated the efficacy and safety of both 15 mg of upadacitinib once daily and 30 mg once daily in patients with Crohn disease at 52 weeks. Patients who responded to 45 mg of upadacitinib once daily over 12 weeks in one of the induction studies (>30% decrease average daily very soft/liquid stool frequency [SF] and/or average daily abdominal pain score [APS]) were eligible for the U-ENDURE trial.

At week 12, patients were randomized (1:1:1) to 15 mg once daily (n = 169), 30 mg once daily (n=168), or placebo (n = 165) for 52 weeks of maintenance therapy. The study’s primary endpoints were clinical remission per Crohn disease activity index or SF. Endoscopic response was also evaluated at week 52, while upadacitinib’s safety profile was evaluated at or through 52 weeks.

According to the study results, 40.1% of patients treated with 30 mg of upadacitinib achieved endoscopic clinical response compared with 27.6% of patients treated with 15 mg and those treated with placebo (7.3%). Further, at week 52, a greater proportion of patients receiving 15 mg of upadacitinib (37.3%) and 30 mg of upadacitinib (47.6%) achieved clinical remission per the Crohn disease activity index compared with the placebo group (15.1%) and per SF and APS (35.5% and 46.4% vs 14.4%, respectively.) Additionally, the rates of adverse events (AE) and serious AEs were similar across upadacitinib groups.

“Among patients with moderate-to-severe active Crohn disease who responded to upadacitinib induction therapy, maintenance treatment with 15 mg of upadacitinib once daily or 30 mg of upadacitinib once daily was superior to placebo for all clinical and endoscopic outcomes at 52 weeks,” the authors concluded.

—Anthony Calabro

Reference:

Panes J, Loftus Jr EV, Lacerda A, et al. Efficacy and safety of upadacitinib maintenance therapy in patients with moderately to severely active Crohn’s disease: results from a randomized phase 3 U-ENDURE maintenance study. Presented at ACG 2022; October 21-26; Charlotte, NC. Accessed October 19, 2022. https://acgmeetings.gi.org/