FDA Approves Upadacitinib for Moderately to Severely Active Ulcerative Colitis

The FDA has approved upadacitinib (Rinvoq; AbbVie) for the treatment of adults with moderately to severely active ulcerative colitiswho have had an inadequate response or intolerance to 1 or more tumor necrosis factor (TNF) blockers.

The action represents the first approval for upadacitinib in the field of gastroenterology. The approval was based on 3 randomized, double-blind, placebo-controlled phase 3 clinical trials. These included the U-ACHIEVE and U-ACCOMPLISH induction studies, in which upadacitinib was evaluated at 45 mg once daily for 8 weeks, followed by 15 mg or 30 mg once daily in the maintenance trial for 52 weeks.

The investigators found that patients treated with upadacitinib achieved clinical remission more frequently through weeks 8 and 52 versus the placebo group. The primary endpoint of the study was stool frequency subscore (SFS) ≤ 1 and not greater than baseline, rectal bleeding subscore (RBS) = 0, and endoscopy subscore (ES) of ≤ 1 without friability.

During the U-ACHIEVE and U-ACCOMPLISH induction trials at week 8, 26% and 33% of patients treated with upadacitinib 45 mg achieved clinical remission compared to 5% and 4% of patients administered placebo. Onset of response was observed as early as week 2, with a greater proportion of patients administered upadacitinib 45 mg once daily achieving clinical response, defined as a decrease of ≥1 point and ≥30 percent from baseline and a reduction in RBS of ≥1 or an absolute RBS ≤1 per the pmMS, compared to placebo.

Further, upadacitinib achieved all ranked secondary endpoints, including endoscopic improvement and histologic-endoscopic mucosal improvement, as well as corticosteroid-free clinical remission.

During the maintenance trial, 42% and 52% of patients administered upadacitinib 15 mg or 30 mg, respectively, achieved clinical remission at week 52 versus 12% of patients in the placebo group.

The study also found that 57% and 68% of patients administered upadacitinib 15 mg or 30 mg, respectively, achieved corticosteroid-free remission, defined as clinical remission (per mMS) and corticosteroid-free for ≥90 days immediately preceding week 52 in patients who achieved clinical remission at the end of the induction treatment, versus 22% of patients on placebo.

"Ulcerative colitis patients live with unpredictable symptoms such as increased stool frequency and bleeding, which can make daily activities difficult," said Maria T. Abreu, MD, Professor of Medicine, Professor of Microbiology and Immunology, University of Miami Miller School of Medicine and Director, Crohn's & Colitis Center, University of Miami Health System, in a press release. "In clinical trials, Rinvoq showed its ability to rapidly control symptoms in just eight weeks for many patients and sustained responses at one year. I believe these types of improvements can make a positive difference for my patients."

Reference

RINVOQ® (upadacitinib) Receives FDA Approval for the Treatment of Adults with Moderately to Severely Active Ulcerative Colitis. AbbVie. [news release]. March 16, 2022. https://news.abbvie.com/news/press-releases/rinvoq-upadacitinib-receives-fda-approval-for-treatment-adults-with-moderately-to-severely-active-ulcerative-colitis.htm