Edward V Loftus, Jr, MD: Discussing FDA Approval of Risankizumab (Skyrizi) in Ulcerative Colitis

The recent US Food and Drug Administration (FDA) approval of risankizumab-rzaa (Skyrizi) for adults with moderately to severely active ulcerative colitis (UC) made it the first interleukin (IL)-23 specific inhibitor approved for both UC and Crohn's disease (CD).¹

The decision, announced on June 18, 2024, was based on data from a pair of phase 3 clinical trials: a 12-week induction study, INSPIRE, and a 52-week maintenance study, COMMAND. Findings showed clinical remission, the primary endpoint in both studies, was achieved, along with endoscopic improvement, a key secondary endpoint.¹

An IL-23 inhibitor that selectively blocks IL-23 by binding to its p19 subunit, risankizumab’s approval in UC adds to its growing number of approved indications across immune-mediated inflammatory diseases, including plaque psoriasis, psoriatic arthritis, and CD.¹

“It turns out that interleukin 23 is an important messenger in the whole inflammatory pathway,” Edward V Loftus, Jr, MD, Maxine and Jack Zarrow family professor of gastroenterology in the division of gastroenterology and hepatology at Mayo Clinic, explained to HCPLive. “We've learned that what we call the Th17, or T-helper 17, pathway, is important in chronic inflammation of the bowel. By blocking IL-23, you actually shut down a lot of that Th17 pathway.”

The FDA approval of risankizumab in UC was based on findings from a pair of phase 3 studies, INSPIRE and COMMAND, demonstrating its ability to induce clinical remission, endoscopic improvement, and histologic endoscopic mucosal improvement.¹

“Another novel endpoint that was studied that was positive was in the maintenance study that could actually show a decrease in the number of ulcerative colitis related hospitalizations during the course of the study compared to the placebo group,” Loftus added, mentioning the lack of safety concerns associated with IL-23s as one of the “nice features” of risankizumab because “there's not a lot of baggage with it.”

Indeed, safety results from both INSPIRE and COMMAND remained consistent with previous trial data, with no new safety risks observed. In INSPIRE, the most common adverse events observed in the risankizumab group were COVID-19, anemia, and arthralgia. In COMMAND, they were COVID-19, nasopharyngitis, and arthralgia.²

“In a complex world, even providers like to have simple algorithms, so this might be simple to say ‘Okay, I know this one is approved for both [ulcerative colitis and Crohn’s disease]’ and so you might be more likely to use it,” Loftus concluded.

References:

1. ^{Brooks, A. FDA Approves Risankizumab (Skyrizi) for Ulcerative Colitis. HCPLive. June 18, 2024. Accessed June 21, 2024. https://www.hcplive.com/view/fda-approves-risankizumab-skyrizi-for-ulcerative-colitis}
2. ^{Brooks, A. AbbVie Submits Application to FDA for Risankizumab in Ulcerative Colitis. HCPLive. August 28, 2023. Accessed June 21, 2024. https://www.hcplive.com/view/abbvie-submits-application-to-fda-for-risankizumab-in-ulcerative-colitis}