Longterm Skyrizi Associated with Ulcerative Colitis Remission

Credit: Pexels / Taryn Elliott

Findings from a pair of clinical trials show risankizumab (Skyrizi) can help more patients achieve clinical remission from moderately to severely active ulcerative colitis (UC).

Data from the INSPIRE and COMMAND trials showed improved clinical UC remission rates with Skyrizi compared to placebo. The studies were the basis for the US Food and Drug Administration (FDA)'s approval of Skyrizi for the treatment of UC this last June.

“Despite numerous therapies, treating ulcerative colitis is often difficult because of the challenge of any one treatment achieving a highly efficacious and durable response over time,” Gilaad Kaplan, MD, MPH, a professor of professor of medicine in the department of medicine and community health sciences at Cumming School of Medicine at the University of Calgary, wrote at the time. “The absence of one clearly defining treatment for moderate to severe ulcerative colitis is, in part, the consequence of the multiple immunologic pathways involved in the pathogenesis of ulcerative colitis.”

Skyrizi is a biologic therapy approved by the FDA to additionally treat plaque psoriasis, psoriatic arthritis and Crohn’s disease. In the INSPIRE and COMMAND trials, participants were randomly assigned in a 2:1 ratio to receive either 1200 mg of Skyrizi or placebo administered intravenously at baseline, week four and eight, with randomization stratified by the presence of baseline corticosteroid use, baseline adapted Mayo score, and history of intolerance or inadequate response to advanced therapies.

The primary outcome of the INSPIRE study was clinical remission, determined using the adapted Mayo score and defined as a stool frequency score of one or less and not greater than baseline, rectal bleeding score of zero, and endoscopic subscore of one or less without friability at 12-week follow-up.¹

Of the 1430 patients screened for the induction trial, 977 were randomized and 975 received at least one dose of Skyrizi or placebo, administered intravenously. Among these patients, the mean age was 42.1 years old and the majority were male and White.

At week 12, clinical remission rates were 20.3 percent for participants receiving 1200 mg of Skyrizi and 6.2 percent for those receiving placebo. The most frequently reported adverse events were COVID-19 and anemia in the Skyrizi group, and colitis ulcerative and anemia in the placebo group.

Conducted at 238 clinical centers in 37 countries, the COMMAND trial enrolled patients who had been participated in the INSPIRE trial and had an adequate response to Skyrizi at the 12- or 24-week follow-up. Participants were randomly assigned in a 1:1:1 ratio to receive subcutaneous treatment with 180 mg or 360 mg of Skyrizi or placebo every eight weeks for 52 weeks, with randomization stratified by history of inadequate response to advanced therapy, last Skyrizi induction dose, and clinical remission status at the last visit of the induction trial.

Like the induction study, the primary outcome was clinical remission, determined using the adapted Mayo score and defined by components of the score at 52-week follow-up.

Of the 584 patients randomized in the maintenance trial, 548 had an adequate clinical response to Skyrizi at week 12 of the induction trial and were thus included in the primary efficacy population of the maintenance trial.

At week 52, the clinical remission rates were 40.2 percent for 180 mg Skyrizi, 37.6 percent for 360 mg Skyrizi, and 25.1 percent for placebo. The most frequently reported adverse events among all treatment groups were colitis ulcerative and COVID-19.

Investigators outlined multiple limitations to the findings from both INSPIRE and COMMAND, including the potential inflation of response rates during the maintenance trial due to continued Skyrizi exposure from the induction trial; the lack of evaluation of patients with prior exposure to emerging therapies in the evolving inflammatory bowel disease treatment landscape; and the need for follow-up beyond 52 weeks.

“Risankizumab adds to a growing list of biological drugs and oral small molecules that have proven efficacy in treating patients with moderate to severe ulcerative colitis. The challenge that gastroenterologists face is determining the sequence of these therapies for patients with ulcerative colitis,” Kaplan concluded. “Future comparative effectiveness clinical trials are needed to sequence risankizumab in the treatment paradigm of ulcerative colitis.”

An original version of this article was published on sister site HCPLive.