Dr Loftus reviews results from the phase 3 INSPIRE trial of risankizumab for induction of remission among patients with moderate to severe ulcerative colitis.

Edward V. Loftus, Jr., M.D. is the Maxine and Jack Zarrow Family Professor of Gastroenterology Specifically in IBD at the Mayo Clinic College of Medicine and Science in Rochester, Minnesota.

TRANSCRIPT:

Ed Loftus:

Hi, I'm Ed Loftus. I'm a professor of medicine at Mayo Clinic and I'm here in Vancouver at ACG. And earlier today I had an oral presentation of the phase 3 INSPIRE study, which was a study of risankizumab as induction therapy for patients with moderate to severe ulcerative colitis. So as you may know, risankizumab is an anti-IL-23 monoclonal antibody. It's humanized. It's been studied in psoriasis, Crohn's disease, and now ulcerative colitis.

This was a large phase 3 trial, almost 1,000 patients. They had moderate to severely active ulcerative colitis. They could not have previously been on ustekinumab or other IL-23, but they were permitted to have failed other biologic agents or conventional therapy. And so this, again, patients were randomized 2 to 1 to either risankizumab, 1,200 mg every 4 weeks for 3 doses, or placebo. And then they were assessed at week 12 for clinical remission using a standard Mayo Clinic score-based endpoint.

And that was basically defined as a stool frequency score of 0 or 1, a rectal bleeding score of 0 and a Mayo endoscopic subscore of 0 or 1. And then there were a variety of secondary endpoints that were also studied. And so about 98% of the patients in risankizumab completed the study, 92% in placebo. The primary endpoint was met, so this was significantly higher in the risankizumab treated patients, and the delta overall was about 14% between the 2 treatment arms. If you stratify those results by whether or not they had failed advanced therapies, it was 21% in the advanced therapy naive group, and it was 7% in the patients who had failed advanced therapies.

In terms of secondary endpoints, all the prespecified secondary endpoints were met, and that included clinical response at week 4, clinical response at week 12, endoscopic improvement, endoscopic remission, histoendoscopic mucosal improvement, histoendoscopic mucosal remission, and then a variety of patient reported outcomes were met, including no bowel urgency, no abdominal pain, and no nocturnal bowel movements. So overall, pretty good results.

Hospitalizations also 5.5% on placebo, less than 1% in risankizumab treated patients over 12 weeks. Safety looked pretty good. There was one death in the risankizumab group, a patient who died from COVID-19 pneumonia. There were no malignancies, no MACE events or major adverse cardiovascular events. There were a smattering of serious infections, but numerically lower in the patients treated with risankizumab. A couple of zoster cases, none of them were serious. There were actually numerically fewer LFT issues in risankizumab compared to placebo. So overall, pretty good results. No malignancies in risankizumab treated group.

And so the conclusion was that this appeared to be an efficacious drug, also safe, and we look forward to seeing the maintenance data at some point in the near future, within the next, say, 6 to 12 months. So great option to have in our tough to treat IBD patients.