Risankizumab induces clinical remission in Crohn's disease

Last Updated: 2017-04-21

By Will Boggs MD

NEW YORK (Reuters Health) - The interleukin-23 inhibitor risankizumab induces clinical remission in patients with moderate-to-severe active Crohn's disease (CD), according to a phase 2 study.

"The most surprising result is that risankizumab showed a striking benefit in patients who had failed our best therapies for CD,” said Dr. Brian G. Feagan from Western University, Robarts Clinical Trials, in London, Canada.

“The endoscopic and deep-remission rates indicate that the drug has an important benefit in CD,” he told Reuters Health by email.

Risankizumab and other interleukin-23 inhibitors have shown efficacy in clinical trials for the treatment of psoriasis, but the role of interleukin-23 in CD remains unclear.

Dr. Feagan and colleagues investigated the safety and efficacy of risankizumab in a randomized placebo-controlled study of 121 patients with active CD (mean disease duration, 13 years).

Clinical-remission rates at week 12 were 24% (10/41) with risankizumab 200 mg, 37% (15/41) with risankizumab 600 mg, and 15% (6/39) with placebo. The clinical-remission rate was significantly better with risankizumab 600 mg than with placebo and was similar to that seen with infliximab or adalimumab.

Patients in the risankizumab 600 mg group were also more likely to experience clinical responses, endoscopic responses, or deep remissions at week 12, compared with patients in the placebo group, according to the report, online April 12 in The Lancet.

More patients in the risankizumab groups than in the placebo group had endoscopic remission at week 12, but mucosal healing rates did not differ among the groups.

Health-related quality of life improved from baseline to week 12 by 7.3 points for placebo, 21.7 points for 200 mg risankizumab, and 34.7 points for 600 mg risankizumab (only the latter was significantly different from placebo).

Both doses of risankizumab brought significant reductions in median C-reactive protein concentrations, whereas only the higher dose of risankizumab was associated with significantly lower median fecal calprotectin levels.

There were no dose-related increases for any adverse events associated with risankizumab treatment.

Treatment-emergent antidrug antibodies were detected in 4% of patients receiving risankizumab, although no neutralizing antibodies were detected.

“Risankizumab is a potential first-line biologic therapy for CD based upon the favorable therapeutic index in comparison to current treatments, such a TNF antagonists,” Dr. Feagan concluded. “It is also apparent that this is a very valuable agent for patients failing conventional treatments.”

Dr. Stephen B. Hanauer from Northwestern University Feinberg School of Medicine in Chicago, who wrote an accompanying editorial, told Reuters Health by email, "Unfortunately, because of the developmental route focusing on refractory moderate-severe disease, this will be the initial positioning. As I imply in my editorial, I believe that safe and effective therapies such as risankizumab should be used early in Crohn’s disease before other, ineffective or toxic therapies (steroids).”

“We need to change our drug development ‘culture’ in inflammatory bowel disease (IBD) to test these agents in earlier disease to prevent progression towards refractory, complicated disease,” he concluded.

Boehringer Ingelheim sponsored the trial, employed several authors and had various financial ties to others, including Dr. Feagan. Dr. Hanauer also reported having received consulting fees from Boehringer Ingelheim.

SOURCE: http://bit.ly/2pLCMmp and http://bit.ly/2pYRHpB

Lancet 2017.