Extended induction, maintenance with risankizumab efficacious in Crohn's

Last Updated: 2018-08-07

By Reuters Staff

NEW YORK (Reuters Health) - Risankizumab increases clinical response and maintains remission in patients with Crohn's disease, according to data from an extended phase 2 trial.

"Selective blockade of interleukin 23 warrants further investigation as a treatment for Crohn's disease," Dr. Brian Feagan of Robarts Clinical Trials in London, Ontario, and colleagues conclude in The Lancet Gastroenterology & Hepatology, online July 25.

Interleukin 23 has been implicated in the pathology of autoimmune disease, the authors note, while polymorphisms in the interleukin 23 receptor gene have been linked to Crohn's.

Risankizumab, which targets the p19 subunit of interleukin 23, is being investigated by Boehringer Ingelheim for treating psoriasis, psoratic arthritis and asthma in addition to Crohn's disease.

In the study's initial phase, 12 weeks of induction therapy with 600 mg of risankizumab every four weeks was shown to be more effective than placebo for inducing clinical and endoscopic remission in patients with moderate to severe Crohn's disease.

Patients who did not achieve deep remission at 12 weeks entered a second prespecified open-label induction. Six patients in deep remission took part in a 12-week washout period.

At week 26, 54 (53%) of 101 patients on induction treatment had achieved clinical remission. These patients, along with the six who had entered remission by 12 weeks, took part in an open-label maintenance phase, receiving 180 mg of risankizumab subcutaneously every eight weeks for another 26 weeks.

By one year, 44 patients (71%) were still in clinical remission, and 50 (81%) had a clinical response. Twenty-two (35%) were in endoscopic remission and 34 (55%) had an endoscopic response. Mucosal healing occurred in 15 patients (24%) and 18 (29%) were in deep remission.

The researchers observed no new safety signals in the trial extension.

"All patients in deep remission at week 12 who received no treatment in Period 2 remained in clinical remission at week 26," they write. "Larger phase 3 trials are ongoing, which will allow the assessment of predictors of clinical remission."

Average disease duration among the study participants was 14 years, and many had already been on at least one tumor necrosis factor inhibitor, Dr. Krisztina Gecse of the University of Amsterdam in the Netherlands notes in an editorial accompanying the study.

"However, a plateau of the dose-response curve was not shown in the 12-week induction study, suggesting that a higher induction dose might still increase efficacy," she writes.

"Several other molecules that selectively target the interleukin 23 pathway are in development, thus risankizumab may introduce a new era in the treatment of inflammatory bowel diseases," Dr. Gecse adds. "However, with our growing treatment armamentarium, it is of crucial importance to identify patients who are most likely to respond to these medications to achieve early, rapid, and long-term disease control."

Boehringer Ingelheim funded the study.

Dr. Feagan was not available for an interview by press time.

SOURCE: https://bit.ly/2LXqCT2 and https://bit.ly/2ALF1gb

Lancet Gastroenterol Hepatol 2018.