In active Crohn disease, risankizumab increased clinical remission and endoscopic response at 12 wk
While the FDA has now approved risankizumab for adults with moderate to severe Crohn disease, understanding of the drug's role in relation to other biologic therapies is limited by broad exclusion criteria in randomized controlled trials, an ACP Journal Club commentary noted.
In the industry-funded ADVANCE and MOTIVATE phase 3 randomized controlled trials (RCTs), IV risankizumab (600 or 1,200 mg) increased clinical remission and endoscopic response compared to placebo in patients with moderately to severely active Crohn disease. The drug appeared to be well tolerated, with few adverse events during follow-up after induction therapy.
Results from the trials were published May 28 by The Lancet. The following commentary by Daniel Oliver, MD, and Nicholas J. Talley, MD, PhD, FACP, was published in the ACP Journal Club section of the October Annals of Internal Medicine.
Multiple cytokines are implicated in the pathogenesis of Crohn disease, including the proinflammatory cytokine interleukin (IL)–23 that promotes a T-helper 17 response. Ustekinumab, approved by the U.S. Food and Drug Administration (FDA) for moderate-severe Crohn disease, is a humanized monoclonal anti–IL-12 and –IL-23 that targets p40 (the shared subunit of IL-12 and IL-23). Risankizumab is a humanized monoclonal antibody targeting the unique p19 subunit of IL-23. Inhibition of IL-23 by risankizumab is highly selective and may be superior to anti-p40 drugs for treating other immune-mediated diseases, such as plaque psoriasis.
In treatment-experienced patients with moderately to severely active Crohn disease, risankizumab induced and maintained clinical remission at 12 weeks vs. placebo. The ADVANCE and MOTIVATE trials confirmed efficacy, with 40% to 45% clinical remission with active therapy vs. 20% to 25% with placebo. Risankizumab appeared to be well tolerated, with few adverse events during 140 days of follow-up after induction therapy. A 52-week maintenance trial confirmed long-term safety and efficacy, with 52% to 55% sustained remission with risankizumab vs. 41% for placebo.
The role of risankizumab in relation to other biologic therapies is limited by the broad RCT exclusion criteria: perianal abscess, symptomatic strictures, fulminant colitis, or other complications. Trials including patients with these complications will be required to compare the efficacy and safety of IL-23–specific inhibition with IL-12 and IL-23 inhibition, and to monitor for long-term or rare treatment complications. Identifying nonresponders and what drives loss of response over time will also be of interest. The FDA has now approved risankizumab for adults with moderate-severe Crohn disease.