Risankizumab, an interleukin (IL)-23 p19 inhibitor, has shown promising results as an induction therapy for patients with moderately to severely active Crohn's disease. The findings come from two Phase 3 randomized, double-masked, placebo-controlled studies, ADVANCE and MOTIVATE, and were recently published.
The studies evaluated the safety and efficacy of risankizumab in patients aged 16-80 years who had previously shown intolerance or inadequate response to one or more approved biologics or conventional therapy (ADVANCE) or to biologics (MOTIVATE). Participants were randomly assigned to receive intravenous risankizumab (600 mg or 1200 mg) or placebo at weeks 0, 4, and 8.
Key Findings from ADVANCE and MOTIVATE
Both trials met all co-primary endpoints at week 12 with both doses of risankizumab (p ≤ 0.0001). The co-primary endpoints were clinical remission, defined by Crohn's Disease Activity Index (CDAI) or patient-reported outcome criteria (average daily stool frequency and abdominal pain score), and endoscopic response.
In the ADVANCE trial, the CDAI clinical remission rate was 45% with risankizumab 600 mg and 42% with risankizumab 1200 mg, compared to 25% with placebo. The stool frequency and abdominal pain score clinical remission rate was 43% with risankizumab 600 mg and 41% with risankizumab 1200 mg, versus 22% with placebo. The endoscopic response rate was 40% with risankizumab 600 mg and 32% with risankizumab 1200 mg, compared to 12% with placebo.
Similar results were observed in the MOTIVATE trial. The CDAI clinical remission rate was 42% with risankizumab 600 mg and 40% with risankizumab 1200 mg, versus 20% with placebo. The stool frequency and abdominal pain score clinical remission rate was 35% with risankizumab 600 mg and 40% with risankizumab 1200 mg, compared to 19% with placebo. The endoscopic response rate was 29% with risankizumab 600 mg and 34% with risankizumab 1200 mg, versus 11% with placebo.
Safety and Tolerability
The overall incidence of treatment-emergent adverse events was similar among the treatment groups in both trials. Three deaths occurred during induction (two in the placebo group [ADVANCE] and one in the risankizumab 1200 mg group [MOTIVATE]). The death in the risankizumab-treated patient was deemed unrelated to the study drug.
Implications for Crohn's Disease Treatment
These findings suggest that risankizumab is an effective and well-tolerated induction therapy for patients with moderately to severely active Crohn's disease. The study authors concluded that risankizumab represents a valuable new option for managing this challenging condition. The results offer hope for patients who have not responded well to existing treatments.
