Risankizumab in Crohn's disease

Risankizumab is a fully human immunoglobulin G monoclonal antibody that binds with high affinity to the p19 subunit of IL-23 (1)

ADVANCE and MOTIVATE

• ADVANCE and MOTIVATE were randomised, double-masked, placebo-controlled, phase 3 induction studies (2)
• eligible patients aged 16-80 years with moderately to severely active Crohn's disease, previously showing intolerance or inadequate response to one or more approved biologics or conventional therapy (ADVANCE) or to biologics (MOTIVATE), were randomly assigned to receive a single dose of intravenous risankizumab (600 mg or 1200 mg) or placebo (2:2:1 in ADVANCE, 1:1:1 in MOTIVATE) at weeks 0, 4, and 8
• both RCTs reported improved clinical remission rates with intravenous risankizumab in patients with moderately to severely active Crohn's disease (Advance; n=931; 45% with 600 mg; 42% with 1200 mg vs 25% with placebo: Motivate; n=618; 42%, 40% vs 20%, respectively)
• study authors concluded:
  • risankizumab was effective and well tolerated as induction therapy in patients with moderately to severely active Crohn's disease

FORTIFY

• at week 52, the Fortify RCT reported greater clinical remission and endoscopic response rates with subcutaneous risankizumab 360mg vs placebo (n=542; 52% vs 41%) and with subcutaneous risankizumab 180 mg vs withdrawal (55% vs 47%) (3)
  • showed that subcutaneous risankizumab is a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active Crohn's disease and offers a new therapeutic option for a broad range of patients by meeting endpoints that might change the future course of disease

The three RCTs (Advance, Motivate and Fortify) demonstrate the therapeutic effect of IL-23-specific inhibition in patients with Crohn's disease, and include the co-primary endpoints of clinical remission and endoscopic response

Reference:

• Ferrante M, Feagan BG, Panés J, et al. Long-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn's Disease: Results from the Phase 2 Open-Label Extension Study. J Crohns Colitis. 2021;15(12):2001-2010. doi:10.1093/ecco-jcc/jjab093
• D'Haens PG et al. Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. Lancet May 28th 2022.
• Ferrante P et al. Risankizumab as maintenance therapy for moderately to severely active Crohn's disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Lancet May 28th 2022.