Risankizumab more efficacious in colonic than in ileal Crohn’s disease

A post-hoc analysis of the phase 3 ADVANCE, MOTIVATE, and FORTIFY trials assessing risankizumab in participants with Crohn’s disease (CD) confirmed the efficacy of induction and maintenance therapies with this agent. The analysis further showed that risankizumab therapy is more efficacious in participants with CD who had colonic involvement than in those who had ileal involvement.

Risankizumab is an IL-23 inhibitor under investigation for the treatment of patients with CD.

Although several phase 3 trials have demonstrated the safety and efficacy of risankizumab as intravenous induction therapy and subcutaneous maintenance therapy in patients with CD, the efficacy of this therapy regarding disease location has not yet been investigated. “And we know that disease location may affect treatment outcomes of biologic therapies in CD,” explained Dr Peter Bossuyt (Imelda General Hospital, Belgium) [1,2]. Therefore, the current, post-hoc analysis used the data of the phase 3 ADVANCE (NCT03105128), MOTIVATE (NCT03104413), and FORTIFY (NCT03105102) trials to analyse the efficacy of risankizumab according to disease location [2].

Clinical remission^a at week 12 was higher in participants with colonic involvement (54.3%; n=190; P<0.001) and participants with ileal-colonic involvement (39.7%; n=252; P<0.001) who received risankizumab induction therapy compared with participants who received placebo (23.8% and 20.7%, respectively). In participants with ileal disease (n=85), a benefit  of risankizumab was seen over placebo (33.7% vs 22.2%), although not significant. Similar results were reported for endoscopic responses^b and endoscopic remission^c at week 12.

Furthermore, risankizumab maintenance therapy significantly outperformed placebo in participants with colonic (54.0% [n=59] vs 37.1% [n=62]; P<0.05) or ileal-colonic involvement (53.3% [n= 67] vs 40.5% [n=79]; P<0.05), but not ileal disease (40% [n=15] vs 52.2% [n=23]), with regard to clinical remission at week 52. Dr Bossuyt added that endoscopic response, a more objective endpoint, did show benefits of risankizumab compared with placebo in participants with ileal disease (26.7% [n=15] vs 8.7% [n=23]). The number of participants with ileal disease in the maintenance analysis was low (n=38), thus these results should be interpreted with caution.

“This study confirms the efficacy of risankizumab in patients with moderately to severely active CD and confirms greater improvements in patients with colonic involvement,” said Dr Bossuyt. “Unfortunately, the treatment success is lower in participants with ileal disease, a pattern we have seen for other molecules as well. I believe that these results show us that we must recognise ileal and colonic Crohn’s disease as 2 separate conditions, extending beyond the difference in disease location.”

a. Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) >150.

b. Endoscopic response is defined as a >50% decrease from baseline in SES-CD, or a 2-point reduction from baseline for patients with ileal disease and baseline SES-CD of 4.

c. Endoscopic remission was defined as a SES-CD ≤4 and at least a 2-point reduction vs baseline with no subscore greater than 1 in any individual variable.

1. Rivière P, et al. Am J Gastroenterol. 2021;116(1):134–141.
2. Bossuyt P, et al. Efficacy of risankizumab induction and maintenance therapy by baseline Crohn’s Disease location: Post hoc analysis of the phase 3 ADVANCE, MOTIVATE, and FORTIFY studies. OP40, ECCO 2022, 16–19 February.

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Posted on 12 April 20228 April 2024