INSPIRE: Risankizumab meets all efficacy endpoints in UC

Risankizumab induction therapy was superior to placebo in achieving clinical remission in participants with moderately to severely active ulcerative colitis (UC), according to the primary findings of the phase 3 INSPIRE study. The therapy was well tolerated, and the observed safety profile was similar to previous reports on this agent.

The IL-23 inhibitor risankizumab was tested in participants with moderately to severely active UC with an inadequate response or intolerance to conventional and/or advanced therapies in a double-blind, placebo-controlled, phase 3 trial called INSPIRE (NCT03398148) [1]. Participants received 1,200 mg of risankizumab intravenously every 4 weeks (n=650) or a placebo (n=325). At baseline, about 35% of the participants were on corticosteroids, 73% were on aminosalicylates, and 16.5% were on immunosuppressants. Also, over 50% of the participants had an inadequate response or were intolerant to advanced therapies. The primary endpoint was the clinical remission rate at week 12, per adapted Mayo score, defined as stool frequency subscore ≤1 and not greater than baseline, rectal bleeding subscore of 0, and endoscopic subscore ≤1 without friability. Prof. Edouard Louis (Liège University Hospital, Belgium) presented the key results.

The primary endpoint was met by 20.3% of the participants in the risankizumab arm and by 6.2% of those in the placebo arm (P<0.0001). The corresponding clinical remission rates in the advanced therapies-naïve population were 29.7% and 8.4%. In those with an inadequate response or intolerance to advanced therapies, the clinical remission rates were 11.4% and 4.3%, respectively. Furthermore, the clinical response rate per adapted Mayo score at week 12 was 64.3% in the risankizumab arm and 35.7% in the placebo arm (P<0.0001). Notably, the clinical response rates already favoured risankizumab over placebo at week 4 (52.2% vs 30.5%; P<0.0001). Prof. Louis added that endoscopic, histologic, and patient-reported endpoints significantly favoured risankizumab over placebo.

Adverse events (AEs) were reported in 49.7% of the participants on placebo and 42.1% of those on risankizumab. Finally, the rate of serious AEs appeared to be higher in the placebo arm, at 10.2%, compared with 2.3% in the active arm. Worsening of UC (10.2%), anaemia (6.5%), and COVID-19 (5.9%) were the most common AEs in the placebo arm. In the risankizumab arm, the corresponding rates for these AEs were 1.7%, 3.4%, and 4.8%. Finally, hepatic events occurred numerically more frequently in the placebo arm than in the risankizumab arm (4.3% vs 1.5%).

Induction therapy with risankizumab showed benefits over placebo in clinical, endoscopic, histologic, and patient-reported outcomes in participants with UC, and was well-tolerated in this population.

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   1. Louis E, et al. Risankizumab induction therapy in patients with moderately to severely active ulcerative colitis: efficacy and safety in the randomised phase 3 INSPIRE study. OP21, UEG Week 2023, 14–17 October, Copenhagen, Denmark.

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Posted on 7 December, 20238 April, 2024