SEQUENCE: Risankizumab doubles endoscopic remission rates compared with ustekinumab in CD

Risankizumab outperformed ustekinumab in achieving endoscopic remission in participants with Crohn’s disease (CD). Moreover, risankizumab was superior to ustekinumab for all secondary efficacy endpoints. The safety profiles of the 2 agents were similar, albeit participants on ustekinumab had a numerically higher rate of serious adverse events (AEs).

The phase 3, head-to-head SEQUENCE trial (NCT04524611) compared the efficacy and safety of the specific IL-23 inhibitor risankizumab with the IL-12/IL-23 inhibitor ustekinumab in participants with moderate-to-severe CD who had failed at least 1 TNF inhibitor [1]. The participants (n=520) were randomised to 1 of these agents in a 1:1 ratio. The primary endpoints were Crohn’s disease activity index (CDAI) clinical remission at week 24, tested in 50% of the participants for non-inferiority, and endoscopic remission at week 48, assessed for superiority. Prof. Laurent Peyrin-Biroulet (University Hospital of Nancy, France) presented the main outcomes.

At week 24, CDAI clinical remission rates were 58.6% and 39.5% in the risankizumab and ustekinumab arms, respectively, meeting the non-inferiority endpoint (P<0.0001). Moreover, at week 48, the endoscopic remission rate was 31.8% in the risankizumab group and 16.2% in the ustekinumab group (P<0.0001). “All secondary endpoints significantly favoured risankizumab over ustekinumab,” mentioned Prof. Peyrin-Biroulet. The agents were similar concerning safety: 85.1% and 82.6% of the participants in the risankizumab arm and the ustekinumab arm, respectively, experienced treatment-emergent adverse events (AEs).“The serious AE rate was higher in the ustekinumab arm (17.4% vs 10.3%) due to a higher rate of CD flares,” added Prof. Peyrin-Biroulet. Of note, the 2 drugs also had similar rates of malignancies (14.4% in the risankizumab arm vs 11.9% in the ustekinumab arm) and serious infections (3.9% vs 5.2%, respectively).

In the SEQUENCE trial, risankizumab met both primary endpoints of non-inferiority for clinical remission at week 24 and superiority for endoscopic remission at week 48 versus ustekinumab with a comparable safety profile. Therefore, the benefit-risk assessment favours risankizumab over ustekinumab in participants with CD who had failed at least 1 TNF inhibitor.

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   1. Peyrin-Biroulet L, et al. Risankizumab versus ustekinumab for patients with moderate to severe Crohn’s disease: results from the phase 3b SEQUENCE study. LB01, UEG Week 2023, 14–17 October, Copenhagen, Denmark.

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Posted on 7 December 202317 May 2024