OP36 Risankizumab Versus Ustekinumab for the Achievement of Clinical Outcomes and Symptom Improvement in Patients With Moderate To Severe Crohn’s Disease: Results From the Phase 3b SEQUENCE Trial
Authors: Dubinsky M C , D’Haens G , Atreya R , Abraham B , Armuzzi A , Arguelles-Arias F , Lindsay J O , Patel K , Neimark E , Huang X , Anschutz T , van Haaren S , O’Brien D , Ferrante M 
Published: January 2024

Abstract

Background
The efficacy and safety of risankizumab (RZB) and ustekinumab (UST) in patients (pts) with moderate to severe Crohn's disease (CD) refractory to prior anti-tumour necrosis factor (TNF)α therapy were compared in the SEQUENCE head-to-head study. Previously, wk24 CD activity index (CDAI) clinical remission rates (CDAI&lt;150) were reported for 50% of pts (first primary endpoint);1 here, the efficacy of RZB versus (vs) UST for achieving wk24 clinical remission and other symptomatic improvements in the full pt population was assessed.

Methods
SEQUENCE (NCT04524611) was an open-label, multicenter, randomised, efficacy assessment-blinded study in pts with moderate to severe CD (defined in Figure footnote) refractory to TNFα therapy. Pts in the primary efficacy analysis set were randomised 1:1 to receive RZB (intravenous [IV] 600mg induction at BL, week (wk)4 and wk8, then 360mg subcutaneous [SC] maintenance every 8 wks [Q8w], starting at wk12) or UST (single weight-based IV induction followed by a 90mg Q8w SC maintenance starting at wk8) up to wk48. A mandatory steroid taper began at wk2. Randomisation was stratified by BL steroid use and number of failed anti-TNFs. Prespecified non-ranked endpoints included CDAI clinical response and stool frequency (SF)/abdominal pain score (APS) clinical remission (definitions in Figure footnote). CDAI clinical remission at wk48 was a ranked secondary endpoint. CDAI clinical remission at wks 8 and 24, and changes from BL in avg daily APS, SF, and CDAI, were evaluated post-hoc. Binary endpoints were analysed using non-responder imputation while incorporating multiple imputation to handle missing data due to COVID-19 and/or geopolitical conflict. Continuous endpoints were analysed using a mixed-effect model with repeated measures. All P values are nominal, except for wk48 CDAI clinical remission (ranked secondary endpoint).

Results
With RZB vs UST, respectively, greater rates of CDAI clinical remission (59.6% [152/255] vs 42.6% [113/265]; P=0.0001), SF/APS clinical remission (55.7% vs 41.1%; P&lt;0.001) and CDAI clinical response (69.8% vs 54.3%; P&lt;0.001) were observed at wk24; similar results were observed at wk48 (Figure). Mean BL APS in the RZB and UST groups was 1.9 (both groups), SF was 5.5 and 5.6, and CDAI was 309.4 and 310.1, respectively. Least square (LS) mean changes from BL in APS, SF, and CDAI were greater with RZB vs UST and observed early as wk8 (APS: -0.9 vs -0.8; SF: -3.0 vs -2.3; P&lt;0.001; CDAI: -136.3 vs -117.1; P&lt;0.05) (Figure). The safety profiles of RZB and UST were consistent with published results.1

Conclusion
In this head-to-head study, improvements in symptomatic outcomes in pts with CD were greater with RZB than UST over 48 wks of treatment.
1doi.org/10.1002/ueg2.12474