DOP76 Individual and comprehensive symptom resolution after induction and maintenance therapy with risankizumab in patients with moderately to severely active Ulcerative Colitis: A post-hoc analysis of INSPIRE and COMMAND studies
Authors: Tinoco da Silva Torres J , Panés J , Siegel C A , Dubinsky M C , Dulai P S , Tanida S , Danese S , Levine P , Lai J H , Sharma D , Shukla N , Remple V , Hecht P M , Sanchez Gonzalez Y , Panaccione R 
Published: January 2024

Abstract

Background
Short-term treatment goals in ulcerative colitis (UC) are to control inflammation and reduce symptoms, while long-term goals include endoscopic healing, absence of disability and normalisation of quality of life. This post-hoc analysis examined the effect of induction and maintenance treatment with risankizumab (RZB) on UC-related symptoms of abdominal pain (AP), bowel urgency (BU), tenesmus (TN), faecal incontinence (FI), nocturnal bowel movements (NBM), and sleep interruption (SI).

Methods
Patients (pts) from the INSPIRE induction (NCT03398148) study received intravenous (IV) RZB 1200 mg or placebo (PBO) induction treatment at weeks (wks) 0, 4, and 8. Pts with a clinical response to RZB IV treatment were randomised 1:1:1 in the COMMAND maintenance (NCT03398135) study to subcutaneous (SC) RZB 180 or 360 mg, or PBO (RZB withdrawal). Each individual symptom was assessed (AP, BU, TN, FI, NBM, and SI), as well as comprehensive symptom resolution (defined as complete resolution of all 6 UC-related symptoms). Outcomes were measured at induction wks 0, 4, 8 and 12 and maintenance wks 0 and 52. Results were reported as adjusted percentage differences of resolution for each individual symptom and for comprehensive symptom resolution of RZB vs PBO and analysed based on corresponding 95% confidence intervals and p-values.

Results
A total of 975 pts (PBO IV n=325; RZB IV n=650;) were enrolled in induction and 548 (PBO [withdrawal] SC n=183; RZB 180 mg SC n=179; RZB 360 mg SC n=186) in the maintenance study. As early as wk 4 of induction, greater proportions of RZB- vs PBO-treated pts were experiencing resolution of each individual symptom (p≤0.01). These benefits persisted through the end of induction with the greatest improvements observed in NBM and SI (both p&lt;0.001; Table). Among induction responders, differences between RZB 180 mg SC and PBO (withdrawal) SC were sustained for all symptoms through wk 52 of maintenance (p≤0.05); results were similar between RZB 360 mg vs PBO (withdrawal) SC, except for AP. A greater proportion of pts treated with RZB (21.8%) vs PBO (withdrawal) SC (9.5%) achieved complete symptom resolution by end of induction (p≤0.001) and maintenance (23.5% RZB 180 mg SC vs 14.2% PBO [withdrawal] SC p≤0.05).

Conclusion
In this post-hoc analysis, RZB showed individual and comprehensive improvement across a range of important UC symptoms at the end of induction, compared with PBO. Improvements in UC-related symptoms were observed as early as wk 4 of induction treatment and were sustained with maintenance treatment through wk 52. These benefits demonstrate the potential of RZB to achieve both short- and long-term treatment goals based on comprehensive symptom resolution.