Real-World Risankizumab Outcomes in Refractory CD : Frontline Gastroenterol | May 2026

Introduction

Risankizumab is a selective interleukin-23 p19 inhibitor approved for moderate-to-severe Crohn’s Disease following strong efficacy signals in phase III trials. However, real-world evidence in heavily pretreated Crohn’s disease populations, particularly after prior biologic and ustekinumab exposure, remains limited. This large multicentre UK cohort evaluated the effectiveness, persistence and safety of risankizumab across routine clinical practice.

Problem Statement

Many patients with Crohn’s disease experience failure of multiple advanced therapies, including anti-TNF agents and ustekinumab, creating substantial therapeutic challenges. Whether selective IL-23 p19 inhibition remains effective after prior IL-12/23 blockade in real-world refractory populations has remained uncertain.

Summary

This retrospective multicentre study included 763 patients treated across 25 UK health boards, representing one of the largest real-world risankizumab cohorts reported to date. The population was highly treatment refractory, with 92% previously exposed to anti-TNF therapy, 72% previously treated with ustekinumab and a median of three prior advanced therapy exposures. More than half had prior luminal surgery and 16% had a stoma at treatment initiation, underscoring the severe disease burden of the cohort.

Despite this complexity, risankizumab demonstrated remarkably high treatment persistence, reaching 97.8% at 3 months, 95.4% at 6 months and 89.2% at 12 months. Persistence remained robust even among patients previously exposed to ustekinumab, suggesting that selective IL-23 p19 inhibition may retain efficacy despite prior IL-12/23 blockade. Prednisolone use at treatment initiation was the only significant predictor of reduced persistence, likely reflecting higher inflammatory burden and more refractory disease.

Clinical and biochemical outcomes were similarly encouraging. Steroid-free clinical remission occurred in 59% at 3 months, 52% at 6 months and 50% at 12 months. CRP remission rates exceeded 50% throughout follow-up, while faecal calprotectin remission rates reached 44% at both 6 and 12 months. Significant improvements in Harvey-Bradshaw Index, inflammatory biomarkers, abdominal pain and stool frequency were observed across treatment intervals. Importantly, remission rates were largely comparable between ustekinumab-naïve and ustekinumab-exposed patients, supporting the mechanistic distinction between IL-23 p19 blockade and p40 inhibition.

The study additionally provided important real-world insights into perianal disease. Among patients with active perianal Crohn’s disease, approximately one-third achieved clinical perianal response by 12 weeks, while most avoided new perianal complications during follow-up. These findings support a potential role for risankizumab in fistulising disease, although dedicated prospective studies remain necessary.

Safety outcomes were favourable overall. Adverse events occurred in 17% of patients, though many reflected disease-related hospitalisations rather than drug toxicity. Serious infections requiring hospitalisation were infrequent, and discontinuation due to adverse effects remained uncommon. The overall safety profile aligned closely with phase III trial experience and previously published smaller real-world cohorts.

Overall, this large UK real-world analysis confirms that risankizumab is highly effective and durable in medically refractory Crohn’s disease, including patients with multiple prior biologic failures and previous ustekinumab exposure. The findings reinforce IL-23 p19 inhibition as an important therapeutic mechanism in advanced Crohn’s disease and support its expanding integration into complex IBD treatment algorithms.