Real-world effectiveness of risankizumab in Crohn's Disease: The UK Experience

Abstract

Background Risankizumab is an IL-23 inhibitor which received approval for Crohn’s disease (CD) by the NICE committee in May 2023. Our aim was to evaluate the real-world outcomes of risankizumab in the United Kingdom (UK). Methods We conducted a retrospective, multicentre, cohort study across twenty health boards in the UK, of patients with CD treated with risankizumab between the 1st of January, 2021 and the 1st of November 2024. Our primary outcome was treatment persistence at 6 months. Our secondary endpoints were treatment persistence, steroid-free clinical remission (Harvey-Bradshaw index <5), biomarker remission (CRP =5 mg/L and FCAL <250 µg/g), at 3, 6 and 12 months, and if effectiveness was different between ustekinumab naive and exposed patients. Patients who discontinued therapy for any reason were considered treatment-failure for all indices after the time point they ceased therapy. We recorded adverse events, including hospitalisation, bowel resection, infection, and death. Results We identified 558 patients who commenced risankizumab, of which 526 patients had 3 month outcome data available with a median follow-up time of 28 weeks (IQR, 19-41 weeks). The median number of advanced therapy exposures were 3 (2-4), with 90% (475/526) having failed anti-TNF therapy, and 73% (382/526) having failed ustekinumab (Table 1). Treatment persistence was 97.5%, 94.8% and 89.5% at 3, 6 and 12 months (Figure 1). Unadjusted persistence rates for ustekinumab naïve vs ustekinumab exposed patients were 93.8% vs 95.3% and 93.8 % vs 89.3% at 6 and 12 months respectively (p=0.7). Rates of clinical remission were 59% (211/358), 50% (77/154), and 44% (14/32) at 3, 6 and 12 months. Rates of clinical remission for ustekinumab naive vs exposed were 67% (70/104) vs 55% (141/253) and 60% (21/35) vs 47% (56/119) at 3 and 6 months respectively. CRP remission rates were 57% (266/465), 52% (108/208), and 53% (28/53) at 3, 6 and 12 months. FCAL remission rates were 58% (140/243), 48% (55/114), and 44% (17/38) at 3, 6 and 12 months. There was a significant reduction in median HBI, CRP and FCAL during follow-up (Figure 1). We observed that 12% (62) of patients were hospitalised due to symptomatic CD (58) or an implicated adverse event (4). We observed that 3% (17/526) underwent CD related resectional surgery. Adverse events occurred in 16% (85/526) of the cohort. Serious adverse events occurred in 5% (28/526), of which 25 were hospitalisations. Conclusion Risankizumab was effective in a large, real-world, medically refractory CD cohort with excellent short-term persistence and good clinical and biochemical remission rates. Persistence rates were similar between ustekinumab naive and exposed patients, however clinical remission rates were higher in the naive group.