Analysis of long-Term safety and efficacy of risankizumab in patients with moderate-To-severe crohn's disease: 3-year results from the sequence study

Abstract

Background: Part 2 of the ongoing SEQUENCE study examines the long-Term efficacy and safety of risankizumab (RZB), an interleukin-23 p19 inhibitor, in patients (pts) with moderate-To-severe Crohn's disease (CD). Here, we report the 3-year (yr) results from the SEQUENCE study (2-yr results from Part 2). Method(s): In Part 2 of SEQUENCE (NCT04524611), pts randomised to RZB who completed the Part 1 week (wk) 48 visit continued on open-label 360mg subcutaneous (SC) RZB every 8 wks (Q8w).1 Clinical remission (per CD activity index CDAI] and per stool frequency SF]/abdominal pain score APS]), steroid-free clinical remission, endoscopic response, endoscopic remission, steroid-free endoscopic remission, deep remission, mucosal healing, Inflammatory Bowel Disease Questionnaire (IBDQ) remission, and normalisation of high-sensitivity C-reactive protein (hs-CRP) and faecal calprotectin (FCP) levels were assessed through wk 148 (endpoints defined in Figure footnote). Inadequate responders could receive =16 weeks apart.1 All intent-To-Treat (ITT) pts were assessed as observed (AO) and using modified nonresponder imputation (mNRI; multiple imputation for missed assessments, including RZB discontinuation for reasons other than "lack of efficacy/adverse event limited only to CD"). Data before receiving rescue treatment are presented (see Figure footnote). Treatment emergent adverse events (TEAEs) reported on or after the first RZB dose in Part 2 were analysed (cutoff date: 02JUL2025). Result(s): In total, 224 ITT pts entered Part 2. Compared to wk 52, data AO showed similar or higher rates of clinical remission at wk 148 (CDAI: 76.4% vs 86.3%; SF/APS: 72.1% vs 75.9%), steroid-free clinical remission (CDAI: 75.9% vs 83.5%; SF/APS: 72.1% vs 73.0%), IBDQ remission (62.1% vs 69.0%), endoscopic response (55.8% vs 65.1%), endoscopic remission (39.2% vs 48.8%), steroid-free endoscopic remission (38.7% vs 48.3%), mucosal healing (37.3% vs 43.6%), and deep remission (31.5% vs 36.8%) (Figure). Also, compared to wk 52, a greater proportion of pts with elevated biomarker levels at baseline had normalised levels at wk 148 (hs-CRP: 53.1% vs 69.4%; FCP: 56.9% vs 66.3%). Lower efficacy rates were observed per mNRI but also showed sustained efficacy through wk 148. The profiles of TEAEs and TEAEs of special interest were consistent with the known safety profile of RZB (Table).2,3 No deaths occurred during Part 2. Conclusion(s): Three yrs of continuous RZB therapy in SEQUENCE resulted in durable long-Term clinical, endoscopic, and quality of life benefits. The safety profile is consistent with the known safety profile of RZB and supports long-Term RZB treatment.