DOP031Analysis 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). Methods 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 ≤2 rescue treatments (600 mg RZB intravenous dose followed by 360 mg SC Q8W), ≥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). Results 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 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. References: 1. Peyrin-Biroulet L, et al. N Engl J Med. 2024;391 (3): 213-223. 2. Papp KA, et al. Dermatol Ther. 2021;11 (2): 487-497. 3. Ferrante M, et al. J Crohns Colitis. 2024;18 (Supplement₁): i168-i170. Conflict of interest: Peyrin-Biroulet, Laurent: CONSULTING: AbbVie, Abivax, Adacyte, Alimentiv, Alfasigma, Amgen, Apini, Banook, BMS, Celltrion, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, LifeMine, Medac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Par’ Immune, Pfizer, Prometheus, Roche, Roivant, Samsung, Sandoz, Sanofi, Sorriso, Spyre, Takeda, Teva, ThirtyfiveBio, Tillots, Vectivbio, Vedanta, Ventyx. LECTURE: AbbVie, Alfasigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots Atreya, Raja: RA has served as a speaker, or consultant, or received research grants from AbbVie, Abivax, AlfaSigma, Arena Pharmaceuticals, Astra-Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion Healthcare, Dr Falk Pharma, Galapagos, Gilead, GlaxoSmithKline, InDex Pharmaceuticals, Johnson & Johnson, Lilly, Materia Prima, Merck Sharpe & Dohme, Pfizer, Roche Pharma, Takeda Pharma, Viatris. Danese, Silvio: Personal Fees: AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc. , Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc. , Vial, Vifor Lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc. , Gilead, Janssen, Mylan, Pfizer, Takeda Lindsay, James: Investigator Initiated Research Grant: Takeda, Abbvie, Gilead Personal Fees: I have received fees for speaking and may have received support to attend academic conferences from: Abbvie UK/Global, Bristol Myers Squib, Cornerstones US, Gilead, Galapagos, Lilly, MSD UK, Ferring UK, Ferring Intl. , Celltrion, Takeda, Pfizer, Janssen, Tillotts, Other: I serve of the advisory board of Abbvie UK/Global, Alpini, Astra Zeneca, Engytix, Galapagos, Gilead, GSK, Lily, MSD, Ferring UK, Ferring Intl. , Celltrion, Takeda, Pfizer, Janssen, Shattucks Laboratory, Chapman, J. Casey: Consultant of AbbVie and Medtronic Advisory Board of AbbVie, Pfizer, Takeda Speaker Bureau for AbbVie, Bristol Myers Squib, Janssen, Pfizer, Takeda. Anschutz, Toni: AbbVie employee and owns shares of AbbVie stock Huang, Xiu: Full-time employee of AbbVie and may own AbbVie stock or options. Zambrano, Javier: Full-time employee of AbbVie and may own AbbVie stock or options. Aponte, Fernando: Full-time employee of AbbVie and may own AbbVie stock or options. Joshi, Namita: Full-time employee of AbbVie and may own AbbVie stock or options. Cross, Raymond: Consultant and an advisory board participant for AbbVie, Bristol Myers Squibb, Janssen, Magellan Health, Option Care, Pharmacosmos, Pfizer, Samsung Bioepis, Sandoz, and Sebela has received speaker fees from AbbVie, Bristol Myers Squibb, Janssen, and Pfizer Member of the Executive Committee IBD Education Group Scientific Co-Director CorEvitas Registry Member Data Safety Monitor Board Gilead and has received investigator-led research grants from Janssen.