Abstract Background Many patients (pts) with Crohn’s disease (CD) lose treatment response over time, underscoring the importance of treatments with sustained efficacy. Risankizumab (RZB) has previously shown durable clinical and endoscopic efficacy in pts with moderate-to-severe CD. 1, 2 Here, we continued to assess the durability of RZB efficacy in pts with moderate-to-severe CD and prior anti-TNF failure through 3 years of treatment in the ongoing SEQUENCE study. Methods In SEQUENCE (NCT04524611), pts randomised to RZB in Part 1 (the 48-week wk head-to-head study versus ustekinumab) who completed the wk 48 visit could receive open label maintenance RZB 360 mg SC every 8 wks during Part 2 starting at wk 52. 3, 4 In this post hoc analysis, durability of efficacy was defined as the proportion of pts among those who achieved clinical remission per CD activity index (CDAI) or per stool frequency/abdominal pain score (SF/APS) at wks 8 or 48, or endoscopic response, endoscopic remission, or mucosal healing at wks 24 or 48, that subsequently achieved the respective endpoint at later assessed timepoints. Pts with inadequate response to treatment could receive RZB rescue therapy. Details of RZB rescue therapy and endpoint definitions are provided in the Figure footnotes. Clinical assessments were performed post-baseline at wk 8, wk 24, and every 24 wks thereafter. Endoscopic assessments were performed post-baseline at wks 24, 48 and 148. Data included all intent-to-treat pts who received at least one dose of RZB in Part 2 and were summarised as observed (AO) and using modified nonresponder imputation (mNRI). Safety has been reported previously. 4 Results A total of 224 pts entered Part 2 and, per AO data, most pts who achieved clinical remission at wk 8 maintained clinical remission throughout later timepoints (Figure 1) ; clinical remission at wk 148 was achieved by 98. 5% (CDAI) and 88. 1% (SF/APS) of wk 8 clinical remitters. Durability of clinical remission was also observed throughout later timepoints in pts who achieved clinical remission at wk 48. Of pts who achieved endoscopic response, endoscopic remission, or mucosal healing at wk 24, 84. 7%, 78. 2%, and 67. 3% of pts, respectively, maintained the corresponding endpoint at wk 148; similar results at wk 148 were observed for pts who achieved these endoscopic endpoints at wk 48 (Figure 2). Data analysed using mNRI showed similar results to AO data. Conclusion Pts with moderate-to-severe CD and prior anti-TNF failure, a population generally considered to be more refractory, demonstrated durable clinical remission, endoscopic response, endoscopic remission, and mucosal healing through 148 wks of RZB treatment in the SEQUENCE study. References: 1. Ferrante M, et al. J Crohns Colitis. 2025;19 (Supplement₁): i113-i115. 2. Atreya R, et al. United Eur Gastroenterol J. 2025;12 (S8): 578. 3. Peyrin-Biroulet L, et al. N Engl J Med. 2024;391 (3): 213-223. 4. Peyrin-Biroulet L, et al. J Crohns Colitis. 2025;19 (Supplement₁): i1405-i1407. Conflict of interest: 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. 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, Ferrante, Marc: Research grants from AbbVie, EG Pharma, Celltrion, Janssen, Pfizer, Takeda and Viatris Consultancy fees from AbbVie, AgomAb Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, MRM Health, Merck Sharp and Dohme, Pfizer, Takeda and ThermoFisher Speakers’ fees from AbbVie, Biogen, Boehringer Ingelheim, Dr Falk Pharma, Ferring, Janssen-Cilag, Merck Sharp and Dohme, Pfizer, Takeda, Truvion Healthcare and Viatris Siegmund, Britta: Consulting fees from AbbVie, Abivax, Boehringer Ingelheim, BMS, Dr Falk, Endpoint Health, Galapagos, Gilead, Janssen, Landos, Lilly, Pfizer, and Takeda, and speaker’s fees from AbbVie, AlfaSigma, BMS, CED Service, Dr Falk, Ferring, Galapagos, Janssen, Lilly, MSD, Pfizer, and Takeda. Cao, Qian: has served as a steering committee adviser for Bristol Myers Squibb Company, and Janssen Research Development, LLC and has received research grants from Takeda and Johnson & Johnson. Van Haaren, Stijn: Full-time employee of AbbVie and may own AbbVie stock or stock options. Crowley, Jameson: Full-time employee of AbbVie and may own AbbVie stock or stock options Anschutz, Toni: Full-time employee of AbbVie and may own AbbVie stock or stock options. Garrison, Andrew: Contractor of AbbVie and may own AbbVie stock or stock options. Huang, Xiu: Full-time employee of AbbVie and may own AbbVie stock or stock options. Dubinsky, Marla C: Received consulting and advisory fees from AbbVie, Abivax, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Genentech, Gilead, GSK, Janssen, Johnson and Johnson, Merck, Pfizer, Prometheus Labs, Prometheus Biosciences, Sanofi, Spyre and Takeda.
Atreya et al. (Thu,) studied this question.