P0608Intestinal Ultrasound Assessment of Small Bowel Crohn’s Disease Following Risankizumab Initiation: Interim Analysis of PROGRESS

Abstract Background Intestinal ultrasound (IUS) is a valuable tool for evaluating treatment response to Crohn’s disease (CD) therapy. Achieving transmural remission (TR) on IUS is predictive of improved long-term outcomes. Bowel wall thickness (BWT) and colour doppler signal (CDS) are key parameters for assessing IUS response. Currently, the rate of IUS response and TR in ileal CD patients with strictures is unclear. Definitive strictures on IUS are defined as BWT 3mm, luminal narrowing, and pre-stenotic dilation (PSD), while probable strictures have fixed luminal narrowing without PSD. This study aims to elucidate the time and proportion of small bowel CD patients with and without strictures who achieve IUS response and/or TR following risankizumab (RIS) initiation. We report interim week (W) 48 results of PROGRESS, a prospective, observational cohort study of small bowel CD patients with and without strictures treated with RIS. Methods CD patients with TI involvement (BWT 3.0mm) with and without strictures initiating RIS were recruited and assessed by IUS at baseline, W12, 24, 36 and 48. IUS response is defined as decreased BWT of 25%, 2.0mm, or 1.0mm and one CDS reduction. TR is defined as normalization of all parameters (BWT 3mm, CDS (modified Limberg grade 0), stratification, inflammatory fat). Harvey Bradshaw Index (HBI), C-reactive protein (CRP), fecal calprotectin (fcal) was measured at each time point. Patient demographics, CD medication and surgical history was collected. Frequency of IUS response and TR was assessed. Mixed-effects analysis with Dunnett’s post-hoc test was utilized to compare between groups at baseline to W12, 24, 36, and 48. Results Of 66 patients recruited with ileal or ileocolonic CD, 45.5% (30/66) had strictures with median CD duration 11 years (IQR 4.9-24.6). Follow up was available for 95.5% (63) at W12, 77.3% (51) W24, 63.6% (42) W36, and 59.0% (39) W48. Prior to starting RIS, 72.7% (48) had prior advanced therapies (AT); 16.7% (11) trialed 3 AT, 22.7% (15) trialed 2 AT, and 33.3% (22) trialed 1 AT. Baseline BWT significantly improved by W36 (p = 0.03) and W48 (p = 0.002) following RIS. At W48, normalization of HBI, fcal, and/or CRP occurred in 75% (9/12) patients starting with HBI 5, 62% (8/13) with fcal 250 ug/g, and 100% (6/6) with CRP 8mg/L at baseline. IUS response was achieved in 33.3% (13/39) and TR in 12.8% (5/39) in small bowel CD with and without strictures at W48, respectively (Figure 1). Conclusion This prospective study is among the few that have evaluated IUS response and TR to RIS in ileal CD with and without strictures in an AT refractory population with 73% AT exposed. Future studies are needed to evaluate IUS response and remission on long-term outcomes in CD. Conflict of interest: Siddique, Mujtaba: No conflict of interest Rosentreter, Ryan: No conflict of interest O’brien, Maureen: I have nothing to disclose. Hoque, Sami: No conflict of interest Mak, Eva: No conflict of interest Shen, Hua: No conflict of interest Besney, Jonathan: No conflict of interest Chan, Melissa: No conflict of interest Devlin, Shane: No conflict of interest Ingram, Richard James Michael: Consultancy fees: AbbVie, Amgen, CellTrion, Eli Lilly, J & J Innovative Medicine, Pfizer, Sanofi, Takeda Pharmaceuticals. Speakers’ honoraria: AbbVie, Amgen, BioJAMP, Eli Lilly, Pfizer, Takeda Pharmaceuticals. Stocks: AbbVie, Eli Lilly, Merck (discretionary managed). Kaplan, Gilaad: Grant: Dr. Kaplan received grants for research from Ferring and for educational activities from AbbVie, Bristol Myers Squibb, Ferring, Fresenius-Kabi, Janssen, Pfizer, Takeda. Personal Fees: Dr. Kaplan has received honoraria for speaking or consultancy from AbbVie, Amgen, Janssen, Pfizer, and Takeda. Ma, Christopher: Consulting fees: AbbVie, Alimentiv, Amgen, Anaptys Bio, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Domain Therapeutics, Eupraxia, Eli Lilly, Ferring, Forte Biosciences, Fresenius Kabi, Gilead, Janssen, McKesson, Merck, Mirador Therapeutics, Pendopharm, Pfizer, Roche, Sanofi, Takeda, Tillotts Pharma Speaker’s fees: AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Merck, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma Royalties: Springer Publishing Research Support: AbbVie, Eli Lilly, Ferring, Pfizer Reji, Rohita: None Seow, Cynthia: CH. S reports advisory boards for Janssen, Abbvie, Takeda, Lilly, Ferring, Shire, Pfizer, Sandoz, Pharmascience, Fresenius Kabi, Amgen, Bristol Myers Squibb, and Celltrion and speaker for Janssen, Abbvie, Takeda, Lilly Ferring, Shire, Pfizer, Pharmascience, and Fresenius Kabi. Shukla, Tushar: No conflict of interest St-Pierre, Joelle: Consultant for Pfizer, Abbvie, Eli Lilly and Pendopharm, and speaker for Takeda. Novak, Kerri L.: Research Grants: Helmsley Trust, Pfizer, Janssen Adboard, consulting fees: Abbvie, Janssen, Pfizer, Pendopharm, Takeda, Elli Lilly, Celltrion, Bristal Myers Non financial support (ultrasound machine) McKesson Pharmcy. Pfizer, Celltrion Panaccione, Remo: Grant: Abbvie, Janssen, Pfizer, Takeda Other: Consultant for: Abbott, AbbVie, Abbivax, Alimentiv (formerly Robarts), Amgen, AnaptysBio, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JBio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Spyre Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Union Biopharma, Viatris, Ventyx, UCB Speaker’s Fees for: AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, Takeda Pharmaceuticals Advisory Boards for: AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JBio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, SandozShire, Sublimity Therapeutics, Takeda Pharmaceuticals, Ventyx. Dr. Lu, Cathy: Advisory board/consulting fees - Abbvie, Johnson and Johnson, Takeda, Ferring, Pendopharm, Merck, Celltrion, Pfizer, Lilly, Agomab. Research support - Abbvie, Helmsley Charitable Trust, Alberta Innovates.