DOP007Ustekinumab for Fistulizing Perianal Crohn’s Disease: week-48 results from the USTAP Randomized Placebo-ControlledTrial

Abstract Background Fistulizing perianal Crohn’s disease (CD) remains a significant challenge, with few randomized controlled trials. The USTAP (NCT04496063) trial aimed to evaluate the efficacy and safety of ustekinumab (UST) in patients with active draining perianal fistulas in a multicenter randomized controlled design. Methods This double-blind, placebo-controlled, multicenter GETAID trial enrolled adult patients with active draining fistulizing perianal CD. Eligible patients were randomized 1:1, after seton placement when needed, to receive UST (6 mg/kg IV at baseline followed by 90 mg SC at week 8, then every 8 weeks) or placebo. The primary endpoint was combined clinical remission (absence of drainage from all external fistula openings) and radiological remission (absence of abscesses 2 cm confirmed by blinded central MRI) at week 12 (1). At week 12, placebo non-responders could switch to UST, and UST non-responders could be intensified during the open-label phase. Secondary endpoints included clinical remission, radiological remission, and safety. Endpoints at week 12 were independently reviewed by a blinded adjudication committee. Randomization was stratified by prior anti-TNF exposure and study center. The intended sample size was 73 patients per group to detect a 20% difference in remission rates (power 80%, alpha 5%). Due to slow recruitment, the study was discontinued in June 2024, without unblinding the study data. Results Thirty-two patients were andomized (UST: 16; placebo: 16) across 10 French centers. 70% had prior anti-TNF exposure. At baseline, 84% had 1 draining fistula, 16% had 2, and 25% had abscesses. At week 12, combined remission was achieved in 62% with UST vs 25% with placebo (Table). At week 12, clinical remission occurred in 69% vs 31%, and radiologic remission in 87.5% vs 75% (UST vs placebo, respectively). At week 48, treatment persistence from randomization was 56% (9/16) in the UST arm, and 12.5% (2/16) in the placebo arm. Nine placebo-patients switched to UST during the open-label phase. At week 48, combined remission was 7/16 (50%) in the « placebo-UST » arm vs 5/16 (31%) in the UST arm. Adverse events (AE) and serious adverse events (SAE) were similar between groups, and 14 SAEs were reported (11 in the placebo group and 3 in the UST group), leading to study discontinuation by week 6 in two placebo-treated patients (anal abcess and peri-ileal abscess). Conclusion In this trial, where the majority of patients had prior anti-TNF exposure, the observed short-term clinical benefit of UST supports its use in fistulizing perianal CD, with treatment persistence in half of UST-treated patients. References: (1)Panés J, et al; ADMIRE CD Study Group Collaborators. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn’s disease: a phase 3 randomised, double-blind controlled trial. Lancet. 2016 Sep 24;388(10051):1281-90. doi: 10.1016/S0140-6736(16)31203-X. Epub 2016 Jul 29. PMID: 27477896. Conflict of interest: Wils, Pauline: Johnson & johnson, Takeda, Amgen, Abbvie, Celltrion, Ferring Nancey, Stéphane: board membership and lecturing fees from Abbvie, Takeda, Celltrion Healthcare, Pfizer, Galapagos, Johnson & Jonshon, Lilly, Fresenius, Amgen, Medac, MSD. Messmer, Elodie: No conflict of interest Bourreille, Arnaud: Grant: Takeda, MaunaKea technologies Personal Fees: AbbVie, Celltrion, Ferring, Galapagos, Gilead, MSD, Medtronic, OSE Immunotherapeutics, Janssen, Pfizer, Roche, Takeda, Tillotts, Vifor pharma Buisson, Anthony: Consulting fees from: Abbvie, Amgen, Arena, Biocon, Biogen, Celltrion Healthcare, CTMA, Ferring, Galapagos/AlfaSigma, GutyCare/Resilience Janssen, Lilly, MSD, Nexbiome, Pileje, Pfizer, Roche, Sandoz, Takeda et Tillotts. Lecture fees from: Abbvie, Amgen, Biogen, Celltrion Healthcare Galapagos/AlfaSigma, Ferring, Janssen, Lilly, Mayoli-Spindler, MSD, Nordic Pharma, Norgine, Pfizer, Roche, Takeda, Tillotts and Vifor Pharma. Research grants/fundings from: Abbvie, Celltrion Healthcare, Janssen, Lessaffre, Lilly, Pfizer, Sandoz and Takeda Caillo, Ludovic: Abbvie, Amgen, Celltrion, Ferring, Fresenius, Lilly, Jonhson & Jonhson, MSD, Pfizer, Takeda, Sandoz Vuitton, Lucine: abbvie amgen J&J Pfizer Takeda Lilly MSD Mayoli Ferring Dr Falk Alpha Sigma Altwegg, Romain: Advisory boards from Abbvie, Takeda, Johnson and Johnson, Lilly, Alphasigma, Celltrion, Pfizer, Amgen, Biogen, Sandoz, Ferring Hebuterne, Xavier: Xavier Hébuterne reports clinical research funding from Abbvie, Abivax, Amgen, Celltrion, Lilly, Fresenius-Kabi, J&J, InDex Pharmaceuticals, Pfizer, Prometheus, MSD, Roche, Takeda, serving on advisory boards for Abbvie, Biogen, Celltrion, Lilly, J&J, and participating in lectures and educational activities for Abbvie, Amgen, Celltrion, Lilly, Fresenius-Kabi, Galapagos, J&J, MSD, Nestlé Health Sciences, Nutricia, Pfizer, Tillots, Takeda. Ernst, Olivier: No conflict of interest Meunier, Paul: No conflict of interest for this study Laurent, Valerie: No conflict of interest for this study Laharie, David: Personal Fees: Board, consulting and lecture fees from Abbvie, Alfasigma, Amgen, Biocon, Celltrion, Ferring, Fresenius-Kabi, Johnson & Johnson, Lilly, MSD, Pfizer, Sandoz and Takeda Vicaut, Eric: No conflict of interest for this study 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, and lecture: Abbvie, Alfasigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots