P0781Efficacious Transitioning from Ustekinumab to a Selective IL23 p19 Inhibitor in Patients with Endoscopic Disease Activity (SHELTER)

Abstract Background In clinical practice, patients with inflammatory bowel disease (IBD) not achieving endoscopic remission with the IL12/23 p40 inhibitor ustekinumab (UST) may be switched to an IL23 p19 inhibitor. This therapeutic transition is based on clinical trial data suggesting that p19 inhibitors are more potent in achieving endoscopic endpoints.1,2 Methods We included adult patients with Crohn’s disease (CD) or ulcerative colitis (UC), who were treated with subcutaneous UST 90mg every four or every eight weeks and this for at least 16 weeks and switched to a p19 inhibitor due to ongoing endoscopic disease activity Simplified Endoscopic Score of Crohn’s Disease (SES-CD) 5 for CD (SES-CD 3 for isolated ileitis) or endoscopic Mayo score (EMS) ≥2 for UC. All patients had at least one year of follow-up and underwent endoscopy at baseline and after one year of the selected p19 inhibitor treatment. Patients with an ostomy, ileal pouch-anal anastomosis, or prior exposure to a p19 inhibitor were excluded. The primary endpoints were the evolution of the endoscopic scores (SES-CD, the EMS, or the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score), based on Wilcoxon Signed-Rank testing. We also evaluated endoscopic remission in CD, endoscopic improvement in UC, and PRO2 clinical remission in both CD and UC (definitions in Fig 1 median (interquartile range, IQR) age 46 (41-62) years; 9 patients in PRO2 clinical remission] were included. One year after initiating a p19 inhibitor (all risankizumab), the median (IQR) SES-CD score dropped numerically from 7 (5-8) to 5 (4-8) (p = 0.124; Fig 1). Five CD patients (19%) achieved endoscopic remission after one year. A total of seven patients with UC 3 men; median (IQR) age 45 (38-53) years; 3 patients in PRO2 clinical remission were included. One year after switching to a p19 inhibitor (all mirikizumab, four patients with extended intravenous induction), the median (IQR) EMS and UCEIS score dropped significantly from, respectively, 2 (2-3) to 1 (0-2) (p = 0.034) and 3 (3-4) to 0 (0-2) (p = 0.021; Fig 2). Five UC patients (71%) showed endoscopic improvement after one year of treatment. No serious adverse events were observed. Conclusion Taking into account the relatively small sample size, a clear trend of endoscopic improvement was observed in patients with IBD one year after switching from UST to a selective IL23 p19 inhibitor. This SHELTER cohort will further be expanded. References: 1. Peyrin-Biroulet L, Chapman JC, Colombel J-F, et al. Risankizumab versus Ustekinumab for Moderate-to-Severe Crohn’s Disease. N Engl J Med. 2024;391:213-223. 2. Panaccione R, Feagan BG, Afzali A, et al. GALAXI 2 406(10501):358-375. Conflict of interest: 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 Beeckmans, Dorien: none Brams, Stephanie: No conflict of interest Nigro, Melissa: No conflict of interest Eggermont, Elisabeth: No conflict of interest Guedelha Sabino, João: Speaker’s fees: Lilly, Pfizer, Abbvie, Ferring, Falk, Takeda, Janssen, Fresenius, and Galapagos. Consultancy fees: Takeda, Pfizer, Janssen, Ferring, Fresenius, Abbvie, Galapagos, Celltrion, Pharmacosmos, and Pharmanovia. Research support: Galapagos, Viatris, and Eurogenerics. JS is supported by a Senior Clinical researcher grant from the Research foundation – Flanders. Vermeire, Séverine: Grant: AbbVie, Pfizer, Takeda, J&J, Galapagos Personal Fees: AbbVie - AbolerIS Pharma - AgomAb - Alimentiv - Arena Pharmaceuticals - AstraZeneca - Avaxia- BMS - Boehringer Ingelheim - Celgene - CVasThera - Dr Falk Pharma - Ferring - Galapagos - Genentech-Roche - Gilead - GSK - Hospira - Imidomics - Janssen - J&J - Lilly - Materia Prima - MiroBio - Morphic - MrMHealth - Mundipharma - MSD - Pfizer - Prodigest - Progenity - Promakhos Therapeutics - Prometheus - Robarts Clinical Trials - Second Genome - Shire - Surrozen - Takeda - Theravance - Tillots Pharma AG - Zealand Pharma - Other: AbbVie, MSD, Takeda, Ferring, Genentech/Roche, Shire, Pfizer Inc, Galapagos, Mundipharma, Verstockt, Bram: Research support from AbbVie, Biora Therapeutics, Celltrion, Landos, Pfizer, Sanofi, Sossei Heptares/Nxera and Takeda. Speaker’s fees from Abbvie, Agomab, Alfasigma, Biogen, Bristol Myers Squibb, Celltrion, Eli Lily, Falk, Ferring, Galapagos, Materia Prima, Johnson and Johnson, Pfizer, Sandoz, Takeda, Tillots Pharma, Truvion and Viatris. Consultancy fees from Abbvie, Alfasigma, Alimentiv, Anaptys Bio, Applied Strategic, Astrazeneca, Atheneum, BenevolentAI, Biora Therapeutics, Boxer Capital, Bristol Myers Squibb, Domain Therapeutics, Eli Lily, Galapagos, Guidepont, Landos, Merck, Mirador Therapeutics, Mylan, Nxera, Inotrem, Ipsos, Johnson and Johnson, Pfizer, Sandoz, Sanofi, Santa Ana Bio, Sapphire Therapeutics, Sosei Heptares, Takeda, Tillots Pharma and Viatris. Stock options Vagustim and Thethis Pharma.