P1096Randomised controlled trial of continued intravenous versus switching to subcutaneous infliximab in inflammatory bowel disease: the Subcutaneous Infliximab Switch Study (SISS).

Abstract Background Loss of response to intravenous (IV) infliximab occurs over time due to subtherapeutic levels and immunogenicity 1. Subcutaneous (SC) infliximab produces higher, more stable trough concentrations and may reduce treatment failure 2-3. Observational studies show high effectiveness and tolerability of SC infliximab 4, but whether switching inflammatory bowel disease (IBD) patients in stable steroid-free remission from IV to SC improves long-term disease control is unknown. Methods We conducted a prospective, multicentre, randomised controlled basket trial in IBD patients in ≥ 6 months of steroid-free clinical and biochemical remission. Participants were randomised 1:1, stratified by Crohn’s disease (CD) and ulcerative colitis (UC), to continue IV infliximab or switch to SC infliximab. The primary endpoint was treatment failure at week 48 (modified intention-to-treat), defined as clinical relapse, discontinuation due to adverse event, therapeutic drug level failure, or patient withdrawal. Secondary endpoints included clinical relapse, biochemical flare, treatment failure by disease subtype, and per-protocol analyses. Participants completing 48-week follow-up by 2 Nov 2025 were analysed. Results A total of 199 patients were enrolled (CD n = 125; UC n = 74; median age 37; 43% female). Of these, 100 remained on IV and 99 switched to SC. Treatment failure was lower with SC (14/99, 14.1%) versus IV (35/100, 35.0%; absolute risk reduction (ARR) 20.9%, 95%CI 9.2–32.5; P = 0.001). In CD, switching significantly reduced treatment failure (12.9% vs 36.5%; ARR 23.6%, 95%CI 9.1–38.1; P = 0.002). In UC, a numerical reduction was observed (16.2% vs 32.4%; ARR 16.2%, 95%CI –3.0–35.4; P = 0.10). Benefit was greatest in patients on standard-dose 5 mg/kg q8w (P = 0.002) and not seen in dose-escalated regimens (P = 0.32). Anti-drug antibodies developed in three patients, all on IV. Adverse and serious adverse event rates were similar between groups. On multivariate analysis, SC therapy (HR 0.36, 95%CI 0.19–0.66; P = 0.001), corticosteroid exposure (HR 0.52, 95%CI 0.29–0.95; P = 0.026), and lower baseline white cell count (HR 1.16, 95%CI 1.00–1.35; P = 0.05) were associated with maintenance of remission; bio-exposure, baseline escalated infliximab dosing, immunomodulator use, age and gender were not (P 0.05). Conclusion Switching from IV to SC infliximab in IBD patients in sustained remission resulted in superior maintenance of remission at 48 weeks (significant in CD and numerical in UC) without increased adverse events or immunogenicity. Anti-drug antibodies occurred more often with IV than SC infliximab. ANZCTR: ACTRN12621001498886. References: 1. Louis E, et al. Withdrawal of infliximab or concomitant immunosuppressant therapy in patients with Crohn’s disease on combination therapy (SPARE): a multicentre, open-label, randomised controlled trial. Lancet Gastroenterol Hepatol. 2023 Mar;8(3):215-227. 2. Schreiber S, et al. Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease. Gastroenterology. 2021 Jun;160(7):2340-2353. 3. Chetwood JD, et al. Meta-Analysis: Intravenous Versus Subcutaneous Infliximab in Inflammatory Bowel Disease. Aliment Pharmacol Ther. 2025 Aug;62(4):380-388. 4. Chetwood JD, et al. Intravenous Versus Subcutaneous Infliximab in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. J Crohns Colitis. 2024 Sep 3;18(9):1440-1449. Conflict of interest: Chetwood, John: Speaker fees: Novartis, Eli Lilly, Dr Falk Pharma, Johnson&Johnson Redmond, Diane: No conflict of interest Kermeen, Melissa: No conflict of interest Kariyawasam, Viraj: No conflict of interest Thin, Lena: No conflict of interest Lightowler, Daniel: Speaker Fees: Pfizer, DrFalk, Eli Lily Advisory Board: AbbVie, Eli Lily, Menarini, Janssen, AGPAL Travel: Pfizer, Celgene, Allergen, Janssen, AbbVie Research Support: Janssen, Ferring Education: DrFalk, AbbVie, Janssen, Pfizer Corte, Crispin: Grants: Ferring, GESA Consulting: Abbvie, Ferring, Celltrion, Chiesi, Janssen, Takeda. Support for travel for meetings to support study: Pfizer, Takeda, Celltrion, Chiesi, Ferring, Falk. Ding, Nik John Sheng: No conflict of interest Ward, Mark G.: No conflict of interest Little, Robert: No conflict of interest Kwan, Vu: No conflict of interest De Cruz, Peter: No conflict of interest Lee, Lok Hin: No conflict of interest Duong, Tuan Anh: No conflict of interest Lee, Esther: No conflict of interest Menon, Shankar: No conflict of interest Khaing, Myat Myat: No conflict of interest Beswick, Lauren: No conflict of interest Lagumbay, Lea: No conflict of interest Walker, Timothy: No conflict of interest Paramsothy, Sudarshan: SP has served as a consultant for Finch Therapeutics and has received speaker / advisory board fees from AbbVie, Dr Falk Pharma, Ferring, Janssen and Takeda. Leong, Rupert: RWL reports personal fees from AbbVie, personal fees from Aspen, personal fees from Ferring, grants and personal fees from Hospira/ Pfizer, grants and personal fees from Janssen, grants and personal fees from Takeda, grants from Shire, personal fees from Celgene, personal fees from Dr Falk Pharma, personal fees from Novartis, personal fees from MSD, personal fees from Chiesi, personal fees from BMS, personal fees from Glutagen, outside the submitted work.