P0832Recapturing disease control with subcutaneous infliximab after a drug holiday following intravenous infliximab induction: A post hoc analysis of LIBERTY-CD and -UC studies

Abstract Background Patients (pts) with Crohn’s disease (CD) or ulcerative colitis (UC) receiving infliximab (IFX) may undergo a treatment interruption (‘drug holiday’) for clinical or non-clinical reasons.1,2 Upon disease recurrence, reinitiating IFX intravenously (IV) may be considered with caution, but there are no data on starting subcutaneous (SC) IFX treatment after a drug holiday. This analysis evaluated the efficacy and safety of starting IFX SC in pts randomised to the placebo (PBO) maintenance arm in the Phase 3 LIBERTY studies who had previously completed IFX IV induction and subsequently experienced a ≥ 16-week drug holiday before starting IFX SC due to disease progression. Methods In LIBERTY-CD and -UC, responders to IFX IV induction were randomised at Week (W) 10 to receive either IFX SC 120 mg or PBO every other week up to W54.3 From W22, pts could receive IFX SC 240 mg through W102 if they lost response or at physician’s discretion. Data were aligned to IFX SC start (time zero). Clinical, biochemical, and endoscopic endpoints, treatment persistence, serum IFX levels, immunogenicity, and treatment-emergent adverse events were evaluated throughout the treatment period. Multivariable regression was used to identify potential predictors of response following IFX SC start in 51 CD and 77 UC pts from the PBO arms. Results The median (IQR) time from the last IFX IV induction to IFX SC start was 16 (16–24) weeks in both CD and UC. Early clinical responses were observed by 8±2 weeks after IFX SC start and maintained throughout the study (CD, 92.3%; UC, partial clinical response, 96.6%). Faecal calprotectin remission and endoscopic response/improvement were achieved in 61.1%/64.0% of CD and 65.2%/68.8% of UC, respectively, at the end of treatment. Persistence at treatment end was 72.3% in CD and 61.9% in UC. Serum IFX levels notably increased after IFX SC initiation compared to preinitiation trough levels and remained stable through W102. Among pts who were ADA-positive prior to IFX SC start, 68.2% (CD) and 61.9% (UC) remained on therapy through study end, compared with 83.6% and 50.0% of ADA-negative pts, respectively. In CD, predictors of clinical remission at 24±2 weeks after IFX SC start included clinical remission at W10 and IFX ≥20 μg/mL at 16 weeks after IFX SC start. In UC, predictors of partial clinical remission at 40±2 weeks after IFX SC start included lower partial Mayo score at W10, lower C-reactive protein at IFX SC start, and IFX ≥22 μg/mL at 8 weeks after IFX SC start. No significant safety concerns were observed after IFX SC start. Conclusion IFX SC 240 mg restored and maintained response in most CD and UC pts with sustained efficacy, safety, and persistence through W102. Early remission and higher IFX levels predicted success. References: 1. Normatov I, Fluxa D, Wang JD, et al. Real-world experience with proactive therapeutic drug monitoring during infliximab reintroduction. Crohns Colitis 360. 2021;3(3):otab048. 2. Rubin DT. Restarting biologic agents after a drug holiday. Gastroenterol Hepatol (N Y). 2019;15(11):612–615. 3. Colombel JF, Sandborn WJ, Schreiber S, et al. Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn’s disease and ulcerative colitis: 2-year results from open-label extensions of two randomized controlled trials (LIBERTY). J Crohns Colitis. 2025;19(6):jjaf060. Conflict of interest: Dubinsky, Marla C: Personal Fees: Consultant or Advisory Board: Abbvie, Abivax, Astra Zeneca, BMS, Celltrion Inc., Gilead, Genentech, Janssen, Johnson and Johnson, Lilly, Merck, Pfizer, Prometheus Biosciences, Sanofi, Spyre, Target RWE, Takeda. Other: Shareholder, Co-founder, Board of Directors of Trellus Health, Co-Founder Mi Test Health. Sands, Bruce E: Grant: Janssen. Personal Fees: Abivax SA, Abbvie, Adiso Therapeutics, Agomab Therapeutics, Alimentiv, Amgen, AnaptysBio, AstraZeneca, Biora Therapeutics, Boehringer-Ingelheim, Bristol Myers Squibb, Celltrion Inc., ClostraBio, Cytoki Pharma, EcoR1 Capital, Eli Lilly and Company, Enthera, Equilium Inc., Ensho Therapeutics, Evommune, Ferring, Galapagos, Genentech Inc., Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Immunyx Pharma Ltd., Index Pharmaceuticals, Innovation Pharmaceuticals, Janssen, Janssen Biotech, Janssen Pharmaceutica NV, Janssen Research & Development LLC, Janssen Scientific Affairs LLC, Janssen-Cilag PTY, Ltd., Johnson and Johnson, Kaleido, Kallyope, Kyowa Kirin, Inc., Merck & Co., Microba, Microbiotica Limited, Mirador Therapeutics, Morphic Therapeutic, MRM Health NV, Palisade Therapeutics, Pfizer Inc., Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics Inc., Q32 Bio, Sanofi, Sorriso Therapeutics, Surrozen, Takeda, Target RWE, Teva, TLL Pharmaceutical, Tr1x, Union Therapeutics, Ventyx Biosciences. Non-financial Support: Janssen, Pfizer, Lilly, Takeda, Bristol Myers Squibb. Other: Stock/Stock Options from Ventyx Biosciences. Abraham, Bincy: Consultant for: AbbVie, Celltrion Inc., Lilly, Johnson and Johnson, Pfizer, Ironwood, Sanofi, Merck, Genentech, Takeda. Schreiber, Stefan Wolfgang: Personal Fees: AbbVie, Alfasigma, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Inc., Falk, Ferring, Fresenius Kabi, Galapagos, Gilead, IMAB, Janssen, Lilly, MSD, Mylan, Novartis, Pfizer, Protagonist, Provention Bio, Roche, Sandoz/Hexal, Shire, Takeda, Theravance. Dr. Myung, Noehyun: Employee of Celltrion, Inc. Jeong, Ae Lee: Employee of Celltrion, Inc. Lee, Young Nam: Employee of Celltrion Inc. Owns company stock and stock options. Colombel, Jean-Frédéric: Grant: AbbVie, Janssen Pharmaceuticals, Takeda, Prometheus, Bristol Myers Squibb. Lectures from: AbbVie, Roche, Takeda. Other: AbbVie, Amgen, AnaptysBio, Allergan, Apini, Arena Pharmaceuticals, Astellas, Boehringer Ingelheim, Bristol Myers Squibb, candidrx, Celgene, Celltrion Inc., Clearview Curogen, Eli Lilly, Envision Pharma Ferring Pharmaceuticals, Galmed Research, GlaxoSmithKline, Roche, Janssen Pharmaceuticals, Kaleido Biosciences, Immunic, Iterative Scopes, Landos, Microba Life Science, Merck, Mirador, Novartis, Otsuka Pharmaceutical, Owkin, Pfizer, Protagonist Therapeutics, Sanofi, Sun Pharma, Takeda, Teva, TiGenix. Stock options in Intestinal Biotech Development.