P1259Risk factors for intestinal fibrosis on mucosal biopsies in patients with inflammatory bowel disease in Sweden: a cohort study

Abstract Background Intestinal fibrosis is a complication of inflammatory bowel disease (IBD), but its risk factors remain unclear, particularly in the modern treatment era. We aimed to identify potential risk factors for intestinal fibrosis in Crohn’s disease (CD) and ulcerative colitis (UC). Methods We conducted a nationwide, population-based cohort study including all patients with incident CD and UC in Sweden from 1990 to 2023. Patients were identified from the National Patient Register and a gastrointestinal histopathology cohort (ESPRESSO). The outcome was intestinal fibrosis, identified through Systematized Nomenclature of Medicine (SNOMED) codes from ESPRESSO. Cox proportional hazards models were used to estimate hazard ratios (HRs) of potential risk factors associated with the development of intestinal fibrosis, with 95% confidence intervals (CIs). We also performed an analysis in a subset of patients diagnosed with IBD during 2007–2023 to explore the associations between medication use and fibrosis risk. Results Among 26,328 patients with incident CD, we identified 653 patients with intestinal fibrosis during a median follow-up of 4.0 years (interquartile range IQR 1.0–10.9). Older age at CD diagnosis (HR = 1.00; 95% CI: 1.00–1.01), autoimmune disease (HR = 1.32 1.05–1.67), primary sclerosing cholangitis (PSC, HR = 2.12 1.29–3.48), liver fibrosis/cirrhosis (HR = 1.63 0.99–2.70), and IBD-related surgery (HR = 2.33 1.94–2.79) was associated with fibrosis in patients with CD (figure1). During a median follow-up of 5.4 years (IQR: 1.7–11.1), 1,004 out of 52,039 patients with incident UC had intestinal fibrosis. In UC, older age at diagnosis (HR = 1.01 1.00–1.01), autoimmune disease (HR = 1.25 1.03–1.54), and PSC (HR = 1.85 1.35–2.53) were associated with an increased fibrosis risk (figure 1). Additionally, use of proton pump inhibitors (PPI, HR = 1.90 1.38–2.62) and 5-aminosalicylic acid (5-ASA, HR = 1.38 1.03–1.85) during the follow-up were associated with fibrosis in patients with CD, whereas use of anti-TNFα and other biologics (HR = 1.66 1.07–2.59) and corticosteroids (HR = 1.60 1.07–2.40) were linked to fibrosis in patients with UC. Conclusion Among patients with CD, age at diagnosis, autoimmune diseases, PSC, liver fibrosis/cirrhosis, and IBD-related surgery were associated with fibrosis, whereas in patients with UC, age at diagnosis, autoimmune diseases, and PSC were linked to fibrosis. Multiple medications used during follow-up were also linked to fibrosis development in CD (PPIs and 5-ASA) and UC (anti-TNFα and other biologics, and corticosteroids). Conflict of interest: Sun, Jiangwei: No conflict of interest Li, Meiling: No conflict of interest Roelstraete, Bjorn: No conflict of interest Rieder, Florian: Personal Fees: Adiso, Adnovate, Agomab, Allergan, AbbVie, Arena, Astra Zeneca, Boehringer-Ingelheim, Celgene/BMS, Celltrion, CDISC, Celsius, Cowen, Ferring, Galapagos, Galmed, Genentech, Gilead, Gossamer, Granite, Guidepoint, Helmsley, Horizon Therapeutics, Image Analysis Limited, Index Pharma, Landos, Jannsen, Koutif, Mestag, Metacrine, Mopac, Morphic, Organovo, Origo, Palisade, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Sanofi, Surmodics, Surrozen, Takeda, Techlab, Teva, Theravance, Thetis, UCB, Ysios, 89Bio Veress, Gabor: No conflict of interest Osagie-Igho, Ebuwa: Employed by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may hold stock options in Merck & Co., Inc., Rahway, NJ, USA Lawlor, Garrett: Employed by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may hold stock options in Merck & Co., Inc., Rahway, NJ, USA Bergman, David: No conflict of interest Halfvarson, Jonas: Grant support: Swedish Foundation for Strategic Research (RB13-0160 to J.H.), the Swedish Research Council (2020-02021 to J.H.), the Örebro University Hospital research foundation (OLL-890291 to J.H.), NordForsk (90569 to J.H.) and Vinnova ( 2019-01185 to JH and 2024-01155 co-applicant), IHI, EU, INTERCEPT (Grant agreement number 101194780, co-applicant), miGut-Health, HORIZON-HLTH-2022, EU (Grant Agreement 101095470, Co-applicant), 3TR, IMI 2, EU, (Grant agreement number 831434, Co-applicant), Janssen, MSD, and Takeda. Consulting and/or advisory board fees from: AbbVie, Alfasigma, Aqilion, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead Sciences, Hospira, Index Pharmaceuticals, Janssen, Johnson &amp Johnson, MEDA, Medivir, Medtronic, Merck, Merck Sharp &amp Dohme, Novartis, Pfizer, Prometheus Laboratories Inc., Sandoz, Shire, STADA, Takeda, Thermo Fisher Scientific, Tillotts Pharma, Vifor Pharma, UCB and speaker’s fees from: AbbVie, Alfasigma, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Galapagos, Gilead, Hospira, Janssen, Johnson & Johnson, Merck Sharp &amp Dohme, Novartis, Pfizer, Shire, Takeda, Thermo Fisher Scientific, Tillotts Pharma and research grant support from Janssen, Merck Sharp &amp Dohme and Takeda. Olen, Ola: Karolinska Institutet has received research grants from Pfizer, Janssen, AbbVie, Takeda, Ferring, Bristol Myers Squibb, and Alfasigma for projects led by Olén. Ola Olén has also received fees for lectures from Pfizer, Janssen, Bristol Myers Squibb, and Takeda. Liu, Gui: Employed by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may hold stock options in Merck & Co., Inc., Rahway, NJ, USA Ludvigsson, Jonas: JFL has received financial support from MSD to develop a paper reviewing national healthcare registers in China and has a research collaboration on fibrosis in IBD. JFL has a research collaboration on celiac disease with Takeda.