OP21Evolving risk of colorectal neoplasia in IBD in the biologic era: analysis of the I-CARE European observational prospective cohort.

Abstract Background The risk of colorectal neoplasia (CRN) in inflammatory bowel disease (IBD) is slowly declining, but it is unclear whether this is attributable to benefits of colonoscopy surveillance and/or to the effect of IBD drugs. This is the first cohort addressing these questions by stratification of patients according to the risk level of CRN and adjustment for all CRN risk factors and IBD drugs. Methods The I-CARE cohort is a prospective cohort including IBD patients enrolled by 508 gastroenterologists from 15 countries between 2016 and 2019 (1). Patients provided monthly reports for up to six years including details of IBD treatment, clinical disease activity based on validated scores, colonoscopy procedures, and CRN diagnoses. Physicians yearly confirmed/completed patient’s information. CRN diagnoses were based on pathological reports. Patients were categorized as higher risk (HR) of CRN if eligible for colonoscopy surveillance or as average risk (AR) otherwise (2). Expected incidences of colorectal cancer (CRC) for country, sex and age-specific stratum were based on 2022 IARC estimates (3). The risk of CRN associated with IBD drugs was assessed using marginal structural models adjusting for baseline variables (IBD subtype and location, IBD disease duration, family history of CRC, personal history of PSC and advanced CRN, body mass index, smoking and alcohol status) and time-varying confounders (clinical activity and exposure to IBD drugs). Results Over a median follow-up of 37.0 months (IQR, 35.6-42.3) in 10,105 patients (60.4% Crohn’s disease (CD); HR group, n = 3,064), 81 patients developed CRN (CRC: n = 23; high-grade dysplasia: n = 10; low-grade dysplasia: n = 48). Standardized incidence ratio (SIR) of CRC was 1.84 (95% CI, 1.17-2.76) in the total IBD population, 0.74 (95% CI, 0.24-1.73) in the AR group and 3.12 (95% CI, 1.85-4.94) in the HR group (Table 1). Results did not differ substantially among IBD subtypes and gender. We observed a trend for chemoprevention of CRN for anti-TNFs in the total population (Figure 1), and in all subgroups (only statistically significant in CD, hazard ratio, 0.30; 95% CI, 0.11-0.76). A similar trend was observed for thiopurines at a lesser extent. Aminosalicylates had no impact on the risk, while exposure to methotrexate or vedolizumab was associated with an increased risk of CRN (hazard ratio, 3.02; 95% CI, 1.17-7.81 and 2.16; 95% CI, 1.09-4.29). Conclusion In the biologic era, patients at higher risk of CRN still have a tripled risk of CRC. In the I-CARE cohort, we showed a chemopreventive effect of anti-TNFs against CRN in CD. No protective effect was observed for other IBD treatments, including thiopurines and aminosalicylates. The effect of methotrexate and vedolizumab on CRN must be further explored. References: 1.Peyrin-Biroulet L, Rahier JF, Kirchgesner J, Abitbol V, Shaji S, Armuzzi A, et al. I-CARE, a European Prospective Cohort Study Assessing Safety and Effectiveness of Biologics in Inflammatory Bowel Disease. Clin Gastroenterol Hepatol 2023;21(3):771-788.e10. 2.Gordon H, Biancone L, Fiorino G, Katsanos KH, Kopylov U, Al Sulais E, et al. ECCO Guidelines on Inflammatory Bowel Disease and Malignancies. J Crohns Colitis 2023;17(6):82754. 3.International Agency for research on Cancer. 2022 estimates of the incidence of 36 specific cancer types in 185 countries. https://gco.iarc.fr/today/en/about#about-cancer-today. Conflict of interest: Beaugerie, Laurent: No conflict of interest 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. LECTURE Abbvie, Alfasigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots Baumann, Cédric: Support for meetings: TAKEDA 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 Sebastian, Shaji: Grant: Takeda, Tillots pharma, Biogen, Pfizer, Abbvie, Johnson & Johnson, Olympus -Odin Vision Personal Fees: Tillots, Johnson & Johnson, Olympus Odin Vision, AbbVie, Takeda, Merck, Pharmacosmos, Amgen, Eli Lilly, BMS, Odin Vision Non-financial Support: Tillots, Takeda, AbbVie, Celltrion, Johnson & Johnson, Eli Lilly, Alphasigma, Ferring Pharma Armuzzi, Alessandro: Consulting fees from AbbVie, Abivax, Alfa Sigma, Astra Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Enthera, Ferring, Galapagos, Gilead, Giuliani, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sanofi, Sandoz, Takeda, Teva Pharmaceuticals, Tillots Pharma Speaker’s fees from AbbVie, Abivax, AG Pharma, Alfa Sigma, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Teva Pharmaceuticals Research support from Biogen, MSD, Takeda, and Pfizer Non-financial support from Abbvie, Janssen, MSD, Pfizer, Takeda Viazis, Nikolaos: Nothing to declare Gisbert, Javier: Grant: MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos/Alfasigma, Lilly, Sanofi, STADA, Teva, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, Italfarmaco, and Vifor Pharma. Personal Fees: MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos/Alfasigma, Lilly, Sanofi, STADA, Teva, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, Italfarmaco, and Vifor Pharma. Other: MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos/Alfasigma, Lilly, Sanofi, STADA, Teva, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, Italfarmaco, and Vifor Pharma. Reenaers, Catherine: Grant: Ferring, Janssen, Takeda, Fresenius, Biogen Personal Fees: Ferring, Janssen, Takeda, Fresenius, Abbvie, Galapagos, Pfizer, Celltrion, Thermofisher, BMS, Lilly, Thermofisher Rousseau, Hélène: No conflict of interest Rahier, Jean-François: JF Rahier has received lecture fees from MSD, Pfizer, AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Janssen, Ferring, Falk, Takeda, Amgen, Lilly, Alphasigma advisory board fees from MSD, Pfizer, AbbVie, Takeda, Hospira, Celltrion, Amgen, Mundipharma, Glaxo Smith Kline, Galapagos, Janssen and research support from Takeda, Janssen and AbbVie. Baert, Filip J.: Grant: AbbVie, Amgen, EG, J & J, Takeda. Personal Fees: AbbVie, Abivax, Alpha Sigma, Arena, BMS,Celltrion, Eli Lilly, Falk, Ferring, Fresenius, Galapagos, J & J, Pfizer, Sandoz, Takeda, Vifor. Kirchgesner, Julien: Lecture fees and/or consulting fees from from Abbvie, Amgen, Astrazeneca, Celltrion, Galapagos, Janssen, Lilly, MSD, Takeda, Tillots, Pfizer.