Bravo, Francisco DamianFrancisco DamianBravoMacpherson, Jamie AJamie AMacphersonSlack, EmmaEmmaSlackPatuto, NicolaNicolaPatutoCahenzli, JuliaJuliaCahenzliMcCoy, KathleenKathleenMcCoyMacpherson, AndrewAndrewMacpherson0000-0002-7192-0184Juillerat, PascalPascalJuillerat2024-10-052024-10-052021-02-15https://boris-portal.unibe.ch/handle/20.500.12422/57202INTRODUCTION The development of biomarkers to guide management of anti-tumor necrosis factor (TNF) agents in patients with inflammatory bowel disease (IBD) is an unmet need. We developed an in vitro blood assay to predict patient long-term outcome with the anti-TNFα agent infliximab (IFX). METHODS Patients with IBD were classified according to the shedding of an L-selectin (CD62L) from the surface of their granulocytes in whole blood. CD62L shedding was quantified by flow cytometry before and after drug administration. A clinical data collection from June 2012 to August 2017 with blinded IFX management was aimed at validating the long-term predictive value of this test. RESULTS Among 33 patients with IBD (17 Crohn's disease and 5 ulcerative colitis), 22 were predicted functional responders (PFR) and 11 were predicted as nonresponders (NR) according to the in vitro test. Five years after study initiation, 72% of PFR were still treated with IFX (vs 27% in the NR group; P < 0.05), with a median time spent under IFX of 45 vs 12 months (P = 0.019), respectively. Thirty-five medicosurgical events occurred with a median time to first event of 3 vs 30 months (P = 0.023), respectively. Our assay was the best independent predictor of staying long term on IFX (P = 0.056). DISCUSSION An assay-based in vitro test for functional blockade of TNFα (CD62L shedding) provides an excellent long-term (at 3-5 years) independent predictor of durable use of IFX in patients with IBD. Testing patients could personalize decision making to significantly reduce costs and risk of adverse events and complications.en600 - Technology::610 - Medicine & healtharticle10.48350/1590873373515410.14309/ctg.0000000000000298