Magalhaes, D.Santiago, M.Patita, M.Arroja, B.Lago, P.Rosa, I.Sousa, Helena TavaresMinistro, P.Mocanu, I.Vieira, A.Castela, J.Moleiro, J.Roseira, J.Eugenia, C.Sousa, P.Portela, F.Correia, L.Dias, S.Afonso, J.Danese, S.Peyrin‐Biroulet, L.Dias, C. C.Magro, F.2025-01-102025-01-102024-12-082050-64062050-6414http://hdl.handle.net/10400.1/26604Background and aims: Predicting the treatment outcomes of biological therapies is an unmet need in Crohn's Disease. In this study, we explored the potential of serum neutrophil-related biomarkers to predict infliximab therapeutic results and disease progression in Crohn's Disease patients, over a 2-year period, in a real-world setting. Methods: The study included 100 asymptomatic Crohn's Disease patients in the IFX maintenance phase from the prospective, observational, multicenter DIRECT study. Patients were categorized according to a composite outcome reflecting progression that included surgery, hospitalizations, new fistulae, abscess or stricture, and drug treatment escalation. Serum neutrophil elastase, lipocalin-2, lactoferrin, and resistin (non-neutrophil control) were analyzed via multiplex magnetic bead assays at multiple touchpoints. Fecal calprotectin was assessed by ELISA. Results: Over up to 2 years of follow-up, serum biomarkers did not differentiate between the composite outcome groups, whereas fecal calprotectin was significantly higher in patients with worse outcomes. During the infliximab maintenance phase, there was a significant, sustained reduction of neutrophil elastase (p < 0.001), lipocalin-2 (p < 0.001), and lactoferrin (p < 0.001), but not of resistin, despite stable neutrophil levels. Correlations between NE and NGAL levels were strong (Pearson correlations 0.75-0.85); all other correlations were of small magnitude. Conclusion: Our real-world data do not support using serum neutrophil elastase, lipocalin-2, or lactoferrin concentrations as predictors of treatment outcomes or disease evolution in infliximab -treated Crohn's Disease patients. On the other hand, the sustained decrease in biomarkers over time suggests that neutrophil stabilization might be an additional infliximab mechanism of action.engCrohn's diseaseFecal calprotectinInfliximabLactoferrinL'ipocalin-2Neutrophil elastaseResistinSerum neutrophil biomarkersjournal article10.1002/ueg2.12712