Abstract
BACKGROUND 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.