Journal Article

Serum Neutrophil Biomarkers to Predict Crohn's Disease Progression and Infliximab Treatment Outcomes

Arroja, B., Sousa, H. T., Lago, P., Ministro, P., Portela, F., Magalhaes, D., Dias, S., Sousa, P., Mocanu, I., Eugenia, C., Magro, F., Vieira, A., Roseira, J., Peyrin‐Biroulet, L., Castela, J., Danese, S., Dias, C. C., Santiago, M., Rosa, I., Correia, L., Patita, M., Moleiro, J., Afonso, J.

2025

Overview

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.

• Publisher: John Wiley and Sons Inc
• Subject: Adult / Biomarkers - blood / Crohn Disease - blood / Crohn Disease - diagnosis / Crohn Disease - drug therapy / Crohn's disease / Disease Progression / fecal calprotectin / Feces - chemistry / Female / Follow-Up Studies / Gastrointestinal Agents - therapeutic use / Humans / Inflammatory Bowel Disease / infliximab / Infliximab - therapeutic use / lactoferrin / Lactoferrin - blood / Leukocyte Elastase - blood / Leukocyte L1 Antigen Complex - analysis / Leukocyte L1 Antigen Complex - metabolism / Lipocalin-2 - blood / lipocalin‐2 / Male / Middle Aged / neutrophil elastase / Neutrophils - metabolism / Original / Prospective Studies / resistin / Resistin - blood / serum neutrophil biomarkers / Treatment Outcome / Young Adult