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Observational Study
. 2025 Mar;13(2):229-239.
doi: 10.1002/ueg2.12712. Epub 2024 Dec 8.

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

D Magalhaes  1 , M Santiago  2   3 , M Patita  4 , B Arroja  5 , P Lago  6 , I Rosa  7 , H T Sousa  8   9 , P Ministro  10 , I Mocanu  4 , A Vieira  4 , J Castela  7 , J Moleiro  7 , J Roseira  8   9 , C Eugenia  10 , P Sousa  10 , F Portela  11 , L Correia  12 , S Dias  3 , J Afonso  1 , S Danese  13   14 , L Peyrin-Biroulet  15 , C C Dias  16   17 , F Magro  1   2   3   18   19 ; GEDII
Collaborators, Affiliations
Observational Study

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

D Magalhaes et al. United European Gastroenterol J. 2025 Mar.

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.

Keywords: Crohn's disease; fecal calprotectin; infliximab; lactoferrin’; lipocalin‐2; neutrophil elastase; resistin; serum neutrophil biomarkers.

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Conflict of interest statement

Author Fernando Magro served as speaker and received honoraria from Merck Sharp & Dohme, Abbvie, Vifor, Falk, Laboratórios Vitória, Ferring, Hospira and Biogen. All other authors declare no relevant competing interests.

Figures

FIGURE 1
FIGURE 1
Patient disposition and blood collection points.
FIGURE 2
FIGURE 2
Changes in serum (ng/mL; panels A–D) and fecal (μg/g; panel E) concentrations of each biomarker over up to 2 years of infliximab maintenance treatment. Error bars: Standard deviation. p‐values below 0.05 were considered statistically significant.
FIGURE 2
FIGURE 2
Changes in serum (ng/mL; panels A–D) and fecal (μg/g; panel E) concentrations of each biomarker over up to 2 years of infliximab maintenance treatment. Error bars: Standard deviation. p‐values below 0.05 were considered statistically significant.
See this image and copyright information in PMC

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