Background: Accurate assessment of tract-specific inflammatory activity remains difficult in perianal fistulizing Crohn's disease (pfCD), as current clinical and imaging indices incompletely reflect local activity.
Aims: To evaluate fistula calprotectin (FiCP) as a tract-specific biomarker, focusing on diagnostic accuracy, associations with histological, clinical, and radiological indices, longitudinal responsiveness, and local infliximab exposure.
Methods: In this single-center observational study (April 2023-July 2025; n = 105), patients with pfCD provided fistula exudate samples during surgical or outpatient assessment. FiCP concentrations were quantified by ELISA and correlated with histological inflammation, the Perianal Disease Activity Index (PDAI), the MRI-based modified Van Assche Index (mVAI), and total fistula volume (TFV). Diagnostic performance was analysed using receiver operating characteristic (ROC) curves with DeLong comparison, and treatment responsiveness was evaluated longitudinally using the standardised response mean (SRM). Serum and local infliximab concentrations were measured using ELISA.
Results: FiCP levels were significantly higher in fistulas with severe versus mild histological inflammation (p = 0.021) and in clinically or radiologically active tracts (both p < 0.001). FiCP correlated with PDAI (R = 0.61), mVAI (R = 0.40), and local infliximab concentration (R = -0.64). FiCP discriminated active from quiescent fistulas (AUC 0.843; 95% CI 0.758-0.928) and retained diagnostic value in patients with normal CDAI scores. FiCP levels declined significantly after therapy and showed greater responsiveness than PDAI and TFV.
Conclusions: FiCP represents a minimally invasive, tract-specific biomarker that mirrors local inflammatory activity and dynamically tracks treatment response in pfCD. Multicenter validation is warranted to define its clinical utility.
Keywords: Crohn's disease; biomarker; calprotectin; disease activity; perianal fistula.
© 2026 John Wiley & Sons Ltd.