Perianal fistulizing Crohn's disease: emerging biology, therapeutics, and roadmap for precision treatment.

Perianal fistulizing Crohn's disease (PFCD) remains difficult to treat despite integrated medical and surgical management, and no validated biomarkers are currently available to guide pharmacological treatment selection. Recent single-cell, spatial, and multiomic studies have identified immune, stromal, epithelial, and microbial features across fistula tissue and rectal mucosa, expanding the biological characterization of PFCD. In this review, we examine how these molecular advances refine the biological understanding of PFCD and inform the evaluation of current and emerging pharmacological strategies. We critically assess the efficacy, safety, and strength of clinical evidence across distinct therapeutic approaches. We also discuss how molecular insights could support biomarker development for patient stratification and treatment selection, alongside anatomical phenotype, surgical context, and standardized multidimensional assessment of fistula healing.