Factors Influencing Clinical and Radiological Response in Perianal Disease: Results from a Real-World Cohort Treated with Anti-TNF Therapy

<b>Background</b>: Perianal Crohn's disease (PD) remains a major therapeutic challenge, with heterogeneous responses to anti-TNF therapy and limited real-world data on predictors of long-term outcomes. This study aimed to evaluate clinical and radiological response to anti-TNF therapy initiated exclusively for PD and to identify factors associated with treatment response. <b>Methods:</b> A retrospective study was conducted in a cohort of 65 patients with PD treated with anti-TNF. The primary endpoint was clinical response assessed at weeks 24, 52, and 60 months. It was defined as a ≥50% reduction in drainage, and remission as complete absence of drainage. Radiological response was assessed by magnetic resonance imaging at the same time points whenever feasible. Multivariate logistic regression analyses were performed to identify independent predictors of response. <b>Results:</b> At week 24, 84.6% of patients achieved a clinical response, while radiological response was observed in 30.8%. At week 52, clinical and radiological response rates were 80.0% and 52.3%, respectively. At 60 months, 61.5% maintained clinical response and 46.1% radiological response. Among patients who responded at week 24, 90.7% maintained response at week 52, with a secondary loss of response rate of 9.3%. Multivariate analysis identified absence of antineutrophil cytoplasmic antibodies (ANCA) as an independent predictor of clinical response at week 52 (OR 0.06, 95% CI 0.006-0.59; <i>p</i> = 0.01). No significant associations were observed between anti-TNF serum levels and clinical or radiological outcomes. <b>Conclusions</b>: In this real-world cohort of patients initiating anti-TNF exclusively for PD, early response (week 24) emerged as a potential marker of long-term outcomes, highlighting the importance of early reassessment and individualized therapeutic strategies.