Tumor Necrosis Factor Inhibitors May Have Limited Efficacy for Complex Perianal Fistulas Without Luminal Crohn's Disease

Background: Complex perianal fistulas occurring in the absence of luminal inflammation (isolated perianal disease, IPD) may represent a specific phenotype of Crohn's disease (CD).

Aim: We assessed the effectiveness of tumor necrosis factor (TNF)-antagonists in patients with IPD compared to those with perianal CD (PCD) with luminal inflammation.

Methods: Patients were identified through our institutional radiology database and were classified as PCD or IPD based on the presence or absence of luminal inflammation by ileocolonoscopy and abdominal enterography. Consecutive adults (> 17 years) with recurrent IPD who were treated with TNF antagonists were matched by age and gender to patients with complex PCD (1:2 ratio). Fistula remission was defined as an absence of fistula drainage. Surgery-free survival was assessed by Cox proportional hazard models.

Results: Twenty-two patients with IPD treated with a TNF antagonist were compared with 44 matched patients with PCD. A similar proportion of patients with IPD and PCD were treated with concomitant immunomodulators (55% vs. 66%) and underwent examinations under anesthesia prior to therapy (36% vs. 46%). Fistula remission at 3, 6, and 12 months was lower for the IPD cohort: 9.5% versus 34%; 19% versus 39%; and 19% versus 43%. Surgical intervention after initiating anti-TNF therapy was more common for patients with IPD (HR 3.99: 95% CI, 1.62-9.83; p = 0.0026).

Conclusions: Fewer patients with IPD achieved fistula remission, and more required surgical intervention after anti-TNF therapy, suggesting that TNF antagonists may not be as effective in these patients.