Early TNF antibody therapy protects against disease progression and perianal fistulas in Crohn's disease
Adler J et al, Gut. 2025;74(4):539-546
Re-analysis of the pediatric RISK inception cohort demonstrates that the presence of perianal skin tags, fissures or ulcerations is associated with a high risk of developing perianal fistulas. Early TNF antibody therapy reduced the risk of perianal fistulas in the RISK cohort by 84% and, in the presence of perianal risk stigmata, by as much as 94%.
Background: One in 3 children with Crohn's disease develop perianal fistula complications (PFCs), among the most disturbing and difficult-to-treat disease-related complications. Retrospective evidence suggests PFCs may be preventable.
Objective: The aim of this study was to determine if early antitumour necrosis factor-alpha (anti-TNF⍺) therapy prevents PFC development in a well-characterised prospective cohort of paediatric patients with Crohn's disease who were free from PFC at enrolment.
Design: RISK was a multicentre inception cohort of children newly diagnosed with Crohn's disease. The authors included all patients who had never experienced PFCs 30 days after study enrolment. They conducted nearest-neighbour propensity score-matched triad analyses. Matching was performed to balance patient characteristics across 3 mutually exclusive treatment groups based on therapy prior to either PFC development or the end of the observation period.
Results: Among 873 patients without perianal fistula, 447 matched patients were included (149 per treatment group). The presence of non-penetrating perianal lesions (large skin tags, ulcers and/or fissures) was significantly associated with PFC development, with 4-fold greater odds of PFC (odds ratio [OR] = 4.08, 95% confidence interval [CI]: 1.70–9.78; p = 0.0016). Early anti-TNF⍺ therapy was associated with an 82% decrease in the odds of PFC (OR = 0.18, 95% CI: 0.05–0.66; p = 0.01). Among those with perianal lesions, anti-TNF⍺ therapy was associated with 94% reduced odds of PFC development (OR = 0.055, 95% CI: 0.006–0.50; p = 0.010). No other treatment group was associated with reduced risk of PFC.
Conclusion: Early anti-TNF therapy prevents perianal fistula development, especially among patients at increased risk.