P1057 Early use of tumour necrosis factor antagonist for treatment of paediatric Crohn’s disease decreases perianal fistula development: a post-hoc analysis of a prospective, multicentre study
Authors: Gadepalli S , Adler J ,   BISCUIT study group
Published: January 2025

Abstract

Background
Perianal fistulising complications (PFC) occur in nearly a third of children with Crohn’s disease.1 Tumour necrosis factor antagonist (anti-TNF) treatment is associated with a reduced risk of PFC development, although how early to start anti-TNF therapy remains unclear.2, 3 We sought to determine if starting anti-TNF by 60 days after diagnosis is associated with reduced PFC development in a multicentre cohort of children with newly-diagnosed Crohn’s disease.

Methods
Data from paediatric patients (&lt;21 years) with a new diagnosis of Crohn’s disease were prospectively collected by 7 centres, with additional supplemental record review. We defined early initiation of anti-TNF as started before 60 days from diagnosis and prior to PFC development. The primary outcome was time to PFC development. Bivariate comparisons were made with t-test or chi-square. Time to PFC was evaluated with Cox proportional hazard models adjusted for age at diagnosis, gender, race, disease phenotype and location.

Results
Of 699 patients (median age 13.1 years, interquartile range 10.9-15.4, 40% female, 85% White), 248 (35%) received early anti-TNF therapy within 60 days of diagnosis. Patients receiving early anti-TNF were older (median 13.4 vs. 12.9 years; p=0.049). Though there were no differences in timing of anti-TNF by gender (p=0.37), or race (p=0.29). Patients with complex phenotype (stricturing and/or penetrating) were more likely to receive early anti-TNF than inflammatory phenotype (52% vs 32%; p&lt;0.001).
Overall, 278 children (40%) developed PFC, including 78 (28%) treated with early anti-TNF, and 200 (49%) not treated with early anti-TNF (Figure 1). In an adjusted Cox proportional hazard model, risk of PFC was 2.5-fold higher if early anti-TNF was not initiated (hazard ratio [HR] 2.50, 95% confidence interval [CI] 1.44-4.34; p=0.001). White patients were at lower risk compared to non-White patients (HR 0.37, 95% CI 0.22-0.65; p&lt;0.001). Patients with complex phenotype had 2-fold greater risk of PFC than those with inflammatory phenotype (HR 2.06, 95% CI 1.13-3.73; p=0.018). Perianal lesions (skin tags and/or fissures) were associated with 2-fold increased risk of PFC (HR 2.15, 95% CI 1.04-4.47). Age at diagnosis (p=0.84), gender (p=0.11), and upper (p=0.74) or lower tract (p=0.55) disease locations were not associated with PFC development.

Conclusion
Early anti-TNF treatment, within 60 days, should be considered to prevent development of PFC in children with Crohn’s disease as delays more than doubled the risk. This is especially important for high-risk patients, including non-White patients, stricturing and penetrating phenotype and those with perianal lesions.

References
1.Adler J, Dong S, Eder SJ, Dombkowski KJ, ImproveCareNow Pediatric IBDLHS. Perianal Crohn Disease in a Large Multicenter Pediatric Collaborative. Journal of pediatric gastroenterology and nutrition. 2017;64:e117-e124
2.Adler J, Lin CC, Gadepalli SK, Dombkowski KJ. Association Between Steroid-Sparing Therapy and the Risk of Perianal Fistulizing Complications Among Young Patients With Crohn Disease. JAMA Netw Open. 2020;3:e207378
3.Singer AAM, Bloom DA, Adler J. Factors Associated With Development of Perianal Fistulas in Pediatric Patients With Crohn’s Disease. Clinical gastroenterology and hepatology. 2021;19:1071-1073.

Figure 1. Cumulative Hazard of Developing Perianal Fistulising Complication