P0781 Perianal lesions present at paediatric Crohn’s disease diagnosis require early treatment with tumour necrosis factor antagonist to reduce high risk of perianal fistulising complications: a post-hoc analysis of a prospective, multicentre study
Authors: Adler J , Gadepalli S ,   BISCUIT study group
Published: January 2025

Abstract

Background
Paediatric patients with Crohn’s disease (CD) have differing risks for developing perianal fistulising complications (PFC), which develop in nearly 1 in 3 children with CD.1 Perianal lesions, such as skin tags and/or fissures, at CD diagnosis may augment the risk of PFC development, whereas tumour necrosis factor antagonist (anti-TNF) treatment may reduce the PFC risk.2, 3 We sought to determine the magnitude of PFC risk attributable to perianal lesions, and to evaluate the optimal timing of anti-TNF therapy to prevent PFC in a prospective multicentre cohort of children with CD.

Methods
Data from paediatric patients (&lt;21 yr) with newly diagnosed CD were prospectively collected by 7 centres, with supplemental record review. To evaluate new PFC, we excluded those with PFC within 14 days of CD diagnosis. We defined the timing of anti-TNF after diagnosis but prior to PFC. The primary outcome was PFC development evaluated with Cox proportional hazard models. Bivariate comparisons were made with t-test, chi-square, or Spearman rank sum for age at diagnosis, gender, race, disease phenotype location, and perianal lesions.

Results
Of 546 patients without PFC within 2 weeks of diagnosis (median age 13.1 yr, interquartile range [IQR] 10.9-15.4, 40% female, 85% White),128 (18%) had perianal lesions at diagnosis. In total, 60 patients (11%) had perianal lesions, and 125 (23%) developed PFCs. There were no differences in perianal lesions by age at diagnosis (p=0.34), gender (p= 0.58), race (p=0.15), or phenotype (p=0.16). Median time from CD diagnosis to anti-TNF therapy in those with perianal lesions was 22 days (IQR 13-48), and 60 days (IQR 18-270) for those without perianal lesions (p&lt;0.001).
Perianal lesions at diagnosis were associated with &gt;2-fold increased risk of PFC (hazard ratio 2.39, 95% confidence interval 1.51-3.77). Compared to early anti-TNF and no perianal lesions (reference), those with perianal lesions at diagnosis and anti-TNF delay and had the highest risk of PFC development at nearly every timepoint (Figure 1). Earlier anti-TNF use in those with perianal lesions reduced the risk to near baseline rate of PFC in those without perianal lesions.

Conclusion
Children with CD who have perianal skin tags and/or fissures are at greatly increased risk of developing PFC. Early anti-TNF, ideally starting within 30 days of diagnosis, should be considered to prevent development of PFCs in children with perianal lesions. Delays in anti-TNF treatment in children with perianal lesions can be associated with up to 12-fold greater risk of PFC development by 1 year.

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 by Time to Anti-TNF Start in Patients With and Without Perianal Lesions.