Proximal Crohn's Disease Location is Associated with a More Benign Course of Perianal Crohn's Disease (the PERIAPROX Study)

Background Proximal Crohn’s disease (CD) location (L4 according to the Montreal Classification) is associated with a more severe course with higher risk of abdominal surgery. However, little is known about the relation with perianal disease. The aim of our study was to investigate the impact of L4 disease location on perianal disease incidence and clinical course. Methods A case-control study was conducted in the prospectively maintained ENEIDA database for all CD with and without L4 location between January 2005 and March 2023. Demographic data, disease characteristics, perianal disease diagnosis and evolution according to biologic therapy and surgery requirement were collected. Demographic data, CD characteristics, perianal disease diagnosis and course were analyzed. Cox proportional hazards and Kaplan-Meier methods were used for the analysis of perianal incidence, and biologic and surgery requirement. Results A cohort of 14022 CD patients were included in the analysis. The mean follow-up duration was 6.4 years (SD 4.9). L4 location showed a lower prevalence of perianal disease (18.0 vs 19.9%, p=0.018), with lower rate of fistulas (60.9 vs 66.1%, p=0.021) and perianal abscesses (33.5 vs 39.4%, p=0.013). Perianal disease and L4 were associated with male sex (OR 1.29, p<0.001), younger age (43 vs 44), and the structuring phenotype (OR 2.14, p<0.001). L4 location was associated with a lower incidence of perianal disease (HR 0.891, p=0.041), while proctitis was associated with a higher risk (HR=2.161, p<0.001). L4 location was also associated with a lower requirement for biologics (HR 0.712, p=0.023), along with advanced age (HR 0.988, p<0.001). Proctitis (HR 1.292) and a history of perianal surgery (3.373) were associated with a higher requirement for biologics. At univariate analysis, L4 location was associated with a lower requirement of surgery (HR 0.833), however at multivariate analysis this finding was not confirmed (p=0.525). Instead, a history of active smoking (HR 1.419), the use of biologics (HR 2.262), and CD penetrating pattern (HR 1.277) were associated with a higher requirement for perianal surgery. Conclusion L4 location is associated with a lower incidence of perianal disease and a more benign course with lower requirement for biologics and surgery.