Early Top-Down Treatment With Biologics Improves the Rates of Transmural Remission in Crohn's Disease-A Risk-Adjusted Propensity Score Matched Analysis

Inflamm Bowel Dis. 2025 Jun 25:izaf112. doi: 10.1093/ibd/izaf112. Online ahead of print.

Abstract

Background: Early top-down treatment with biologics has been associated with higher rates of endoscopic remission compared to step-up treatment in Crohn's disease (CD). The benefits in relation to transmural remission are currently unknown. Better stratification of patients suitable for top-down strategies is needed.

Methods: Retrospective study including CD patients naïve to immunomodulators and biologics and with endoscopic and radiologic evidence of active disease at baseline. Transmural remission rates were compared between patients receiving early top-down treatment (start of biologics within 6 months of immunomodulators) and conventional step-up treatment (start of biologics > 6 months after immunomodulators). The influence of risk factors for disabling disease (age at diagnosis, disease duration, smoking, phenotype, perianal disease, extensive small bowel disease, and elevated C-reactive protein) on transmural remission rates was also assessed and adjusted through propensity score-matched analysis.

Results: In total, 327 patients were included in the main analysis, 47.7% receiving early top-down treatment with biologics. Transmural remission rates decreased from 33.3% to 0% in patients with 0 and 6 risk factors for disabling disease, respectively. Early top-down treatment resulted in higher rates of transmural remission (33.3% vs 18.1%, P = .002) and was an independent predictor for this outcome in the multivariate analysis (odds ratio [OR] 2.187, 95% confidence interval [95% CI], 1.270-3.665, P = .005). Comparable results were found in the propensity score matched analysis (34% vs 17%, P = .002; OR 2.3, 95% CI, 1.268-4.174, P = .006).

Conclusions: Early top-down treatment with biologics improves the rates of transmural remission in CD. Risk factors for disabling disease significantly impact the chances of obtaining transmural remission and may help clinicians identify patients suitable for more aggressive treatment strategies.

Keywords: Crohn's disease; disabling disease; top-down treatment; transmural remission.

Plain language summary

In this study, we demonstrate that a top-down strategy using biologics improves the rates of transmural remission compared to a conventional step-up approach. We also show that risk factors for disabling disease negatively impact the chances of obtaining transmural remission.