Development and validation of a score to assess transmural healing and response in patients with Crohn’s disease

Background and Aims As transmural healing (TH) could be the best therapeutic target in Crohn's disease (CD), we aimed to build and validate a score to assess TH and transmural response (TR), and to confirm their association with favorable CD outcomes. Methods DEVISE-CD project encompassed two retrospective cohorts (274 and 224 CD patients for development and validation phase, retrospectively) and one multicenter prospective validation cohort (N=46 patients). A step-by-step process was used to build the modified Clermont score (C-score). The primary endpoints were time to bowel damage progression, and steroid-free clinical remission with fecal calprotectin < 250 (CFREM) at one year for retrospective and prospective validation cohorts, respectively. Results Edema, ulcer, contrast enhancement, diffusion-weighted hyperintensity, fat wrapping, bowel thickening (>3 mm), and enlarged lymph nodes were associated to higher risk of bowel damage progression (p<0.01). Edema, diffusion-weighted hyperintensity, post-gadolinium contrast enhancement, and bowel thickening were highly coexistent (>95%) and collinear (p<0.0001). Bowel thickness had the highest sensitivity to change after treatment (SMD=0.30±1.0)(p=0.001). C-score was calculated as 0.2x(bowel thickness–3mm) + 1.5x enlarged lymph nodes + 2x ulcer. TH (C-score<0.5) (HR=0.28[0.13-0.63],p=0.002; aHR=0.15[0.04-0.53], p=0.003), TR50 (50%-decrease of C-score)(HR=0.30[0.15-0.63], p=0.001; aHR = 0.36[0.14-0.88], p=0.025) or TR25(25%-decrease of C-score)(HR=0.37[0.19-0.71], p=0.003; aHR=0.46[0.23-0.94], p=0.034) prevented bowel damage progression in development and validation cohorts, respectively. In the prospective validation cohort, achieving TH (OR=4.6[1.3–15.6], p=0.016), TR50 (OR=6.9[1.8–26.0], p=0.008) or TR25 (OR=6.0[1.6–22.3], p=0.008) after 12 weeks of anti-TNF therapy led to higher rate of CFREM at one year. Conclusion C-score is a validated, reliable and easy-to-use tool to assess TH and TR in CD patients.