Development and Validation of a Score to Assess Transmural Healing and Response in Patients With Crohn's Disease.

BACKGROUND & AIMS: Because 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 2 retrospective cohorts (274 and 224 patients with CD for development and validation phase, retrospectively) and 1 multicenter prospective validation cohort (N = 46 patients). A step-by-step process was used to build the modified Clermont score (C-score). The primary end points were time to bowel damage progression, and steroid-free clinical remission with fecal calprotectin <250 at 1 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 < .01). Edema, diffusion-weighted hyperintensity, post-gadolinium contrast enhancement, and bowel thickening were highly coexistent (>95%) and collinear (P < .0001). Bowel thickness had the highest sensitivity to change after treatment (standardized mean difference = 0.30 ± 1.0; P = .001). C-score was calculated as 0.2x(bowel thickness-3mm) + 1.5x enlarged lymph nodes + 2x ulcer. TH (C-score <0.5; hazard ratio [HR], 0.28 [0.13-0.63]; P = .002; adjusted HR [aHR], 0.15 [0.04-0.53]; P = .003), TR50 (50% decrease of C-score; HR, 0.30 [0.15-0.63]; P = .001; aHR, 0.36 [0.14-0.88]; P = .025), or TR25 (25% decrease of C-score; HR, 0.37 [0.19-0.71]; P = .003; aHR, 0.46 [0.23-0.94]; P = .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 = .016), TR50 (OR, 6.9 [1.8-26.0]; P = .008), or TR25 (OR, 6.0 [1.6-22.3]; P = .008) after 12 weeks of anti-tumor necrosis factor therapy led to higher rate of corticosteroid-free remission at 1 year. CONCLUSIONS: C-score is a validated, reliable, and easy-to-use tool to assess TH and TR in patients with CD.

Early Biological Therapy Within 12 Months of Diagnosis Leads to Higher Transmural Healing Rates in Crohn's Disease.

BACKGROUND & AIMS: Transmural healing (TH) is emerging as a potential Crohn's disease (CD) treatment target. Early biological treatment seems to be associated with improved disease outcomes, but its impact on TH remains unclear. We aimed to assess the impact of early biological treatment initiation on TH and its influence on CD prognosis. METHODS: This multicenter retrospective study included adult patients with CD starting biological therapy. TH was assessed using magnetic resonance enterography (MRE) at 12 ± 6 months post-therapy initiation, with radiological examinations reviewed by blinded expert radiologists. TH was defined as complete normalization of all MRE parameters. Timing of biological therapy initiation was analyzed as a continuous variable, with optimal cutoff determined using the Youden index and clinical relevance. Logistic regression with propensity score-adjusted analysis was used to assess the association between early biological therapy initiation and TH. Long-term outcomes (bowel damage progression, CD-related surgery, CD-flare hospitalization, and therapy escalation) were evaluated. RESULTS: Among 154 patients with CD, early biological therapy initiation within 12 months of diagnosis was associated with significantly higher TH rates (adjusted odds ratio [aOR], 3.23; 95% confidence interval [CI], 1.36-7.70; P < .01), which persisted after adjusting for previous biological therapy use (aOR, 2.82; 95% CI, 1.13-7.06; P = .03). Time-to-event analysis demonstrated that TH was significantly associated with reduced risk of bowel damage progression (adjusted hazard ratio [aHR], 0.28; 95% CI, 0.10-0.79; P = .02), CD-related surgery (aHR, 0.21; 95% CI, 0.05-0.88; P = .03) and therapy escalation (aHR, 0.35; 95% CI, 0.14-0.88; P = .02), independently of early biological therapy. CONCLUSIONS: Early initiation of biological therapy within 12 months of diagnosis significantly increases TH rates, leading to improved long-term outcomes in patients with CD.