RESUMO
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.
RESUMO
BACKGROUND: Endoscopic mucosal healing is the current therapeutic target in Crohn's disease. However, transmural healing could lead to better outcomes. AIMS: To assess whether transmural healing or magnetic resonance imaging (MRI) healing are better therapeutic targets than endoscopic mucosal healing to predict long-term improved outcome in Crohn's disease METHODS: From our MRI database, we retrospectively identified all Crohn's disease patients who had MRI and colonoscopy within a 3-month interval (median interval = 17.5 days). Four groups were considered: endoscopic mucosal healing (no ulceration or aphthoid erosion), MRI healing (no MRI signs of inflammation and no complication), transmural healing (combination of endoscopic and MRI healing) or no healing. Outcomes were time to surgery, bowel damage progression, hospitalisation, major outcomes (one of the three previous endpoints) and Crohn's disease-related drug discontinuation. Results were expressed in multivariable analyses adjusted on potential confounders (hazard ratio (HR) [95% confidence interval]). RESULTS: Among 154 patients with Crohn's disease, 51.9% (80/154), 10.4% (16/154), 19.5% (30/154) and 18.2% (28/154) achieved no healing, endoscopic mucosal healing, MRI healing and transmural healing, respectively. Transmural healing (HR = 0.05 [0.00-0.40], P = 0.002) and MRI healing (HR = 0.09 [0.00-0.47], P = 0.005) were associated with lower risk of bowel damage progression than endoscopic mucosal healing. In addition, achieving transmural healing or MRI healing reduced the risk of experiencing major outcomes compared to endoscopic mucosal healing (HR = 0.28 [0.00-0.74], P = 0.01). Patients with transmural healing also had a decreased risk of relapse-related drug discontinuation (HR = 0.35 [0.13-0.95], P = 0.039) compared to those with endoscopic mucosal healing. CONCLUSION: Transmural healing and MRI healing are associated with lower risk of bowel damage progression than endoscopic mucosal healing and could be considered as better therapeutic targets in Crohn's disease.
