Maarten Cozijnsen

43 Chapter 2 Development and validation of the MINI-index 96% 89% 85% 77% 63% 52% 37% 30% 36% 29% 33% 26% 22% 11% 9% 5% 3% 3% 4% 1% 1% 1% 2% 1% 1% 2% 4% 11% 15% 20% 34% 42% 54% 59% 53% 60% 48% 54% 51% 50% 46% 47% 43% 44% 44% 36% 34% 24% 17% 12% 13% 10% 6% 6% 6% 3% 3% 6% 9% 11% 12% 10% 18% 21% 26% 39% 45% 48% 53% 53% 52% 63% 65% 75% 82% 87% 86% 88% 94%94%94% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% -3 -2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Percentage of patients MINI index score Mucosal healing Mild inflammation Moderate-to-severe inflammation Figure 3. Rates of MH (SESCD<3), mild inflammation (SESCD 3-9) and moderate-to-severe inflammation (SESCD>9) for each MINI index score in all cohorts combined (n=322). Secondary analyses FC alone was slightly less accurate in detecting MH than the MINI index (derivation: AUROC 0.92, rho=0.63. validation: AUROC 0.92, rho=0.73, at an optimal cutoff of <300 μg/g,) (Table 3). Of the 322 children in the entire cohort, 275 (85%) were diagnosed correctly (i.e. either a true positive or true negative test result) by MINI<8 vs. 265 (82%) by FC<300 μg/g (p=0.013). The difference in accuracy between the MINI index and FC was highest among the 76 patients with FC concentrations between 100 and 599 μg/g – a gray range of FC with low discriminatory accuracy. Of these 76 patients, 50 (66%) were diagnosed correctly by MINI<8 and 41 patients (54%) were diagnosed correctly by FC<300 μg/g (p=0.022, number needed to screen 9). PCDAI alone (score <10) had a lower performance (combined data: AUROC 0.81, rho=0.65), as CRP (combined data: AUROC 0.85, rho=0.59) and ESR (combined data: AUROC 0.75, rho=0.46). The accuracy of MINI<8 to detect MH varied slightly between disease location categories of the Paris classification. Sensitivity and specificity were slightly lower in ileal CD (L1), than in colonic and ileocolonic CD (L2/L3) on the combined data (L1: n=77, sensitivity 76%, specificity 77%, AUROC 0.77; L2/L3: n=231, sensitivity 86%, specificity 89%, AUROC 0.87).