Maarten Cozijnsen

41 Chapter 2 Development and validation of the MINI-index N = 24 N = 55 N = 75 N = 24 N = 55 N = 75 N = 24 N = 55 N = 75 Figure 1. CRP (1a), ESR (1b) and fecal calprotectin (1c) across the different severity categories of endoscopic inflammation, as measured by the SESCD in the derivation cohort The final MINI index was constructed based on the final model which eventually achieved the best performance (R 2= 0.78) (Table 2 and Supplementary table 3). The advisory board used the beta scores of the variables as a general guide to assign weights to the items of the MINI index. We then set the threshold of the MINI that corresponds to MH by exploring the best cutoff values on a ROC curve (AUROC to predict MH was excellent 0.92 [95%CI 0.86 – 0.97], p<0.001; rho=0.70). A cutoff <8 best balanced sensitivity (88%) and specificity (85%) for MH; 41 out of 154 patients (27%) had a MINI index score <8. Validation of the MINI index The median MINI index score of the 168 patients from the validation cohorts, was 11.5 (IQR 1 to 17, range -3 to 25), with 103 (61%) having a score <8 points. MH was detected using MINI<8 as a cutoff with 84% sensitivity and 87% specificity, PPV 78% and NPV 90% (AUROC 0.93 [95%CI 0.89 - 0.97], p<0.001; rho=0.82) (Table 3). The implication of PPV 78%, is that 22% of the 65 patients with MINI<8 did not have MH (n=14). However, of those, 12 (86%) had merely mild inflammation (SESCD 3-9) and only 2 (1.2% of the entire cohort) had moderate-to-severe inflammations. A lower cutoff of <6 was more reliable to diagnose MH; 86% of children with that cutoff had a SESCD<3 (48/56). Of the remaining 14% (n=8), 88% (n=7) had merely mild inflammation (SESCD 3-9) and only one child had moderate-to-severe inflammation (SESCD>9). Approaching it from the other side, a MINI≥8 score was highly accurate to diagnose inflammation: 90% of MINI≥8 (93/103) had mucosal inflammation, of whom 59 (63%) with moderate-severe inflammation. The MINI index not only detected MH but also managed to categorize degree of mucosal inflammation. A score of 8-11 reflected mild inflammation and >11 points moderate-to-severe inflammation (Table 3, Figure 2, Figure 3).