Maarten Cozijnsen

36 Methods The MINI index was derived and then validated on data from four independent prospective cohorts of children with CD, utilizing a blended mathematical–judgmental clinimetric approach. Derivation cohort The derivation of the MINI index utilized data from the ImageKids study: a multicenter, prospective cohort (22 medical centers in 9 countries) aimed to develop and validate magnetic resonance enterography (MRE)-based indices of inflammation and intestinal damage (ClinicalTrials.gov: NCT01881490). A total of 240 children with an established diagnosis of CD were enrolled at the time of performing ileocolonoscopy and MRE at disease onset or thereafter. Explicit demographic and clinical data were recorded, including PCDAI, serum biochemical tests, and stool for FC. Endoscopic disease activity was captured using the SESCD 4 , and mucosal healing was defined as a SESCD<3. MRE assessment of disease severity, performed within 2 weeks of the endoscopy, was captured using overall radiologist assessment (RGA) of bowel inflammation by two independent radiologists, with RGA score<20 mm considered radiographic remission. 20 Deep healing was defined as a combination of RGA<20 mm and SESCD<3. We excluded patients in whom the terminal ileum was not reached during endoscopy, who lacked FC measurement, and patients with isolated L4a or L4b disease as per the Paris classification 21 . A total of 154 children from the ImageKids cohort fulfilled the eligibility criteria and were included in the derivation cohort (Table 1). Validation cohorts The validation of the MINI index utilized three cohorts of children with CD. We applied the same eligibility criteria in the validation cohorts as in the derivation cohort. The first was a prospective cohort assembled at two medical centers in South Korea. Children in clinical remission 1-2 years after diagnosis underwent scheduled ileocolonoscopy or sooner in case of a relapse. The second validation cohort was from a bio-bank registry at Shaare Zedek Medical Center, Jerusalem. All children with CD undergoing ileocolonoscopy at disease onset or thereafter were included, when endoscopic, laboratory and clinical data were prospectively recorded, and stool collected for FC. The third validation cohort was from a clinical trial that randomized 100 children, aged 3-17 years, with new-onset moderate-to- severe CD disease into top-down and step-up treatment groups (TISKids, ClinicalTrials.gov: NCT02517684). 22 We used the ileocolonoscopic, clinical and laboratory data from baseline prior to randomization.