Background Several groups have proposed models to predict disease outcomes in pediatric Crohn’s disease (CD), notably the RISK, GROWTH, and the Porto group, but none were externally validated. We aimed to explore these predictive models and individual predictors summarized by the PIBD-ahead project in a prospective inception cohort of pediatric CD. Methods We included children who were diagnosed with CD at two medical centers and followed them at 3 and 12 months thereafter as well as at the last follow-up . Outcomes included steroid-free remission (SFR), surgery and stricturing/fistulizing disease Results 155 children were included (median follow-up of 31 [16–48] months, 107 [71%] had moderate-to-severe disease). Stricturing and penetrating disease at diagnosis were noted in 34 (22%) and two (1.3%) children, respectively, and these were excluded from the relevant analyses. At 1 year, 10 (8.3%) developed new stricturing disease, two (1.7%) developed penetrating disease, seven (5%) required intestinal surgery, and 15 (10%) required perianal surgery. The sensitivity/specificity/PPV/NPV of the GROWTH criteria for predicting SFR at 12 months (occurring in 70% of children) were 20%/85%/76%/31% and for surgery at two years 96%/20%/16%/96%. Strictures were predicted by the RISK model with sensitivity/specificity/PPV/NPV of 33%/73%/18%/86%. The sensitivity/specificity/PPV/NPV of the Porto criteria to predict surgery were 86%/10%/4%/94%. None of the PIBD-ahead predictors were associated with surgery or stricturing disease. Conclusion None of the three main predictive models in pediatric CD achieved sufficient accuracy, far from that reported in the original cohorts. This highlights the necessity of external validation in any prediction model prior to its implementation in clinical practice.

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Background In developing a patient-reported outcome (PRO) for pediatric ulcerative colitis (UC) with guidance from FDA and EMA, 8 items were previously selected based on 79 concept elicitation interviews. An observer RO (ObsRO) was determined to be required for children younger than 8 years. Here, we aimed to finalize the included items and to validate the TUMMY-UC for its psychometric properties. Methods The structure and exact wording of the PRO and the ObsRO versions were determined by cognitive debriefing interviews with children and their caregivers. Weights were assigned to each item based on ranking of importance. Then, in a prospective multicenter study, children with UC between 2–18 years who either underwent colonoscopy or provided stool for calprotectin completed the TUMMY-UC during 4 consecutive days, as well as 7 and 21 days thereafter for evaluating reliability and responsiveness. Construct and discriminative validity were assessed by different measures of disease severity and quality of life (QOL). Results In an iterative process of 129 cognitive interviews, the exact wording of the TUMMY-UC was determined. The PRO and ObsRO were formatted with identical structure to ensure conceptual equivalence for incorporating into one score. 71 children were included in the validation study (39 with colonoscopy and 32 with calprotectin; age 12.3±4.1 years, 26 (36%) in remission, 20 (29%) with moderate-severe disease). There was excellent reliability in the repeated day assessments (ICC 0.93 (0.88–0.96); p<0.001) and after 1 week in those judged as unchanged (0.90 (0.81–0.95); p<0.001). The TUMMY-UC total score had moderate to strong correlations with all constructs of disease severity: r=0.64 with UC Endoscopic Index of Severity (UCEIS, Figure 1), r=0.66 with IMPACT QOL questionnaire, r=0.43 with calprotectin, r=0.82 with the PUCAI, r=0.76 with patient/caregiver global assessment, r=0.5 with CRP, and r=-0.36 with albumin (all p<0.015). There was a slight superiority to combining TUMMY-UC scores of two consecutive days. The index had excellent discrimination of disease activity categories (figure 2) with a score<9 defining remission (Sen=93%, Spec=84%, AUROC=0.95 (95%CI 0.89–0.99). Showing high responsiveness, the DTUMMY-UC differentiated well between children who improved, worsened or remained unchanged after 3 weeks (Figure 3). The best cutoff of the TUMMY-UC to define response was a change of ≥10 points (AUROC 0.93 (95%CI 0.86–0.99)). Conclusion The TUMMY-UC, constructed from a PRO and ObsRO versions for children 8–18 and 2–7 years, respectively, is a reliable, valid and responsive index which can be now used in clinical practice and as an outcome measure in clinical trials.