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DEVELOPMENT AND EVALUATION OF A PEDIATRIC UC ACTIVITY INDEX (PUCAI) - A PROSPECTIVE MULTICENTER STUDY

D Turner, AR Otley, D Mack, AH Steinhart, K Uusoue, T Walters, M Zachos, P Mamula, J Hyams, AM Griffiths
The Hospital for Sick Children, Toronto, Ontario, as coordinating site

BACKGROUND: Repeated colonoscopy is the gold standard to assess disease activity in adult ulcerative colitis (UC), but this is not as feasible in children.
AIM: To develop, validate and evaluate a non-invasive index of UC activity for use in pediatric clinical trials.
METHODS: A judgmental approach was used for item generation using a Delphi group of 48 experts in pediatric IBD. Weighting of the items was performed by regression analysis using a prospective cohort of 157 pediatric UC patients from 5 IBD centers. Physician global assessment of disease activity (PGA) was used as the dependent variable and the PUCAI items as the predictors. The beta estimates of the model served to guide the weighting, aided by a correlation matrix. Validation of the weighted PUCAI was performed on a separate prospective cohort of 48 UC children undergoing full colonoscopy. Colonoscopic appearance (Beattie's score), the invasive adult Mayo Clinic score and PGA served as the validation constructs. Reliability was assessed by Intra-class Correlation Coefficient (ICC) using two way random ANOVA. Test-retest reliability was established on 29 patients with unchanged disease activity at a repeated visit. Responsiveness was evaluated at a follow-up visit of 41 active children using effect size statistics and diagnostic utility approaches.
RESULTS: A list of 41 items was generated by the expert panel. Rank order was considered in item reduction, following 4 rounds of feedback to the group. Gradations for the 11 highest ranking items were selected by consensus. The draft PUCAI was completed independently by two physicians on the weighting cohort (n=157, age 12.7±3.8 yr; 77% extensive; 34% moderate to severe, 19% mild). ROC curves confirmed the validity of the gradations. Six items were significant in the regression analysis: stool number, consistency and blood content, abdominal pain, activity level and nocturnal diarrhea. In the validation cohort, the weighted index was highly correlated with PGA (r=0.91, p<0.001), Mayo-Clinic score (r=0.95, p<0.001) and colonoscopic appearance (r=0.76, p<0.001). Correlation was higher than two non-invasive adult indices, calculated simultaneously (Lichtiger (r=0.71) and Seo index (r=0.69)). The laboratory items did not improve the PUCAI performance and thus were removed. Inter-observer and test-retest reliability were excellent (ICC=0.95; 95%CI 0.93-0.97). Cutoff points were established using ROC curves on the full cohort. Excellent responsiveness was found at repeated visits (SRM=2.2, SES=1.9, AUC of ROC=0.97).
CONCLUSION: The rigorously developed PUCAI is a non-invasive, valid, reliable and responsive index to assess disease activity in pediatric UC.

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