Factors associated with early outcomes following standardized therapy in children with ulcerative colitis (PROTECT): a multicentre inception cohort study

BACKGROUND: Previous retrospective pediatric ulcerative colitis (UC) studies had limited ability to describe disease progression and identify predictors of treatment response. The PROTECT multicentre inception cohort aimed to identify characteristics associated with outcomes following standardized therapy after initial diagnosis. METHODS: We completed a prospective multicentre inception cohort study at 29 centres in the USA and Canada of paediatric patients aged 4–17 years newly diagnosed with UC who received initial standardized treatment with mesalamine or corticosteroids (CS) guided by the Pediatric UC Activity Index (PUCAI). The key outcomes for this analysis were week 12 CS-free remission, defined as PUCAI<10 and taking only mesalamine, and treatment escalation to anti-TNFα, immunomodulators or colectomy among those initially treated with intravenous (IV) CS. Independent predictors were identified through multivariable logistic regression using a per-protocol approach. Registered with clinicaltrials.gov: NCT01536535 FINDINGS: 428 children initiated mesalamine (n=136), oral CS (n=144), or IV CS (n=148) with initial mean ± standard deviation PUCAI of 31±13, 50±14, and 67±14, respectively (p<0.001). By week 12, CS-free remission taking mesalamine only was achieved by 48% (64/132) initiating with mesalamine, 33% (47/141) with oral CS, and 21% (30/143) with IV CS (p<0.001). Treatment escalation was required in 7% (9/132), 15% (21/141), and 36% (52/143), respectively (p<0.001); 8 patients, all initially treated with IV CS, received colectomy. Predictors of week 12 CS-free remission were baseline PUCAI <35 (odds ratio (OR) 2.4, 95% CI 1.4–4.2; p=0.002), higher baseline albumin by 1 g/dL increments among age < 12 years (4.1, 1.9–8.6; p=0.0003), and week 4 remission (6.3, 3.8–10.4; p<0.0001). Predictors of treatment escalation by week 12 in those initially treated with IV CS included baseline total Mayo score ≥11 (2.6, 0.9–7.2; p=0.068), rectal biopsy eosinophil count ≤32/high power field (4.6, 1.6–12.8; p=0.004), rectal biopsy surface villiform changes (3.1, 1.1–8.6; p=0.034) and not achieving week 4 remission (30.2, 6.4–144.2; p<0.0001). INTERPRETATION: Our findings provide guidelines to assess response of children newly diagnosed with UC to standardized initial therapy and identify predictors of treatment response and failure. These data suggest that additional therapeutic interventions may be warranted to improve early outcomes, especially in those presenting with severe disease and requiring intravenous corticosteroids.