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Data on long-term real-world outcomes of infliximab in pediatric Crohn disease are limited.The aim of the study was to evaluate infliximab optimization and durability in children with Crohn disease.We performed a retrospective review of children with Crohn disease who started infliximab from January 2008 to December 2012 in 4 Canadian tertiary care centers. A priori factors associated with optimization and discontinuation from loss of response were evaluated using logistic regression and Cox proportional hazards model, respectively.One hundred eighty children (54.4% boys) started infliximab; all completed induction. Median age at infliximab start was 14.3 years (Q1, Q3: 12.8, 15.9 years) and median time from diagnosis to infliximab start was 1.5 years (Q1, Q3: 0.6, 3.5 years). At last follow-up, 87.1% were maintained on infliximab (median duration follow-up 85.9 weeks [Q1, Q3: 43.8, 138.8 weeks]). Infliximab optimization occurred in 57.3% (dose escalation 15.2%, interval shortening 3.9%, both 38.2%), primarily due to loss of response. Younger age at diagnosis (<10 years old) and nonstricturing, nonpenetrating behavior were associated with optimization (odds ratio 6.5, 95% confidence interval [CI] 2.0–21.1 and odds ratio 2.1, 95% CI 1.0–4.2, respectively). The 1- and 2-year durability of infliximab (percentage in follow-up who were continuing on infliximab) were 95.5% (95% CI 90.4–98.3) and 91.0% (95% CI 82.4–96.3), respectively. Annual discontinuation due to loss of response occurred at 3.2% per year (95% CI 1.1–5.2).Children with Crohn disease maintain a durable response to infliximab. Optimization occurs frequently and allows for continued use. Younger age at diagnosis and nonstricturing, nonpenetrating behavior are associated with increased need for infliximab optimization.