Controlled Ileal Release Budesonide in Pediatric Crohn Disease: Efficacy and Effect on Growth

BACKGROUND: Although the effectiveness of controlled ileal release (CIR) budesonide in children can be extrapolated from adult studies, there are currently no data available concerning the effects of CIR budesonide therapy on linear growth. In the absence of controlled, prospective pediatric clinical trials, we reviewed the outcomes, particularly linear growth, of children and adolescents given CIR budesonide to treat active intestinal inflammation and to maintain remission. METHODS: Thirty-two children (20 males) aged 14.1 +/- 2.7 years with Crohn disease of the distal ileum with or without right colon involvement were treated for active Crohn disease (baseline Pediatric Crohn Disease Activity Index, 34 +/- 14) with 9 mg daily of CIR budesonide through the Hospital for Sick Children, University of Toronto, Inflammatory Bowel Diseases program. RESULTS: At first follow-up visit 8.7 +/- 6.0 weeks later, 19 of 32 (59%) were judged by the physician to have responded. In the subset of 22 patients who had laboratory tests repeated at the first follow-up visit, their Pediatric Crohn Disease Activity Index fell from 33 +/- 14 to 22 +/- 16 (P = 0.001). The Pediatric Crohn Disease Activity Index score fell to less than 15 (cut-off score remission) in 29%. Six prepubertal responders continued to receive 6 mg CIR budesonide for 6 to 13 months. Five of the 6 experienced only mild or no gastrointestinal symptoms and gained weight. Nevertheless, their mean height velocity was only 2.3 +/- 1.0 cm/year, and none grew at a rate of more than 4cm/year whilst receiving CIR budesonide. CONCLUSIONS: These data provide grade III evidence of modest effectiveness of CIR budesonide in children with active Crohn disease confined to the ileum with or without right colon involvement. The subnormal growth observed with continued therapy is concerning and may reflect either inadequately controlled intestinal inflammation or direct suppression of linear growth, as is observed with conventional corticosteroids. Randomized controlled pediatric trials of CIR budesonide must include parameters of linear growth as an outcome variable.