Prolonged duration of response to infliximab in early but not late pediatric Crohn's disease

OBJECTIVES: Tumor necrosis factor-a plays a central role in chronic intesti nal inflammation of Crohn's disease. Targeting this cytokine with the chime ric monoclonal antibody infliximab has emerged as an effective form of ther apy in adult Crohn's disease patients. We sought to determine whether infli ximab treatment would benefit pediatric patients with medically refractory Crohn's disease. We also assessed the duration of response, comparing child ren with early disease to children with long-standing (late) Crohn's diseas e. METHODS: Fifteen consecutive children (mean age 12.8 +/- 3.2 yr) with medic ally refractory Crohn's disease were enrolled in a prospective, open-label trial of a single, 5-mg/kg infliximab intravenous infusion. Medically refra ctory disease was defined as an inability to taper steroids, lack of respon se to immunomodulator therapy over 4 months, and active disease as measured by the Pediatric Crohn's Disease Activity Index (PCDAI). Primary endpoints included measurements of disease activity (PCDAI), steroid use, and durati on of clinical response. RESULTS: In all, 14/15 children (94%) improved after infliximab infusion, w ith a significant decrease of both PCDAI and daily steroid use by 4 wk. Ten patients (67%) achieved complete remission by 10 wk. Among the 14 patients who responded, three of six children (50%) with early disease maintained c linical response through the 12-month trial period, compared to none of eig ht children with late disease. There were no serious complications associat ed with the use of infliximab in any of the patients. CONCLUSIONS: Infliximab is safe and effective in the shortterm treatment of medically refractory pediatric Crohn's disease. More importantly, there is a remarkably prolonged duration of response after infliximab therapy in ch ildren with early compared to late Crohn's disease. (C) 2000 by Am. Cell. o f Gastroenterology).