Objectives: Tumor necrosis factor-alpha plays a central role in chronic intestinal inflammation of Crohn's disease. Targeting this cytokine with the chimeric monoclonal antibody infliximab has emerged as an effective form of therapy in adult Crohn's disease patients. We sought to determine whether infliximab treatment would benefit pediatric patients with medically refractory Crohn's disease. We also assessed the duration of response, comparing children with early disease to children with long-standing (late) Crohn's disease.
Methods: Fifteen consecutive children (mean age 12.8 +/- 3.2 yr) with medically refractory Crohn's disease were enrolled in a prospective, open-label trial of a single, 5-mg/kg infliximab intravenous infusion. Medically refractory disease was defined as an inability to taper steroids, lack of response 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 duration of clinical response.
Results: In all, 14/15 children (94%) improved after infliximab infusion, with 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 clinical response through the 12-month trial period, compared to none of eight children with late disease. There were no serious complications associated with the use of infliximab in any of the patients.
Conclusions: Infliximab is safe and effective in the short-term treatment of medically refractory pediatric Crohn's disease. More importantly, there is a remarkably prolonged duration of response after infliximab therapy in children with early compared to late Crohn's disease.