Infliximab use in children and adolescents with inflammatory bowel disease

Abstract

Infliximab is a chimeric monoclonal antibody (75% human, 25% murine) against tumor necrosis factor-alpha, a cytokine with a central role in the pathogenesis of inflammatory bowel disease. Large randomized controlled trials have shown the efficacy and safety of infliximab for the induction and maintenance of remission in adult patients with active Crohn disease (CD). In children and adolescents, mostly small, nonrandomized, non-placebo-controlled studies have supported the notion that infliximab is a potent drug in a population that does not respond to standard therapies. The safety of infliximab is of major concern, and the most frequent severe adverse events are related to severe infections and reactivation of tuberculosis. Non-life-threatening infusion reactions occur rather frequently and seem to be related to the formation of antibodies. The indications for infliximab treatment are therapy-resistant luminal CD (no efficacy or insufficient efficacy of conventional treatment) and therapy-resistant fistulas. An efficient remission induction strategy consists of 3 initial infliximab infusions at 0, 2, and 6 weeks in a dosage of 5 mg/kg to sustain remission. Patients needing maintenance therapy are subsequently treated with an infliximab infusion every 8 weeks. There are indications that the early stages of CD may be more susceptible to immunomodulation, and the natural history of CD may be altered by the introduction of infliximab early in the disease process instead of waiting until conventional therapy has failed. Major points of discussion are whether infliximab maintenance treatment should be episodic (on demand) or scheduled and when infliximab therapy can be discontinued.