Infliximab therapy in pediatric Crohn’s disease: a review

Abstract

Anti-tumor necrosis factor alpha (TNF-α) therapy has re-defined our treatment paradigms in managing patients with Crohn's disease (CD) and ulcerative colitis. Although the ACCENT studies showed proven efficacy in the induction and maintenance of disease remission in adult patients with moderate to severe CD, the pediatric experience was instrumental in bringing forth the notion of "top-down" therapy to improve overall clinical response while reducing the risk of complications resulting from long-standing active disease. Infliximab has proven efficacy in the induction and maintenance of disease remission in children and adolescents with CD. In an open-labeled study of 112 pediatric patients with moderate to severe CD, 58% achieved clinical remission on induction of infliximab (5 mg/kg) therapy. Among those patients who achieved disease remission, 56% maintained disease remission on maintenance (5 mg/kg every 8 weeks) therapy. Longitudinal follow-up studies have also shown that responsiveness to infliximab therapy also correlates well with reduced rates of hospitalization, and surgery for complication of long-standing active disease, including stricture and fistulae formation. Moreover, these children have also been shown to improve overall growth while maintaining an effective disease remission. The pediatric experience has been instructive in suggesting that the early introduction of anti-TNF-α therapy may perhaps alter the natural history of CD in children, an observation that has stimulated a great deal of interest among gastroenterologists who care for adult patients with CD.

Drug Development

“…In pediatric gastroenterology, monoclonal antibodies are used in Crohn disease (CD) based on demonstrated efficacy in induction and maintenance of remission; however, the safety profile is less well established, especially in the longer term. Antitumor necrosis factor (TNF) treatment is associated with a number of serious adverse reactions including infusion reactions, serious infections, tuberculosis reactivation, lymphomas, and other malignancies (12,13). These need careful consideration when making judgments about appropriate ''place in therapy'' for children.…”

Endoscopic and Histological Assessment of Paediatric Inflammatory Bowel Disease Over a 3‐Year Follow‐up Period

“…The progression of both endoscopic and histological disease in relation to treatment is likely to be valuable to better understand the efficacy of treatment, and in particular to assess disease control by observing if mucosal healing is achieved (3,4). The impact of newer therapies on mucosal healing, growth, and relapse rates appear positive but further data are needed in paediatric cohorts (5). There is increasing interest in the differences between endoscopic and histological disease extent (2,6,7).…”