The US FDA has approved Remicade® (infliximab) for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapies such as aminosalicylates, steroids, and immunomodulator drugs (eg, azathioprine and 6-mercaptopurine). As part of the initial approval of Remicade in 1998 for adult patients with moderate to severe Crohn's disease, Centocor Inc committed to study Remicade in children with Crohn's disease.

The first and only biologic treatment for children with active Crohn's disease, Remicade has not been studied in children <6 years of age with the disease. The longer-term (>1 year) safety and effectiveness of Remicade in pediatric Crohn's disease patients has not yet been established in clinical trials.

The safety and efficacy of Remicade were assessed in a randomized, multicenter, open-label study in 112 pediatric patients 6–17 years old with moderately to severely active Crohn's disease and an inadequate response to conventional therapies. All patients were required to be on a stable dose of 6-mercaptopurine, azathioprine, or methotrexate; 35% were also receiving corticosteroids at baseline. All patients received induction dosing of 5 mg/kg Remicade at weeks 0, 2, and 6. At week 10, 103 patients were randomized to a maintenance regimen of 5 mg/kg Remicade given either every 8 weeks or every 12 weeks.

At week 10, 88% of patients were in clinical response (defined as a decrease from baseline in the Pediatric Crohn's Disease Activity Index [PCDAI] score of >e;15 points and total PCDAI score of <e;30 points), and 59% were in clinical remission (defined as PCDAI score of <e;10 points). Approximately 64.5% of patients who were randomized to treatment with Remicade every 8 weeks were in clinical response at 1 year, and approximately 56% of the patients treated with Remicade every 8 weeks were in clinical remission at the end of the 12-month period.

Postmarketing cases of hepatosplenic T-cell lymphoma, a rare but very aggressive and usually fatal type of T-cell lymphoma, have been reported in adolescent and young adult patients with Crohn's disease treated with Remicade concomitant with azathioprine or 6-mercaptopurine therapy. This serious adverse event has been added to the boxed warning in the labeling for the drug.

Remicade was the first biologic treatment approved by the FDA for the treatment of adults with moderate to severe Crohn's disease. Orphan drug designation was granted by the FDA for the treatment of pediatric Crohn's disease in November 2003. In August 2004, the Remicade phase III clinical development program for pediatric Crohn's disease received Fast Track designation by the FDA. In September 2005, Remicade also became the first approved biologic treatment for moderate to severe ulcerative colitis, making it the only biologic indicated for the treatment of both types of inflammatory bowel disease in adults. Remicade is also approved for the treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. More than 700,000 patients have been treated with Remicade worldwide.

A chimeric IgG1κ monoclonal antibody composed of human constant and murine variable regions, Remicade reduces inflammation by neutralizing the biological activity of TNF-alpha. It does this by binding with high affinity to the soluble and transmembrane forms of TNF-alpha, and inhibits binding of TNF-alpha with its receptors. Biological activities attributed to TNF-alpha include induction of pro-inflammatory cytokines such as IL-1 and IL-6; enhancement of leukocyte migration by increasing endothelial layer permeability and expression of adhesion molecules by endothelial cells and leukocytes; activation of neutrophil and eosinophil functional activity; and induction of acute phase reactants and other liver proteins, as well as tissue degrading enzymes produced by synoviocytes and/or chondrocytes. Remicade is the only anti-TNF biologic administered by infusion, and requires as few as six treatments per year.

—A. Techman