In September 2009, Amgen decided to withdraw application for expanded use of its biologic tumor necrosis factor (TNF) blocking agent etanercept (Enbrel) in pediatric patients with moderate-to-severe psoriasis.
Psoriasis affects 2 percent of the U.S. population. The disease is under-recognized in children, although onset is under age 18 in up to one-third of cases.1 Atopic dermatitis is even more common, affecting up to 20 percent of children, with a significant number suffering from severe disease.
We too consider safety the highest priority, but we also recognize that the well-documented - yet underappreciated - risks and life impact of chronic severe inflammatory skin disease warrant systemic treatment. The risks of these diseases should be taken into consideration as much as the theoretical and rare risks of a well-studied drug.
Enbrel is a drug that has been commercially available in the United States for almost 11 years. It initially received Food and Drug Administration (FDA) approval for adults with rheumatoid arthritis. Expanded indication for children with arthritis down to age 4 was granted in May 1999. A total of 440 children have been followed in a prospective juvenile arthritis registry, 33 for more than four years, with no evidence of serious drug-related effects.2
An August 2009 FDA announcement documented 15 (six domestic) cases of malignancy reported to the FDA Adverse Event Reporting System in etanercept-treated children ages birth to 17 years. The six U.S. children, all of whom had rheumatologic disease, were among a group of 9,200 children who received a total of 26,800 etanercept treatment-years between 1998 and 2007.3
While complete epidemiologic data are lacking and there are concerns about underreporting, the rate of development of cancer is influenced by many factors, including underlying disease and other therapies. There is evidence in adults that rheumatoid arthritis and/or psoriasis are independent risk factors for lymphoma, but there is no evidence or theoretical concern that Enbrel carries a greater safety risk for children than adults.
The Amgen-sponsored phase 3 Enbrel pivotal pediatric psoriasis trial demonstrated Level I evidence of safety and efficacy over a 36-week period and was accepted for publication in a top impact-factor journal.4 No other medication used for any pediatric skin disease has been studied so extensively.
The National Psoriasis Foundation ( http://www.psoriasis.org/) can help provide insight into the impact of this decision on patients. In addition to the potentially negative repercussions for our young psoriatic patients, we are concerned that failure to earn pediatric labeling for this well-studied drug has several additional important negative implications:
Currently, the highest level of evidence for treating severe inflammatory skin disease in children supports the use of cyclosporine, azathioprine, mycophenolate mofetil and methotrexate, all systemic immunosuppressive agents that carry significant safety concerns. It is ironic that children are left only with the option of these older drugs, all with a known increased risk of malignancy.
Elaine Siegfried, M.D., is professor of pediatrics and dermatology, Saint Louis University Health Sciences Center, St. Louis, Mo.
1. Trueb RM. Therapies for childhood psoriasis. Curr Probl Dermatol. 2009;38:137-159.
3. Horneff G, De Bock F, Foeldvari I et al. Safety and efficacy of combination of Etanercept and Methotrexate compared to treatment with Etanercept only in patients with juvenile idiopathic arthritis (JIA). Preliminary data from the German JIA Registry. Ann Rheum Dis. 2008.
4. Paller AS, Siegfried EC, Langley RG et al. Etanercept Treatment for Children and Adolescents with Plaque Psoriasis. New Engl J Med. 2008;358:241-251.