ROCKVILLE, Maryland—The US Food and Drug Administration (FDA) has asked the makers of the tumor necrosis factor (TNF) blockers approved for use in children to provide information about all cases of cancer reported in children taking the drugs. These drugs are infliximab (Remicade^®), etanercept (Enbrel^®), and adalimumab (Humira^®).

The agency is also requiring the maker of certolizumab (Cimzia^®) to conduct a study to assess long-term risks of the product, including lymphoma and other cancers. The study will begin in 2009 and take about 10 years to complete. Furthermore, the agency is convening an expert panel to assess the potential association between TNF blockers and cancers, including lymphoma, and to determine if there are children and young adults with juvenile idiopathic arthritis (JIA) and Crohn’s disease who may be at particular risk for developing a lymphoma or other cancer.

The move was sparked by 30 cases of lymphomas and other cancers in young patients who had been treated with TNF inhibitors before age 18. According to a statement from the agency, “These reports were submitted to FDA's Adverse Event Reporting System over a 10-year interval, beginning in 1998 through April 29, 2008. These reports describe cancer occurring in children and young adults who began taking TNF blockers (along with other immunosuppressive medicines such as methotrexate, azathioprine, or 6-mercaptopurine), when they were ages 18 or less, to treat JIA, Crohn’s disease, or other diseases.”

Approximately half of the cancers were lymphomas, including both Hodgkin's and non-Hodgkin's lymphoma. There were also cases of leukemia, melanoma, and solid organ cancers. “While cancers are known to occur in children and young adults, the reports of these events in children and young adults receiving TNF blockers are of concern and deserve further investigation,” the FDA said.

The statement notes that prescribing information for all four TNF blockers warns about the possible risk of cancer and that the agency is aware of the risk of hepatosplenic T-cell lymphoma in children and young adults with Crohn’s treated with infliximab and immunosuppressive drugs such as azathioprine or 6-mercaptopurine. This risk was described in the Remicade^® prescribing information in 2006.

Translating research into practice

The FDA announcement emphasized that long-term studies are needed to provide definitive answers about the relationship, if any, between TNF blockers and increased risk of cancer in pediatric patients. The agency pointed out that such cancers may take a long time to develop and may not be detected in short-term studies.

The statement concludes, “At the current time, the FDA believes that the potential benefits of the use of TNF blockers outweigh the potential risks in certain children and young adults having one of the diseases for which the TNF blockers are approved to treat. Until the evaluation is completed, healthcare providers, parents, and caregivers should be aware of the possible risk of lymphoma and other cancers in children and young adults when deciding how to best treat these patients.”

Physicians are asked to report side effects from the use of Remicade, Enbrel, Humira, and Cimzia, to the FDA’s MedWatch Adverse Event Reporting program, either by calling 1-800-332-1088; by visting its Webiste at: www.fda.gov/medwatch/report.htm; by printing the postage-paid FDA form 3500 available in PDF format at: www.fda.gov/medwatch/getforms.htm, and returning it to 5600 Fishers Lane, Rockville, MD 20852-9787; or by faxing the form to 1-800-FDA-0178.

Reference

1. FDA. Early communication about an ongoing safety review of tumor necrosis factor (TNF) blockers
(marketed as Remicade, Enbrel, Humira, and Cimzia). FDA Website. http://www.fda.gov/medwatch/safety/2008/safety08.htm#TNF.