Early Communication About an Ongoing Safety Review of Tumor Necrosis Factor (TNF) Blockers (marketed as Remicade, Enbrel, Humira, and Cimzia)
FDA is investigating the possible association between the use of medicines known as tumor necrosis factor (TNF) blockers and the development of lymphoma and other cancers in children and young adults. These individuals were treated with TNF blockers for Juvenile Idiopathic Arthritis (JIA), Crohn's disease or other diseases. JIA is the new name for what was called Juvenile Rheumatoid Arthritis (JRA).
FDA is investigating approximately 30 reports of cancer in children and young adults. These reports were submitted to FDA's Adverse Event Reporting System over a ten-year interval, beginning in 1998 after approval of the first TNF blocker, and extending through April 29, 2008. These reports described cancer occurring in children and young adults who began taking TNF blockers (along with other immuno-suppressive medicines such as methotrexate, azathioprine or 6-mercaptopurine), when they were ages 18 or less, to treat Juvenile Idiopathic Arthritis (JIA), Crohn's disease or other diseases. Approximately half the cancers were lymphomas and included both Hodgkin's and non-Hodgkin's lymphoma. Lymphoma is a cancer of the cells in the immune system. Lymphoma is not a recognized complication of JIA or of Crohn's disease. Other cancers reported included 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. Long-term studies are necessary to provide definitive answers about whether TNF blockers increase the occurrence of cancers in children because cancers may take a long time to develop and may not be detected in short-term studies.
TNF blockers suppress the immune system by blocking the activity of TNF, a substance in the body that can cause inflammation and lead to immune system-related diseases. There are currently four TNF blockers available in the United States. Remicade, Enbrel, Humira, and Cimzia are each approved to treat one or more of a number of immune system diseases including JIA, rheumatoid arthritis, psoriatic arthritis, plaque psoriasis, Crohn's disease, and ankylosing spondylitis. Remicade is approved for use in children to treat Crohn's disease. Enbrel and Humira are approved for use in children to treat JIA.
FDA has been aware of the possible association between the use of TNF blockers and the development of cancer. The prescribing information for all four TNF blockers warns about the possible risk of cancer. FDA is also aware of the risk of hepatosplenic T cell lymphoma in children and young adults with Crohn's disease treated with Remicade and immunosuppressive drugs such as azathioprine or 6-mercaptopurine. This risk was described in the Remicade prescribing information in 2006.
FDA has asked the makers of the TNF blockers approved for use in children (Remicade, Enbrel, and Humira) to provide information about all cases of cancer reported in children taking TNF blockers. The maker of Cimzia is required to conduct a study to assess long-term risks of the product, including lymphoma and other cancers. This study will begin in 2009 and take about 10 years to complete. FDA has contacted medical experts to assess the potential association between TNF blockers and cancers, including lymphoma, and to determine if there are children and young adults with JIA and Crohn's disease who may be at particular risk for developing a lymphoma or other cancer.
This early communication is in keeping with FDA's commitment to inform the public about its ongoing safety reviews of drugs. FDA will communicate the conclusions and any resulting recommendations to the public after it completes its evaluation of the new information within about six months. 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.
The FDA urges both healthcare professionals and patients to report side effects from the use of Remicade, Enbrel, Humira, and Cimzia, to the FDA's MedWatch Adverse Event Reporting program.
by reporting online at www.fda.gov/medwatch/report.htm;
by returning the postage-paid FDA form 3500 available in PDF format at www.fda.gov/medwatch/getforms.htm to 5600 Fishers Lane, Rockville, MD 20852-9787;
by faxing the form to 1-800-FDA-0178; or
by phone at 1-800-332-1088.