TNF blockers, a class of drugs that includes Remicade, Enbrel, Humira, Cimzia and Simponi, will bear stronger warnings about their association with various forms of cancers when they are used to treat children, the Food & Drug Administration (FDA) said yesterday. The drugs already carry a black-box warning that they may cause cancer. But the FDA said yesterday the Boxed Warnings must highlight the drugs’ possible risk of lymphoma and other cancers in children and teens.
The FDA had been studying the link between the pediatric uses of TNF blockers and cancer since 2008. The safety review was prompted by approximately 30 reports of cancer in children and adolescents treated with TNF blockers.
According to a notice posted on the FDA’s Website on yesterday, the agency has identified 48 cases of malignancies in children and adolescents treated with TNF blockers. Approximately half were lymphomas, including Hodgkin’s and non-Hodgkin’s lymphoma. Other malignancies reported include leukemia, melanoma, and solid organ cancers. Malignancies such as leiomyosarcoma, hepatic malignancies, and renal cell carcinoma, which are rare in children, were also reported.
Of the 48 cases of cancer, there were 11 deaths, the FDA said. The causes of death included hepatosplenic T-cell lymphoma (9 cases) and T-cell lymphoma (1 case). In the remaining case, the patient died from sepsis after achieving remission of the lymphoma.
Cimzia, approved in April 2008, and Simponi, approved in April 2009, were not included in the FDA’s review because they are not approved for use in children and were minimally used during the review period.
The FDA is requiring manufacturers of TNF blockers to update the Boxed Warning in the prescribing information to alert healthcare professionals of an increased risk of lymphoma and other malignancies in children and adolescents treated with TNF blockers. Along with updating the drugs’ labels, the FDA is requiring companies to add information about cancer risks to patient medication guides. The FDA said it is also working with the manufacturers to further define the scope of the cancer risk.
In addition to the updated Boxed Warning, the FDA also required several other changes to the prescribing information for TNF blockers to warn of and mitigate the risks associated with these drugs. These changes are based on additional safety reviews and include:
- Update to the Warnings section describing reported cases of leukemia in adults, adolescents, and children. Changes to the Warnings section of the labeling will also include additional information on malignancies in children and adolescents (see also Boxed Warning information above).
- Update to the Adverse Events section to include information on reported cases of new-onset psoriasis.
- Revised Medication Guide to reflect this new safety information.
In children, TNF blockers are used to treat rheumatoid arthritis, inflammatory bowel disorder and Crohn’s disease. They are also approved to treat a variety of chronic, inflammatory and autoimmune system diseases including juvenile idiopathic arthritis, rheumatoid arthritis, psoriatic arthritis, plaque psoriasis and ankylosing spondylitis. TNF blockers work by neutralizing a protein that, when overproduced, causes inflammation and damage to bones, cartilage and other tissue.