“This new safety information is based on FDA’s completed analysis of TNF blockers and reports of lymphoma and other cancers in children and adolescents, a second analysis of TNF blockers and post-marketing leukemia reports in all patients, as well as a post-marketing evaluation of new-onset psoriasis in patients treated with these drugs.”—The US FDA
In addition to the updated Boxed Warning, FDA is requiring companies to: update the Warnings section describing reported cases of leukemia in adults, adolescents, and children to include additional information on malignancies in children and adolescents update the Adverse Events section to include information on reported cases of new-onset psoriasis, and revise the Medication Guide to reflect this new safety information.According to a statement from the agency, “This new safety information is based on FDA’s completed analysis of TNF blockers and reports of lymphoma and other cancers in children and adolescents, a second analysis of TNF blockers and post-marketing leukemia reports in all patients, as well as a post-marketing evaluation of new-onset psoriasis in patients treated with these drugs.”
FDA suggests that health care professionals discuss with patients and families the increased risk of cancer in children and adolescents treated with TNF blockers, but also take into account the efficacy of the drugs and the risks and benefits of other immunosuppressive regimens, as well as of untreated illness. Clinicians are also advised to continue monitoring for emergence of malignancies and emergence or worsening of psoriasis (particularly pustular and palmoplantar forms), and to inform patients, their families, and caregivers of the signs and symptoms of malignancies or psoriasis so they are aware of and able to notify their health care professional of any unusual signs or symptoms.
Pediatric warning based on 48 cases, 11 deaths
The warning on pediatric malignancies was based on 48 cases of malignancies in children and adolescents, about half of which were lymphomas. Typically rare malignancies such as leiomyosarcoma, hepatic malignancies, and renal cell carcinoma, were also reported.
There were 11 deaths, caused by hepatosplenic T-cell lymphoma (9 cases), T-cell lymphoma (1 case), and sepsis after remission of lymphoma (1 case).
Malignancy rates were consistently higher than expected with Remicade for lymphomas and for all malignancies, and were higher than background with Enbrel for lymphomas but not for all malignancies. Humira and Cimizia malignancy rates were not calculated because they are seldom used in pediatric patients, and Simponi was not included because it had not been approved at the time of the analysis.
The FDA concluded that there is an increased risk of malignancy with TNF blockers but that this risk cannot be “fully characterized” until additional data become available from ongoing long term, observational, post-marketing studies and registries.
Reference
1. US Food & Drug Administration MedWatch Alert. Tumor Necrosis Factor (TNF) Blockers (marketed as Remicade, Enbrel, Humira, Cimzia, and Simponi) August 2009. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm175843.htm
PubMed: Related Articles