US Food and Drug Administration has updated its warning for a group of drugs called TNF blockers, which it says may cause lymphoma and other cancers in children and adolescents. The drugs include Infliximab and Etanercept, which are used for the treatment of juvenile rheumatoid arthritis (JRA), Crohn’s disease and other inflammatory diseases.
The Food and Drug Administration (FDA) is responsible for the regulation of foods, dietary supplements, drugs, vaccines and medical devices, and for ongoing safety monitoring. In June last year the organisation announced that it was investigating the possible association between drugs to block tumour necrosis factor alpha (TNF-alpha), a protein involved in mediating the immune and inflammatory response, and the development of lymphoma (cancer of the lymph system), plus other cancers in children and young people.
Over a 10-year period the FDA received some 30 reports of these types of cancer in young people taking TNF blockers alongside other immune-suppressive medicines to treat JRA, Crohn’s disease or other conditions. They called for manufacturers to submit information on cancers in children also taking these drugs.
When the FDA began its investigation of these reports it stated that the potential benefits of the use of TNF blockers outweigh the potential risks in certain children and young adults. It called for manufacturers to submit reports on any cancer cases, which they included in their investigations.
August 4 2009, the FDA released a follow-up report asking for a change to the labelling of TNF blockers. They concluded that, based on analysis of 48 childhood cancer cases, “there is an increased risk of lymphoma and other cancers associated with the use of these drugs in children and adolescents”. There is also an increased risk of new psoriasis.
Manufacturers now have to add this information to drug literature in the form of a warning on the leaflet inserted into the medicines’ packaging. Patients and professionals are encouraged to report any adverse effects of TNF blockers to the FDA through the MedWatch reporting system that they have implemented.
The FDA reviewed case reports of 48 childhood cancers in young people also taking TNF blockers. Half of these were lymphomas, which included both Hodgkin’s and non-Hodgkin’s lymphoma. Other cancers included leukaemia and melanoma. Some rare cancers, like renal cell carcinoma, liver cancers and leiomyosarcoma (a soft tissue cancer starting in the smooth muscle tissue), were also reported. Unfortunately, 11 of these 48 children died.
In their analysis the FDA concludes that, overall, cases of lymphoma and malignancies in children and young people taking Infliximab were higher than would be expected. Children taking Etanercept had higher than expected rates of lymphomas, but overall rates of cancer were as expected. The TNF blockers Adalimumab and Certolizumab were not included in their analysis because these drugs are not often used in children.
The FDA says that, in the cases of childhood cancer that they investigated, the majority of the patients (88%) were also taking other immunosuppressive medicines such as Azathioprine or Methotrexate, which themselves carry warnings about increased cancer risk. It is, therefore, difficult to determine the possible causes of these cancers, but the role of TNF blockers cannot be excluded.
What are TNF blockers?
TNF blockers work by suppressing the immune system through blocking TNF, a substance that causes inflammation, which may lead to bone and tissue damage. This action makes them helpful for treating immune-related disease. The prescribing guidelines for the four TNF blockers that are currently available in the USA (Remicade, Enbrel, Humira and Cimzia) already contains a warning about the possible risk of cancer.
The FDA reports that manufacturers of these drugs are required to report any cases of cancer in children using these medications, so that the FDA can monitor the situation. In addition, the manufacturer of Cimzia will conduct a 10-year study starting in 2009 that will assess the impact of the drug, with particular reference to new cancers.
August 7 2009
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