Children using tumor necrosis factor-alpha (TNF) blockers may experience an increase risk of malignancy, according to an investigation conducted by researchers from the FDA.
In the study promoted by reports of malignancies in children using TNF blockers, researchers searched the Adverse Event Reporting System (AERS) database for all claims of malignancy in children using infliximab, etanercept, and adalimumab who initiated therapy between 0 and 18 year old. Included in the 48 cases identified in the database were 31 following infliximab use, 15 following etanercept use, and 2 following adalimumab use. Reporting rates for infliximab and etanercept were compared with the background cancer rate in the general pediatric population. Most of the children evaluated received TNF blocker therapy for a prolonged period, which the study’s authors say suggest the cases were not preexisting malignancies that were misdiagnosed as a rheumatic condition.
The results of the investigation revealed that the reporting rate for US cases of malignancy in children for infliximab was 66 per 100,000 patient years, 4 times the estimated background rate for the general US pediatric population. For lymphomas in children, the reporting rate was 44 per 100,000 patient years, 18 times the background rate.
For etanercept, the reporting rate for US cases of malignancy in children was 22 per 100,000 patient years and approximated the background rate. However, for lymphomas, the reporting rate with etanercept was 11 per 100,000 patient years, 5 times the background rate for lymphomas in children.
In editorial accompanying the report, Thomas Lehman, MD, from the Hospital for Special Surgery and Weill Medical College at Cornell University in New York, pointed out that it is important to recognize that 25 of the 48 of malignancies occurred in children with inflammatory bowel disease who were also receiving immunosuppressants and thus the study findings are not directly relevant to children with juvenile idiopathic arthritis (JIA).
“The risk of malignancy should be considered prior to initiating TNF blockers in children, particularly as some of the reported cases involved types of cancers not commonly seen in children and that are usually associated with immunosuppression,” the study’s team concluded. In addition they suggested that the true incidence rate for the events in the pediatric population may be even higher due to substantial under-reporting to the FDA’s MedWatch program.
This report’s findings are published in Arthritis & Rheumatism (2010 Apr 13. [Epub ahead of print]).