Tumor necrosis factor alpha blockers and malignancy in children: forty-eight cases reported to the Food and Drug Administration.
OBJECTIVE
Malignancies reported in children using tumor necrosis factor alpha (TNFalpha) blockers have raised concerns of a potential increased risk. This study was undertaken to investigate postmarketing reports of malignancy in children treated with TNF blockers.


METHODS
The FDA's Adverse Event Reporting System was searched to identify malignancies associated with the use of infliximab, etanercept, and adalimumab in children in whom therapy was initiated between the ages of 0 and 18 years. The reporting rates for infliximab and etanercept were compared with the background rate of malignancy in the general pediatric population.


RESULTS
Forty-eight reports of malignancy in children were identified: 31 following infliximab use, 15 following etanercept use, and 2 following adalimumab use. Half of the malignancies reported were lymphomas and included both Hodgkin's and non-Hodgkin's lymphoma. The remaining reported cases involved a variety of different malignancies including leukemia, melanoma, and solid organ cancers. The majority of the reported cases (88%) involved the concomitant use of other immunosuppressants. Reporting rates for malignancy showed that infliximab had a consistently higher reporting rate when compared with background rates in the general pediatric population for lymphomas and all malignancies. The reporting rates for etanercept were elevated above background for lymphomas and were on par with background for all malignancies.


CONCLUSIONS
There is evidence that treatment with TNF blockers in children may increase the risk of malignancy. However, the cases were confounded by the potential risk of malignancy associated with underlying illnesses and the use of concomitant immunosuppressants; therefore, a clear causal relationship could not be established.
Diak
Peter
P
Food and Drug Administration, Silver Spring, MD 20993, USA. peter.diak@fda.hhs.gov
Siegel
Jeffrey
J
La Grenade
Lois
L
Choi
Lauren
L
Lemery
Steven
S
McMahon
Ann
A
D000068879:Adalimumab; D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001171:Arthritis, Juvenile / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects* / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007223:Infant; D000069285:Infliximab; D009369:Neoplasms / Q000209:etiology*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012306:Risk; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept