Abstract
BackgroundMalignancy risk may be increased in chronic inflammatory conditions that are mediated by tumor necrosis factor (TNF), such as juvenile idiopathic arthritis (JIA), but the role of TNF in human cancer biology is unclear. In response to a 2011 United States Food & Drug Administration requirement of TNF blocker manufacturers, we evaluated reporting rates of all malignancies in patients ≤30 years old who received the TNF blocker etanercept.MethodsAll malignancies in etanercept-exposed patients aged ≤30 years from the Amgen clinical trial database (CTD) and postmarketing global safety database (PMD) were reviewed. PMD reporting rates were generated using exposure information based on commercial sources. Age-specific incidence rates of malignancy for the general US population were generated from the Surveillance Epidemiology and End Results (SEER) database v7.0.9.ResultsThere were 2 malignancies in the CTD: 1 each in etanercept and placebo/comparator arms (both in patients 18–30 years old). Postmarketing etanercept exposure was 231,404 patient-years (62,379 patient-years in patients 0–17 years; 168,485 patient-years in patients 18–30 years). Reporting rates of malignancy per 100,000 patient-years in the PMD and incidence rates in SEER were 32.0 and 15.9, respectively, for patients 0–17 years and 46.9 and 42.1 for patients 18–30 years old. Reporting rates were higher than SEER incidence rates for Hodgkin lymphoma in the 0-17 years age group. PMD reporting rates per 100,000 patient-years and SEER incidence rates per 100,000 person-years for Hodgkin lymphoma were 9.54 and 0.9, respectively, for patients 0–17 years and 1.8 and 4.2 for patients 18–30 years old. There were ≥5 cases of leukemia, lymphoma, melanoma, thyroid, and cervical cancers. Leukemia, non-Hodgkin lymphoma, melanoma, thyroid cancer, and cervical cancer rates were similar in the PMD and SEER.ConclusionsOverall PMD malignancy reporting rates in etanercept-treated patients 0–17 years appeared higher than incidence rates in SEER, attributable to rates of Hodgkin lymphoma. Comparison to patients with similar burden of disease cannot be made; JIA, particularly very active disease, may be a risk factor for lymphoma. No increased malignancy reporting rate in the PMD relative to SEER was observed in the young-adult age group.
Highlights
Malignancy risk may be increased in chronic inflammatory conditions that are mediated by tumor necrosis factor (TNF), such as juvenile idiopathic arthritis (JIA), but the role of TNF in human cancer biology is unclear
Renal and urinary tract neoplasm were reported in a subject with psoriasis who received placebo and Hodgkin lymphoma was reported in a subject with rheumatoid arthritis (RA) who received etanercept
In summary, overall malignancy reporting rates for pediatric patients receiving etanercept appeared to be higher in the 0–17 years age group compared with incidence rates from a aged pediatric population, but not in young adults aged 18–30 years
Summary
Malignancy risk may be increased in chronic inflammatory conditions that are mediated by tumor necrosis factor (TNF), such as juvenile idiopathic arthritis (JIA), but the role of TNF in human cancer biology is unclear. The role of tumor necrosis factor (TNF) in inflammatory diseases such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and psoriasis is well established, as is the benefit of TNF inhibition in the treatment of these disorders [1]. The role of TNF in human cancer biology is less clear and it has been hypothesized that TNF inhibition may increase the risk of malignancies [3], with prolonged, continuous exposure to TNF blockade [4]. Chronic inflammation and autoimmune properties of these diseases are postulated to contribute to an increased risk of malignancy [11,12]. TNF has been reported to have anticancer properties, it has been suggested that TNF may promote cancer development and progression through cellular transformation, tumor promotion, proliferation, invasion, angiogenesis, and metastasis [13]
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