Melanoma associated with tumour necrosis factor-α inhibitors: a Research on Adverse Drug events And Reports (RADAR)
B Nardone1, J A Hammel, D W Raisch
1Department of Dermatology, Northwestern University, 676 N. Saint Clair Street, Suite 1600, Chicago, IL, 60611, U.S.A.
Background:
Tumour necrosis factor-α inhibitors (TNFαIs) are used for treatment of inflammatory disorders. There is evidence linking these agents with occurrence of malignancies. For four out of five TNFαIs the Food and Drug Administration (FDA) label states, 'melanoma has been reported in patients treated with these agents'.
Objectives:
To determine whether a statistically significant association exists between administration of TNFαIs and development of malignant melanoma.
Methods:
We searched the FDA Adverse Event Reporting System (FAERS) database for terms related to melanoma and TNFαIs for detection of safety signals. We also searched a large urban academic electronic medical record (EMR) database for which we calculated the relative risk (RR) of melanoma in subjects exposed to TNFαIs vs. nonexposed subjects.
Results:
There were 972 reports of melanoma associated with a TNFαI identified in the FAERS database, with 69 reports among individuals using more than one TNFαI. A safety signal was detected for infliximab, golimumab, etanercept and adalimumab, but not certolizumab pegol. For TNFαIs as a class of drugs, a safety signal was detectable in the FAERS database, and RR was significant in the EMR database. For the EMR cohort, 6045 patients were exposed to TNFαIs and 35 cases of melanoma were detected. Significance for RR was detected for adalimumab (RR 1·8, P = 0·02) and etanercept (RR 2·35, P = 0·0004 < 0·001).
Conclusions:
We identified a significant association between exposure to TNFαIs and malignant melanoma in two different analyses. Our findings add to existing evidence linking these agents with the occurrence of malignant melanoma. Additional investigations are required to explore this association further along with the risk of melanoma with TNFαI therapy.
Insights
Tumour necrosis factor-α inhibitors (TNFαIs) are linked to an increased risk of malignant melanoma. This study found a significant association between TNFαI use and melanoma development in two separate analyses.
Area of Science:
- Immunology
- Dermatology
- Pharmacovigilance
Background:
- Tumour necrosis factor-α inhibitors (TNFαIs) are widely used to treat inflammatory conditions.
- Existing evidence suggests a potential link between TNFαIs and the development of malignancies.
- FDA labels for several TNFαIs include warnings about reported melanoma cases.
Purpose of the Study:
- To investigate a statistically significant association between the use of TNFαIs and the incidence of malignant melanoma.
- To evaluate safety signals for melanoma in relation to TNFαI therapy.
Main Methods:
- Searched the FDA Adverse Event Reporting System (FAERS) for melanoma and TNFαI-related terms.
- Analyzed an electronic medical record (EMR) database to calculate the relative risk (RR) of melanoma in TNFαI-exposed versus non-exposed individuals.
Main Results:
- A safety signal for melanoma was detected in FAERS for infliximab, golimumab, etanercept, and adalimumab.
- The EMR database analysis revealed a significant RR of melanoma associated with TNFαIs as a class.
- Specific significant associations were found for adalimumab (RR 1.8) and etanercept (RR 2.35).
Conclusions:
- A significant association between TNFαI exposure and malignant melanoma was identified through two distinct analytical approaches.
- These findings corroborate existing evidence linking TNFαIs to an increased risk of melanoma.
- Further research is warranted to fully elucidate this association and the melanoma risk associated with TNFαI therapy.
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