Melanoma associated with tumour necrosis factor-α inhibitors: a Research on Adverse Drug events And Reports (RADAR) project

Background Tumour necrosis factor-alpha inhibitors (TNF alpha Is) are used for treatment of inflammatory disorders. There is evidence linking these agents with occurrence of malignancies. For four out of five TNF alpha Is 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 TNF alpha Is and development of malignant melanoma. Methods We searched the FDA Adverse Event Reporting System (FAERS) database for terms related to melanoma and TNF alpha Is 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 TNF alpha Is vs. nonexposed subjects. Results There were 972 reports of melanoma associated with a TNF alpha I identified in the FAERS database, with 69 reports among individuals using more than one TNF alpha I. A safety signal was detected for infliximab, golimumab, etanercept and adalimumab, but not certolizumab pegol. For TNF alpha Is 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 TNF alpha Is 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 TNF alpha Is 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 TNF alpha I therapy.