title: Melanoma associated with tumour necrosis factor-α inhibitors: a Research on Adverse Drug events And Reports (RADAR) project.
abstract: 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'.
  
  
  OBJECTIVE
  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.
authors: Department of Dermatology, Northwestern University, 676 N. Saint Clair Street, Suite 1600, Chicago, IL, 60611, U.S.A.
authors: B
authors: B
authors: Nardone
authors: J A
authors: JA
authors: Hammel
authors: D W
authors: DW
authors: Raisch
authors: L L
authors: LL
authors: Weaver
authors: D
authors: D
authors: Schneider
authors: D P
authors: DP
authors: West
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D006801:Humans; D008545:Melanoma / Q000139:chemically induced*; D012307:Risk Factors; D012878:Skin Neoplasms / Q000139:chemically induced*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D014409:Tumor Necrosis Factor-alpha