title: Skin cancer, rheumatoid arthritis, and tumor necrosis factor inhibitors.
abstract: OBJECTIVE
  To determine the rates of reported non-melanoma skin cancer (NMSC) in a large cohort of patients with rheumatoid arthritis (RA) in comparison to patients with osteoarthritis (OA) and to determine risk factors for the development of NMSC in patients with RA.
  
  
  METHODS
  Self-reported information from 15,789 patients with RA and 3,639 patients with OA were collected through semi-annual questionnaires since 1999. Survival analyses were used to determine incidence rates for NMSC among patients with RA and OA. Multivariate Cox proportional hazard models were used to estimate hazard ratios (HR) for the development of NMSC. Separate analyses were performed for patients with RA to explore associations between use of immunosuppressive medication and development of NMSC.
  
  
  RESULTS
  The crude (unadjusted) incidence rate for reported NMSC among patients with RA and OA were 18.1 and 20.4 per 1000 patient years, respectively. OA patients were older, more likely to be Caucasian, and had higher past incidence of NMSC. Age, male sex, Caucasian race, and history of NMSC prior to entry into the database were associated with an increased risk of NMSC in multivariate Cox proportional hazard models. After adjustment for covariates, RA was associated with an increased risk of NMSC (HR 1.19, p = 0.042). Among RA patients, the development of NMSC was associated with use of prednisone (HR 1.28, p = 0.014) and tumor necrosis factor (TNF) inhibitors alone or with concomitant methotrexate (HR 1.24, p = 0.89 and HR 1.97, p = 0.001, respectively) in addition to established risk factors including fair skin, age, male sex, and previous history of NMSC. No association was found between use of methotrexate or leflunomide and development of NMSC (HR 1.12, p = 0.471, HR 0.83, p = 0.173, respectively).
  
  
  CONCLUSIONS
  In this large, national cohort, RA was associated with an increased risk for development of NMSC. Among patients with RA, use of TNF inhibitors and prednisone were associated with an increased risk of NMSC.
authors.affiliation: Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, California, USA.
authors.forename: Eliza F
authors.initials: EF
authors.lastname: Chakravarty
authors.forename: Kaleb
authors.initials: K
authors.lastname: Michaud
authors.forename: Frederick
authors.initials: F
authors.lastname: Wolfe
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology* / Q000276:immunology; D002280:Basal Cell Carcinoma / Q000453:epidemiology / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D016016:Proportional Hazards Models; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D011241:Prednisone; D008727:Methotrexate