title: The risk of cancer in patients with rheumatoid arthritis taking tumor necrosis factor antagonists: a nationwide cohort study.
abstract: BACKGROUND
  The association between cancer and use of biologic therapy among rheumatoid arthritis (RA) patients remains controversial. We aimed to compare the relative risk of cancer development between RA patients taking tumor necrosis factor α (TNFα) antagonists and those taking nonbiologic disease-modifying anti-rheumatic drugs (nbDMARDs).
  
  
  METHODS
  We conducted a nationwide cohort study between 1997 and 2011 using the Taiwan National Health Insurance Research Database. The risk of newly diagnosed cancer was compared between patients starting TNF-α antagonists (biologics cohort) and matched subjects taking nbDMARDs only (nbDMARDs cohort). Cumulative incidences and hazard ratios (HR) were calculated after adjusting for competing mortality. Standardized incidence ratio (SIR) was calculated for cancer risk. Multivariate analyses were performed using Cox proportional hazards model.
  
  
  RESULTS
  We compared 4426 new users of TNF-α antagonists and 17704 users of nbDMARDs with similar baseline covariate characteristics. The incidence rates of cancer among biologics and nbDMARDs cohorts were 5.35 (95% confidence interval (CI) 4.23 to 6.46) and 7.41 (95% CI 6.75 to 8.07) per 1000 person-years, respectively. On modified Cox proportional hazards analysis, the risk of cancer was significantly reduced in subjects in biologics cohort (adjusted HR 0.63, 95% CI 0.49 to 0.80, P < .001), after adjusting for age, gender, disease duration, major co-morbidities, and prior use of DMARDs and corticosteroids. However, there was an increased risk for hematologic cancers in biologics cohort, yet without statistical significance. The effect of biologics was consistent across all multivariate stratified analyses and the association between biologics use and cancer risk was independent of dosage of concomitant nbDMARDs.
  
  
  CONCLUSIONS
  These findings suggested that RA patients taking TNF-α antagonist are associated with a lower risk of cancer, but not for hematologic cancers, than RA patients taking nbDMARDs alone.
authors.forename: Chun-Ying
authors.initials: CY
authors.lastname: Wu
authors.forename: Der-Yuan
authors.initials: DY
authors.lastname: Chen
authors.forename: Jui-Lung
authors.initials: JL
authors.lastname: Shen
authors.forename: Hsiu J
authors.initials: HJ
authors.lastname: Ho
authors.forename: Chih-Chiang
authors.initials: CC
authors.lastname: Chen
authors.forename: Ken N
authors.initials: KN
authors.lastname: Kuo
authors.forename: Han-Nan
authors.initials: HN
authors.lastname: Liu
authors.forename: Yun-Ting
authors.initials: YT
authors.lastname: Chang
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000208:ethnology; D044466:Asian People / Q000706:statistics & numerical data; D015331:Cohort Studies; D016572:Cyclosporine / Q000627:therapeutic use; D000068800:Etanercept; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000627:therapeutic use; D015994:Incidence; D007341:Insurance / Q000706:statistics & numerical data; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000150:complications / Q000453:epidemiology*; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D006886:Hydroxychloroquine; D016572:Cyclosporine; C529000:golimumab; D000068879:Adalimumab; D000068800:Etanercept; D008727:Methotrexate