title: Comparative cancer risk associated with methotrexate, other non-biologic and biologic disease-modifying anti-rheumatic drugs.
abstract: OBJECTIVE
  There is little information comparing the potential risk of cancer across conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). Methotrexate has not been the focus of most contemporary pharmacoepidemiologic studies of cancer.
  
  
  METHODS
  We conducted a comparative effectiveness study with cancer as the outcome. A large observational cohort of RA was followed up from 2001 to 2010. Reports of any cancer prompted a confirmation process that included adjudication of the primary cancer records. We used a propensity score (PS) with relevant covariates and cohort trimming to improve the balance between DMARD cohorts. Cox proportional hazard regression models were constructed to estimate the risk of cancer with various DMARDs, all compared with methotrexate.
  
  
  RESULTS
  We identified 6806 DMARD courses for analysis (1566 methotrexate; 904 nbDMARDs; 3761 TNF antagonists; 408 abatacept; and 167 rituximab). Non-biologic DMARDs (HR 0.17, 95% CI 0.05-0.65) and TNF antagonists (HR 0.29, 95% CI 0.05-0.65) were associated with a reduced adjusted risk of cancer compared with methotrexate. Abatacept (HR 1.55, 95% CI 0.40-5.97) and rituximab (HR 0.42, 95% CI 0.07-2.60) were similar in risk of cancer with methotrexate. These results were robust to sensitivity analyses. After controlling for DMARD exposures, risk factors for cancer included male gender, age, and alcohol consumption.
  
  
  CONCLUSIONS
  Cancer risk was elevated for methotrexate users compared with nbDMARDs and TNF antagonists.
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA; Division of Pharmacoepidemiology, Brigham and Women's Hospital, Boston, MA. Electronic address: dsolomon@partners.org.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Solomon
authors.affiliation: Division of Rheumatology, Albany Medical College, Albany, NY.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Kremer
authors.affiliation: Division of Rheumatology, Massachusetts General Hospital, Boston, MA.
authors.forename: Mark
authors.initials: M
authors.lastname: Fisher
authors.affiliation: Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
authors.affiliation: Clinical Trials Unit, Division of Rheumatology, New York University School of Medicine, New York, NY.
authors.forename: Victoria
authors.initials: V
authors.lastname: Furer
authors.affiliation: Division of Rheumatology, University of Massachusetts Medical School, Worcester, MA.
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Harrold
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine and Division of Gerontology, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD.
authors.forename: Marc C
authors.initials: MC
authors.lastname: Hochberg
authors.affiliation: Department of Biostatistics, University of Massachusetts Medical Center, Worcester, MA.
authors.forename: George
authors.initials: G
authors.lastname: Reed
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA.
authors.forename: Peter
authors.initials: P
authors.lastname: Tsao
authors.affiliation: Clinical Trials Unit, Division of Rheumatology, New York University School of Medicine, New York, NY.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Greenberg
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001688:Biological Products / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced*; D012306:Risk; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D008727:Methotrexate
keywords: Cancer; DMARDs; Epidemiology; Methotrexate; Rheumatoid arthritis