title: Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study.
abstract: BACKGROUND
  Methotrexate is the most frequent choice of disease-modifying antirheumatic therapy for rheumatoid arthritis. Although results of studies have shown the efficacy of such drugs, including methotrexate, on rheumatoid arthritis morbidity measures, their effect on mortality in patients with the disease remains unknown. Our aim was to prospectively assess the effect on mortality of methotrexate in a cohort of patients with rheumatoid arthritis.
  
  
  METHODS
  Our cohort included 1240 patients with rheumatoid arthritis seen at the Wichita Arthritis Center, an outpatient rheumatology facility. Patients' details were entered into a computerised database at the time of their first clinic visit. We also obtained and recorded demographic, clinical, laboratory, and self-reported data at each follow-up visit (average interval 3.5 months). We estimated the mortality hazard ratio of methotrexate with a marginal structural Cox proportional hazards model.
  
  
  RESULTS
  191 individuals died during follow-up. Patients who began treatment with methotrexate (n=588) had worse prognostic factors for mortality. After adjustment for this confounding by indication, the mortality hazard ratio for methotrexate use compared with no methotrexate use was 0.4 (95% CI 0.2-0.8). Other conventional disease-modifying antirheumatic drugs did not have a significant effect on mortality. The hazard ratio of methotrexate use for cardiovascular death was 0.3 (0.2-0.7), whereas that for non-cardiovascular deaths was 0.6 (0.2-1.2).
  
  
  CONCLUSIONS
  Our data indicate that methotrexate may provide a substantial survival benefit, largely by reducing cardiovascular mortality. This survival benefit of methotrexate would set a standard against which new disease-modifying antirheumatic drugs could be compared.
authors.affiliation: Arthritis Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Hyon K
authors.initials: HK
authors.lastname: Choi
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Hernán
authors.forename: John D
authors.initials: JD
authors.lastname: Seeger
authors.forename: James M
authors.initials: JM
authors.lastname: Robins
authors.forename: Frederick
authors.initials: F
authors.lastname: Wolfe
mesh_terms: D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000401:mortality; D015897:Comorbidity; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate