Patients with early rheumatoid arthritis who smoke are less likely to respond to treatment with methotrexate and tumor necrosis factor inhibitors: observations from the Epidemiological Investigation of Rheumatoid Arthritis and the Swedish Rheumatology Register cohorts

Arthritis Rheum. 2011 Jan;63(1):26-36. doi: 10.1002/art.27758.


Objective: To determine whether cigarette smoking influences the response to treatment in patients with early rheumatoid arthritis (RA).

Methods: We retrieved clinical information about patients entering the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) early RA cohort from 1996 to 2006 (n=1,998) who were also in the Swedish Rheumatology Register (until 2007). Overall, 1,430 of the 1,621 registered patients were followed up from the time of inclusion in the EIRA cohort. Of these, 873 started methotrexate (MTX) monotherapy at inclusion, and 535 later started treatment with a tumor necrosis factor (TNF) inhibitor as the first biologic agent. The primary outcome was a good response according to the European League Against Rheumatism criteria at the 3-month visit. The influence of cigarette smoking (current or past) on the response to therapy was evaluated by logistic regression, with never smokers as the referent group.

Results: Compared with never smokers, current smokers were less likely to achieve a good response at 3 months following the start of MTX (27% versus 36%; P=0.05) and at 3 months following the start of TNF inhibitors (29% versus 43%; P=0.03). In multivariate analyses in which clinical, serologic, and genetic factors were considered, the inverse associations between current smoking and good response remained (adjusted odds ratio [OR] for MTX response 0.60 [95% CI 0.39-0.94]; adjusted OR for TNF inhibitor response 0.52 [95% CI 0.29-0.96]). The lower likelihood of a good response remained at later followup visits. Evaluating remission or joint counts yielded similar findings. Past smoking did not affect the chance of response to MTX or TNF inhibitors. Evaluating the overall cohort, which reflects all treatments used, current smoking was similarly associated with a lower chance of a good response (adjusted ORs for the 3-month, 6-month, 1-year, and 5-year visits 0.61, 0.65, 0.78, 0.66, and 0.61, respectively).

Conclusion: Among patients with early RA, current cigarette smokers are less likely to respond to MTX and TNF inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / therapy*
  • Combined Modality Therapy
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Logistic Models
  • Male
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Registries
  • Severity of Illness Index
  • Smoking*
  • Sweden
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / immunology


  • Antibodies, Monoclonal
  • Tumor Necrosis Factor-alpha
  • Methotrexate