Investigation of the chronic pulmonary effects of low-dose oral methotrexate in patients with rheumatoid arthritis: a prospective study incorporating HRCT scanning and pulmonary function tests

Rheumatology (Oxford). 2002 Mar;41(3):262-7. doi: 10.1093/rheumatology/41.3.262.


Objective: Methotrexate has a well-recognized side-effect of acute hypersensitivity pneumonitis. There is concern about whether chronic pulmonary toxicity can occur with methotrexate treatment. Our objective was to compare chest high-resolution computed tomography (HRCT) findings and serial pulmonary function tests in rheumatoid arthritis (RA) patients on methotrexate with findings for a control group of patients with RA who were not being treated with methotrexate.

Methods: Study patients had an initial chest radiograph, full pulmonary function tests and chest HRCT. Pulmonary function tests were then performed regularly over a 2-yr period.

Results: Fifty-five RA patients on methotrexate and 73 control patients with RA were enrolled for the study. Mean dose of methotrexate was 10.7 mg/week (S.D. 2.5 mg/week) and mean duration of treatment at entry into the study was 30 (20) months. Twenty per cent of patients with RA treated with methotrexate had pulmonary fibrosis (PF) on initial HRCT compared with 23% in the control group. When the patients with and without PF were compared, there was no statistical difference in the duration (mean difference -4.18 months, P=0.237) or dose (mean difference -0.8 mg/week P=0.52) of methotrexate therapy. Mean changes after 2 yr in forced expiratory volume, forced vital capacity, diffusion capacity for carbon monoxide and residual volumes were not different in the methotrexate group compared with the control group.

Conclusion: There is no evidence to suggest clinically, from HRCT assessment or serial pulmonary function tests, that low-dose methotrexate is associated with chronic interstitial lung disease.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / pathology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Lung Diseases, Interstitial / chemically induced*
  • Lung Diseases, Interstitial / diagnosis
  • Lung Diseases, Interstitial / physiopathology
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Middle Aged
  • Prospective Studies
  • Pulmonary Fibrosis / chemically induced*
  • Pulmonary Fibrosis / diagnosis
  • Pulmonary Fibrosis / physiopathology
  • Radiography, Thoracic
  • Respiratory Function Tests
  • Tomography, X-Ray Computed / methods


  • Antirheumatic Agents
  • Methotrexate