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Methotrexate and lung disease in rheumatoid arthritis: a meta-analysis of randomized controlled trials

Richard Conway1, Candice Low, Robert J Coughlan

  • 1Galway University Hospitals, Merlin Park, Galway, Ireland.

Arthritis & Rheumatology (Hoboken, N.J.)
|April 24, 2014
PubMed
Abstract

Insights

Methotrexate use in rheumatoid arthritis (RA) patients slightly increases the risk of lung disease, particularly respiratory infections and pneumonitis. However, it does not significantly raise the risk of death from lung disease.

Area of Science:

  • Rheumatology
  • Pulmonology
  • Clinical Pharmacology

Background:

  • Methotrexate is a common treatment for rheumatoid arthritis (RA).
  • RA patients face risks of pulmonary manifestations and respiratory infections.
  • Methotrexate itself has been linked to interstitial lung disease.

Purpose of the Study:

  • To evaluate the relative risk (RR) of pulmonary disease in RA patients treated with methotrexate.
  • To assess the association between methotrexate and adverse respiratory events in RA.

Main Methods:

  • Systematic review and meta-analysis of double-blind, randomized controlled trials (RCTs).
  • Searched PubMed and Cochrane databases (1990-2013).
  • Included studies with >=100 subjects and >=24 weeks duration; used Mantel-Haenszel method for RR.

Main Results:

  • 22 studies with 8,584 participants met criteria; low heterogeneity (I²=3%).
  • Methotrexate associated with increased risk of all adverse respiratory events (RR 1.10) and respiratory infection (RR 1.11).
  • No increased risk of lung disease death (RR 1.53) or noninfectious respiratory events (RR 1.02); significant pneumonitis risk (RR 7.81).

Conclusions:

  • Methotrexate shows a small but significant increase in lung disease risk for RA patients.
  • The primary risks identified are respiratory infections and pneumonitis.
  • Methotrexate remains a valuable RA treatment, but pulmonary risks warrant monitoring.

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