Researchers propose suggestions to guide the safer use of methotrexate in RA patients

The use of methotrexate (MTX) as the first-line disease modifying antirheumatic drug (DMARD), either alone or in combination with biologics, helps in decreasing biologic-associated immunogenicity and improve drug survival. However, the role of MTX in hastening the initiation or progression of interstitial lung disease (ILD) is a matter of debate. Now, in the recent issue of Clinical Rheumatology, Metha et al. have put forth certain suggestions, which may help in clinical decision making on the use of MTX in managing RA.

Some of the key suggestions on management approach are the following:

  • An ILD multidisciplinary team comprising of respiratory physicians, rheumatologists and radiologists should discuss the management of RA patients with suspected or established ILD.
  • Assessment of respiratory reserve before the initiation of MTX is recommended in patients with pre-existing lung disease to understand the patient’s potential to cope with event of pneumonitis.
  • A careful risk-benefit analysis based on exercise tolerance, evaluation of symptoms, lung physiology and extent of change in high-resolution CT scanning is necessary prior to MTX initiation in patients with moderate-severe ILD.

More recent clinical evidence refutes the association between MTX and lung disease in RA.  A multivariate analysis carried out by Kiely et al.  has concluded that MTX treatment is not associated with elevated risk for RA-ILD diagnosis and, in contrast, the treatment helps in delaying the onset of ILD. The present study highlighted the need for a concerted effort to terminate the age-old debate and adopt evidence-based prescription approach.


Mehta P, Redhead G, Nair A, Sparks JA, Porter JC. Can we finally exonerate methotrexate as a factor in causing or exacerbating fibrotic interstitial lung disease in patients with rheumatoid arthritis? [published online ahead of print, 2022 Jun 22]. Clin Rheumatol. 2022;10.

Kiely P, Busby AD, Nikiphorou E, et al. Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohorts. BMJ Open. 2019;9(5):e028466.