Article Text

Download PDFPDF

  1. E. Helene Ibfelt1,
  2. R. Kart Jacobsen2,
  3. T. I. Kopp3,
  4. R. Cordtz4,
  5. A. Svarre Jakobsen5,
  6. N. Seersholm6,
  7. S. Burhan Shaker6,
  8. L. Dreyer4,7
  1. 1Steno Diabetes Center, Gentofte, Denmark
  2. 2Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark
  3. 3Rigshospitalet, Copenhagen, Denmark
  4. 4Aalborg University Hospital, Aalborg, Denmark
  5. 5Furesø Reumatologerne, Farum, Denmark
  6. 6Herlev and Gentofte University Hospital, Hellerup, Denmark
  7. 7DANBIO Registry, Denmark, Denmark


Background: Methotrexate (MTX) is the recommended first-line drug in EULAR and ACR treatment guidelines for rheumatoid arthritis (RA) and hence the most commonly prescribed DMARD in the treatment of this group of patients. However, lung disease is considered a potential adverse effect of MTX treatment.

Objectives: To investigate the risk of interstitial lung disease (ILD) and acute and chronic respiratory failure in RA patients treated with MTX and other medications.

Methods: From the Danish National Patient Register (DNPR) and the clinical DANBIO Register for rheumatic diseases, we retrieved data on RA patients registered between 1997 and 2015. Information on ILD and respiratory failure outcomes was obtained from DNPR, and information on redeemed prescriptions for MTX and other medications was obtained through linkage to the Danish Prescription Register. Associations between MTX and lung disease outcomes were analyzed in Cox regression models adjusted for age, calendar time, sex and use of other medications possessing the potential for pulmonary toxicity. Standardized Incidence Ratios (SIRs) of lung disease were calculated to compare RA patients to the general population.

Results: Of the 30,512 RA patients identified, 60% patients had redeemed at least one prescription for MTX, 35% had redeemed a prescription for sulphasalazine, 6% had redeemed a prescription of either amiodarone or nitrofurantoin, and 27% had not received any of the included drugs at the end of the 5-year follow-up for ILD and respiratory failure. MTX treatment was not associated with an increased risk of lung disease (≥1 redeemed prescription(s) compared to no prescriptions), HR 1.00 (95% CI 0.78 to 1.27) for ILD and 0.54 (95%CI 0.43 to 0.67) for respiratory failure at 5-year follow-up (Table). The SIR was 3-4 times increased for ILD in MTX-treated RA patients, but this was no different from the RA population in general compared to the background population.


Hazard ratios (HR) with 95% confidence intervals (95%CI) for the risk of interstitial lung disease (ILD) and acute or chronic respiratory failure in 30,512 patients with rheumatoid arthritis up to 5 years after diagnosis.

Conclusion: RA patients had an increased risk of ILD compared to the general population, but that risk was not further increased in patients treated with MTX compared to non-MTX treated.

Disclosure of Interests: None declared

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.