Is chronic interstitial lung disease a complication of long-term methotrexate use?-10 year study investigates

Julie K Dawson, Deepti Kapur, Imna Fazel Rahiman


Background: Methotrexate use is known to be associated with acute pneumonitis, an acute hypersensitivity reaction. Historically there have been concerns that methotrexate may be a cause for chronic pulmonary fibrosis. We wanted to study the effect of long-term methotrexate use on the incidence of chronic interstitial lung disease (ILD).


All patients commenced on methotrexate in our unit between 2004 – 2007 were evaluated retrospectively from our Hospital trust records after 10 years of follow up. 

The incidence of pulmonary fibrosis was based on clinical presentation with symptoms of dyspnoea and confirmation by means of pulmonary function tests and detection of pulmonary fibrosis on high resolution computed tomography of the chest  


Data for 129 patients were analysed. 64/ 129 (50 %) patients completed 10 years of methotrexate treatment at follow up. Methotrexate was used for various indications, most commonly rheumatoid arthritis (106).

Four male patients developed chronic ILD. All cases were in patients with Rheumatoid Arthritis and the incidence in Rheumatoid Arthritis subgroup was 4/ 106 (3.8%). 

There was no association of symptomatic ILD to the duration or dose of methotrexate therapy.


All cases of ILD were in male patients with rheumatoid arthritis, they had usual interstitial pneumonia pattern ILD typical of Rheumatoid Arthritis associated ILD and the incidence rate was comparable to previous studies on rheumatoid arthritis associated with interstitial lung disease (4 – 7 %). This adds to previous publications from shorter-term studies showing a lack of evidence that MTX could be causing chronic ILD.


Methotrexate; chronic pulmonary fibrosis; interstitial lung disease; rheumatoid arthritis

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DOI: https://doi.org/10.18282/rcsm.v2.i1.719


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