Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

No link seen between methotrexate, interstitial lung disease in RA

Key clinical point: Methotrexate therapy does not appear to be a risk factor for interstitial lung disease among patients with RA.

Major finding: Risk of interstitial lung disease was similar for patients filling at least one methotrexate prescription versus none (hazard ratio, 1.00) and lower for those who had ever versus never used the drug (odds ratio, 0.41).

Study details: A Danish nationwide population-based cohort study of 30,512 patients with RA, and a multinational case-control study of 482 RA patients with interstitial lung disease and 741 RA patients without the disease.

Disclosures: The Danish study did not receive any specific funding, and none of its authors reported having any financial disclosures. The multinational study did not receive any specific funding. Dr. Juge disclosed that he had no relevant conflicts of interest, but many of his coauthors reported financial relationships with industry.


Interstitial lung disease (ILD) is a serious and feared complication of RA. As methotrexate can be associated with pulmonary complications including hypersensitivity pneumonitis, the potential risk of developing ILD associated with methotrexate exposure is of great interest to both clinicians and patients. Two abstracts presented at the recent EULAR meeting address this potential increase in risk. One, a multi-national case-control study of 482 RA patients with ILD compared to 741 RA patients without ILD, did not show any increase in risk in RA-associated ILD (RA-ILD) with methotrexate use, though duration of use was not given; in fact, a potential reduction in risk of development of RA-ILD was seen. The other study examined a large national registry of RA patients in Denmark and found an overall increase in risk of ILD in RA patients, but no additional increase in patients treated with methotrexate compared to those who had not received it. Together, these studies are reassuring in that they do not support an increase in risk of development of RA-ILD related to methotrexate use.”

Arundathi Jayatilleke, MD

Lewis Katz School of Medicine, Temple University


Ibfelt EH et al. Ann Rheum Dis. 2020;79[suppl 1]:147-8, Abstract OP0232; Juge PA et al. Ann Rheum Dis. 2020;79[suppl 1]:25, Abstract OP0036.