#4-15E. Rethinking Methotrexate in RA-ILD: Safety and Protective Potential (Rheumatology, 2025)

Have you ever hesitated to prescribe methotrexate (MTX) to a rheumatoid arthritis (RA) patient due to historical concerns about pulmonary toxicity and interstitial lung disease (ILD)? In this episode, we explore a systematic review of 16 studies involving over 36,000 RA patients, which evaluates the progression and development of RA-associated ILD with MTX exposure. The study demonstrates that MTX does not increase the risk of ILD onset or progression. The most critical clinical takeaway is the suggestion that MTX may actually exert a protective effect against RA-ILD progression by effectively controlling systemic inflammation. However, when critically appraising this evidence, listeners should be aware that many of the included studies feature retrospective designs; therefore, potential confounding factors, such as treatment selection bias where MTX is preemptively withheld from patients with baseline respiratory issues, are not entirely eliminated. For clinicians, this paper is highly significant because it provides robust evidence supporting active and confident MTX therapy through appropriate patient selection, challenging long-standing fears of pulmonary toxicity and optimizing daily RA management.

Citation: Mahmoud, Ines, Bouden, Selma, et al. MTX use in the treatment of RA-associated-interstitial lung disease: a systematic review. Rheumatology. 2025. DOI: https://doi.org/10.1093/rheumatology/keaf538

Disclaimer: This audio summary is based on personal interpretation and does not guarantee the exact content of the original paper. Please refer to the original article for details.