A recent cohort study published in the Journal of American Medical Association provided reassuring findings for dermatomyositis (DM) patients regarding the safety of methotrexate (MTX) usage. DM is a condition characterized by muscle weakness and skin rash, often presents with interstitial lung disease (ILD) as a complication by affecting about 23% of DM patients in North America.
The study was conducted within the NIH- All of Us Research Program to investigate the link between MTX use and ILD development in DM patients. Despite MTX being a first-line treatment for DM, the concerns over its potential pulmonary toxicity have made clinicians to hesitate its use in this patient group.

This research analyzed data from a total of 315 DM patients, of whom 163 met the inclusion criteria. Among them, 58 patients received MTX, while the other 105 did not. The study found that 17% of MTX-exposed patients and 16% of MTX-unexposed patients developed ILD, showing no significant difference in ILD risk associated with MTX use.
The findings contrast with previous studies in populations with rheumatoid arthritis (RA) where MTX has been linked with pneumonitis and pulmonary fibrosis. In the DM group, MTX did not pose a significant risk of ILD development. Also, similar results were observed when analyzing the association between ILD and mycophenolate mofetil/mycophenolic acid (MMF/MPA) which is another commonly used medication for DM.

Rituximab use was also noted in relationship with MTX in this study cohort by possibly indicating established use of these medications together or prescribing patterns based on DM subtype. MTX was negatively associated with malignant neoplasms that suggests potential prescribing patterns or indicates its lower tumorigenicity in this context.
Despite the limitations which include reliance on electronic health records and sample size constraints, these findings offer valuable insights into the safety profile of MTX in DM patients. The outcomes suggest that MTX may not significantly increase the risk of ILD in this population by challenging the previous concerns.
Further prospective studies are imperative to validate the findings of this study and explore potential factors that could influence the observed associations. Overall, this study provides reassuring evidence regarding the use of MTX as a treatment option for DM patients by offering hope for enhanced management strategies in this condition.
Source:
Shah, J. T., Richardson, W. M., Mittal, L., Castillo, R., Mazori, D. R., Caplan, A. S., & Femia, A. N. (2024). Methotrexate Use and Risk of Interstitial Lung Disease in Dermatomyositis. In JAMA Dermatology. American Medical Association (AMA). https://doi.org/10.1001/jamadermatol.2024.0785