No Link Found Between Methotrexate and Increased Risk of Interstitial Lung Disease in Dermatomyositis

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An analysis of the NIH's All of Us program finds no increased ILD risk with methotrexate in dermatomyositis.

Results of a new study challenge previous reports of increased risk of interstitial lung disease (ILD) with use of methotrexate in patients with dermatomyositis.

An analysis of data from the National Institutes of Health (NIH)-sponsored All of Us research program, results indicate there were no significant differences in associations with ILD among patients with dermatomyositis present between methotrexate use and elevated risk of ILD have no significant differences in ILD risk with methotrexate exposure.1

“Methotrexate was not associated with increase ILD risk, contrasting with studies in populations with [rheumatoid arthritis] and suggesting [methotrexate] does not pose significant pulmonary toxicity risk in [dermatomyositis]. We obtained similar results with MMF/MPA, medications known to stabilize lung function in [dermatomyositis] but with unknown associations with ILD prevention,” wrote investigators.1

An NIH-sponsored program launched in May 2017, the All of Us research program boasts more than 890 participating sites collecting samples and measurements. With more than 700,000 participants, including 545,000 who have completed initial steps of the program, the program was launched with the intent of achieving 6 strategic goals by the end of 2026, with collection and curation of data and specimens listed as the second goal of the program.1,2

Citing an elevated risk of ILD in patients with dermatomyositis, a team led by Alisa Femia, MD, of the Ronald O. Perelman Department of Dermatology at NYU Grossman School of Medicine, sought to determine how methotrexate use might influence risk based on potential for pulmonary toxicity observed in populations with rheumatoid arthritis. With this in mind, investigators designed their study leveraging data obtained from patients enrolled in the program between May 2018 to July 2022.1

Inclusion criteria for the study included having a diagnosis of dermatomyositis after January 01, 2010, and immunomodulating treatment after first dermatomyositis diagnosis, which included azathioprine, intravenous immunoglobulin, methotrexate, mycophenolate mofetil/mycophenolic acid [MMF/ MPA], rituximab, systemic steroids. Patients were excluded if they had an ILD diagnosis before the first dermatomyositis diagnosis.1

In total, 315 patients with dermatomyositis were identified from within the All of Us database. Of these, 163 met inclusion criteria, with 58 reporting using methotrexate and 105 reporting no methotrexate use. Investigators noted demographic and clinical characteristics were similar between groups, except for methotrexate-treated patients being less likely to have a dermatomyositis-related malignant neoplasm and more likely to receive rituximab. Investigators found 17% (n=18) of those receiving methotrexate and 16% of those unexposed to methotrexate reported ILD, which investigators noted is consistent with reported rates among populations with dermatomyositis.1

Results of the investigators’ analyses found no significant differences in ILD risk with methotrexate exposure when assessed using Kaplan-Meier modeling (hazard ratio [HR], 0.79; 95% Confidence Interval [CI], 0.35 to 1.78; P = .56) or multivariable Cox proportional hazards regression modeling adjusted for sex, malignant neoplasm, and rituximab exposure (HR, 0.79; 95% CI, 0.33 to 1.86; P = .59). Investigators pointed out nonsignificant results were obtained using both models when stratifying by MMF/MPA.1

Investigators noted there were multiple limitations within their analysis to consider when interpreting their findings. These limitations included ascertainment of diagnoses and time of diagnoses using electronic health records, sample size, and lack of information related to validated outcomes, clinical features, severity, subtype, and clinician reasoning for treatment choices.1

“Further investigation of whether prescribing patterns, antitumorigenic effects of [methotrexate], or other factors influence this finding is warranted,” investigators wrote.1


  1. Shah JT, Richardson WM, Mittal L, et al. Methotrexate Use and Risk of Interstitial Lung Disease in Dermatomyositis. JAMA Dermatol. Published online May 01, 2024. doi:10.1001/jamadermatol.2024.0785
  2. Data Snapshots. All of Us Research Hub. Accessed April 30, 2024.