Methotrexate Effective as Alternative to Prednisone for Pulmonary Sarcoidosis

New findings presented at the 2025 American Thoracic Society (ATS) International Conference suggest that methotrexate may be considered an effective alternative treatment to prednisone for pulmonary sarcoidosis.1,2

Although prednisone is widely considered to be the initial therapy for pulmonary sarcoidosis, its implementation is known to be commonly accompanied by different adverse effects. In the new findings presented at the ATS 2025 International Conference, during a session titled "Advances in the Diagnosis and Management of ILD," the results suggest that methotrexate may serve as an effective alternative, with similar disease control and potentially fewer side effects.

“The results of this trial show that methotrexate can be offered as an alternative for prednisone for patients with pulmonary sarcoidosis,” first author Vivienne Kahlmann, MD, a pulmonologist in training at Erasmus Medical Center in the Netherlands, said in a statement.1

Sarcoidosis is an immune-mediated disorder that is known to be multifaceted, with a highly unpredictable trajectory. Some patients with the condition improve without treatment, whereas others may need immunosuppression to preserve their organ function and to improve their quality of life. Although prednisone is the standard-of-care based on international recommendations, the guidelines were not established via randomized clinical trial data.

Prednisone’s efficacy can have a cost, with undesirable symptoms such as sleep issues, weight gain, and mood shifts having been reported. Its prolonged utilization among patients also potentially raises the risk of long-term complications.

Kahlmann and colleagues’ analysis of methotrexate as an alternative to prednisone was the first randomized controlled trial that made direct comparisons with both of these 2 therapies for pulmonary sarcoidosis. The investigative team involved 17 hospitals in this collaborative study in the Netherlands.

The study was titled PREDMETH, with 137 individuals enrolled as subjects, 69 of whom were treated with prednisone and 68 were given methotrexate.2 Overall, the investigators concluded that methotrexate was shown to be non-inferior to prednisone in the management of pulmonary sarcoidosis over a 24-week period. Methotrexate, on the other hand, was shown by the coauthors to have demonstrated a slower onset but to be ultimately as effective by the 24-week mark.

Kahlmann et al highlighted that while the overall frequency of adverse events was comparable between the 2 cohorts, those in the methotrexate arm of the analysis reported fewer persistent side effects by the study’s conclusion. They noted the differences in both treatments’ side effect profiles: prednisone showed a more common association with insomnia, appetite increases, and weight gain, whereas those in the methotrexate arm more commonly reported fatigue, nausea, and liver enzyme abnormalities.2

“Results were in line with what we hypothesized,” study co-author Marlies Wijsenbeek, MD, a pulmonologist at the Erasmus Medical Center, said in a statement.1 “It was, however, surprising to see that some symptom scores already improved after four weeks of treatment in the methotrexate group.”

Future directions for the investigative team include developing a clinical decision-support tool to aid in the shared decision-making process between clinicians and patients, as well as conducting follow-up analyses. These will include biomarker analyses from blood samples gathered during the course of this analysis to help predict individual treatment responses.

References

1. Newswise. Methotrexate as Effective as Prednisone in Pulmonary Sarcoidosis. American Thoracic Society. May 18, 2025. Accessed May 18, 2025. https://www.newswise.com/articles/methotrexate-as-effective-as-prednisone-in-pulmonary-sarcoidosis.

2. Kahlmann V, Wijsenbeek M, et al. Methotrexate Versus Prednisone as First-line Treatment for Pulmonary Sarcoidosis: The PREDMETH Trial. Abstract presented at the American Thoracic Society (ATS) International Conference 2025 in San Francisco, CA, from May 18 - May 21, 2025.