Methotrexate emerges as alternative first-line treatment for pulmonary sarcoidosis
While prednisone is the standard first-line treatment for pulmonary sarcoidosis, side effects can diminish quality of life. Researchers report that methotrexate appears to have fewer side effects and is equally effective as a first-line treatment for the condition.
The findings were reported on May 18, 2025 at American Thoracic Society/ATS 2025 International Conference in San Francisco.
“The PREDMETH study shows that methotrexate is as effective as prednisone for pulmonary sarcoidosis as assessed by FVC [forced vital capacity] after 24 weeks of treatment,” the investigators said. “The total number of side effects was comparable; however, in the methotrexate group fewer side effects were ongoing at 24 weeks,” they added.
The investigators enrolled and randomized 138 subjects diagnosed with pulmonary sarcoidosis, none of whom had been treated for the condition. Of the subjects, 73.7% were male and mean age was 46.6 years.
They received treatment with prednisone (n=70) or methotrexate (n=68). The primary endpoint was change in FVC% at 24 weeks.
At 24 weeks, there was no significant difference in between group change in percentage-predicted FVC.
The total number of adverse events recorded in the study did not differ significantly between the groups. Notably, after 24 weeks fewer adverse events were ongoing in the methotrexate group compared to prednisone (104 versus 171).
Adverse events were different between the groups, with weight gain, insomnia, and increased appetite being most common in the prednisone group, and nausea, fatigue, and liver function abnormalities common in the methotrexate group.
“Results were in line with what we hypothesized,” last-author Marlies Wijsenbeek, MD, a pulmonologist at the Erasmus Medical Center in Rotterdam, Netherlands said. “It was, however, surprising to see that some symptom scores already improved after four weeks of treatment in the methotrexate group.”
The authors concluded, “This study shows for the first time that methotrexate may be a good alternative for prednisone as first-line treatment. Difference in AE profiles provide important grounds for shared therapeutic decision making of patients and doctors.”
