Methotrexate Matches Prednisone in Pulmonary Sarcoidosis Treatment Efficacy: Study

A new randomized trial, PREDMETH, has found that methotrexate is as effective as prednisone in improving lung function in treatment-naive patients with pulmonary sarcoidosis, and may offer a more tolerable side effect profile. Prednisone remains the first-line treatment, but its long-term side effects-such as weight gain, insomnia, and cushingoid appearance—often impact patient quality of life. Methotrexate, a potential alternative, had not previously been tested as a first-line option.

The PREDMETH trial, conducted across 17 hospitals in the Netherlands, randomized 138 patients (70 to prednisone, 68 to methotrexate) and assessed treatment over 24 weeks. The main outcome was change in forced vital capacity (FVC%), a key measure of lung function. Results showed no significant difference in FVC% change between the two groups at 24 weeks.

The adjusted between-group difference was -1.8% (90% CI -4.40 to 0.76), meeting the threshold for non-inferiority. Medication adherence was high in both arms—83% in the prednisone group, 81% in the methotrexate group. While the total number of adverse events (AEs) was similar across both groups, fewer AEs were still ongoing at 24 weeks in the methotrexate group (104 vs 171). Prednisone’s common side effects included increased weight, appetite, insomnia, and steroid-related appearance changes.

Methotrexate was associated more with nausea, fatigue, mild liver changes, and infections. This is the first trial to show that methotrexate may be a viable first-line option for pulmonary sarcoidosis. The distinct AE profiles highlight the importance of involving patients in choosing between therapies based on tolerance and lifestyle impact.