Interstitial lung disease · Treating pulmonary sarcoidosis
First-Line Treatment of Pulmonary Sarcoidosis with Prednisone or Methotrexate
| Design | Multicentre, open-label, non-inferiority trial |
|---|---|
| Treatment | Methotrexate per a prespecified schedule |
| Control | Prednisone per a prespecified schedule |
| Population | 138 treatment-naive patients with pulmonary sarcoidosis |
| Follow-up | 24 weeks |
| Primary endpoint | Mean change from baseline to week 24 in percentage predicted FVC, non-inferiority margin 5 percentage points |
| Result | FVC rose 6.75 percentage points (95% CI 4.50 to 8.99) with prednisone and 6.11 (3.72 to 8.50) with methotrexate. Adjusted between-group difference -1.17 percentage points (-4.27 to 1.93), meeting non-inferiority. Adverse events were similar in frequency, but weight gain, insomnia and increased appetite dominated the prednisone arm. |
| Secondary endpoints | Adverse events, symptom scores, steroid exposure |
In patients with pulmonary sarcoidosis, initial treatment with methotrexate was noninferior to that with prednisone with regard to the change from baseline to week 24 in the percentage of the predicted FVC. Differences in the side-effect profile between methotrexate and prednisone may inform shared decision making by providers and patients about the appropriate treatment approach.
The trial authors, in the published abstract
The first randomised challenge to prednisone as automatic first-line therapy in sarcoidosis. It does not show methotrexate is better — it shows the choice can now be made on side effects, which for a disease often treated for years is the point.
Kahlmann V, Janssen Bonás M, Moor CC, et al. First-Line Treatment of Pulmonary Sarcoidosis with Prednisone or Methotrexate. N Engl J Med 2025 Jul 17;393(3):231-242.