Methotrexate Noninferior to Prednisone in Pulmonary Sarcoidosis Treatment: NEJM
Netherlands: In a significant development for the treatment of pulmonary sarcoidosis, researchers have found that methotrexate may be a viable alternative to prednisone as a first-line therapy. The findings, published in the New England Journal of Medicine, highlight that methotrexate is not inferior to prednisone in improving lung function over 24 weeks while presenting a distinct side-effect profile that may benefit certain patients.
Prednisone has long been considered the standard initial treatment for pulmonary sarcoidosis, primarily due to its fast-acting anti-inflammatory effects. However, its widespread use is often tempered by concerns over long-term side effects. Methotrexate, typically reserved as a second-line option, has been known for its slower onset but milder side-effect profile. This new evidence supports its use earlier in the treatment process, especially for patients who may not tolerate corticosteroids well.
The multicenter, open-label, noninferiority trial was led by Dr. Vivienne Kahlmann from the Erasmus Medical Center, Rotterdam, and involved 138 previously untreated patients with pulmonary sarcoidosis. Participants were randomly assigned to receive either prednisone or methotrexate and were followed for 24 weeks. The study's primary goal was to assess the change in forced vital capacity (FVC), a key measure of lung function.
The key findings include the following:
- By week 24, patients treated with prednisone showed an average improvement in FVC of 6.75 percentage points.
- Patients receiving methotrexate had an average FVC improvement of 6.11 percentage points.
- The adjusted difference between the two groups was -1.17 percentage points.
- This difference fell within the predefined noninferiority margin of 5 percentage points.
- Methotrexate was noninferior to prednisone in improving lung function.
- The overall incidence of adverse events was similar in both treatment groups.
- Prednisone was more commonly associated with weight gain, insomnia, and increased appetite.
- Methotrexate was more frequently linked to nausea, fatigue, and abnormal liver function tests.
The researchers emphasized that while both treatments offer clinical benefits, the differing side-effect profiles underline the importance of personalized treatment strategies. “These findings open up the possibility for patients and clinicians to engage in more informed discussions when selecting initial therapy,” the authors noted.
As sarcoidosis remains a complex and variable disease, further studies may be required to explore long-term outcomes and quality-of-life impacts associated with both treatments. However, the trial offers a promising step forward in broadening therapeutic options for individuals living with pulmonary sarcoidosis.
Reference: https://www.nejm.org/doi/full/10.1056/NEJMoa2501443
