New Study Finds Methotrexate a Viable Alternative to Prednisone in Initial Treatment of Pulmonary Sarcoidosis

A recent multicenter clinical trial has brought important insights into the therapeutic management of pulmonary sarcoidosis. Traditionally treated with prednisone as the first-line therapy, this condition calls for alternatives that offer similar efficacy with a reduced burden of side effects. The study, funded by the Dutch Lung Foundation, evaluated the efficacy of methotrexate compared to prednisone in patients who had never been treated for pulmonary sarcoidosis.

The open-label, randomized, non-inferiority trial included 138 patients evenly assigned to treatment groups receiving either prednisone or methotrexate. The primary outcome was the mean change from baseline to week 24 in the percentage of predicted forced vital capacity (FVC) — a key functional parameter in assessing pulmonary disease.

The results showed that methotrexate was not inferior to prednisone in improving lung function. The mean increase in predicted FVC was 6.75 percentage points in the prednisone group and 6.11 in the methotrexate group. The adjusted difference between the groups was −1.17 percentage points (95% CI: −4.27 to 1.93), falling within the pre-specified non-inferiority margin.

In terms of safety, the incidence of adverse events was similar between the two groups. However, side effect profiles differed: patients on prednisone more frequently reported weight gain, insomnia, and increased appetite, while those on methotrexate experienced nausea, fatigue, and abnormalities in liver function tests.

These findings support the viability of methotrexate as an initial treatment option for pulmonary sarcoidosis, particularly in cases where prednisone's side effects are a concern. Treatment decisions can therefore be better guided through shared decision-making between physicians and patients, taking into account both the efficacy and tolerability profiles of each therapy.

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