Methotrexate vs. Prednisone as the First Line Treatment for Pulmonary Sarcoidosis
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on August 6th, 2025
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Prednisone is the first-line therapy to treat the inflammation associated with pulmonary sarcoidosis. However, this treatment is recommended based on dated and low quality studies. Additionally, prolonged prednisone usage is associated with significant side effects. Recently, a study funded by the Dutch Lung Foundation was conducted to evaluate the replacement of prednisone with methotrexate in treating pulmonary sarcoidosis.
The clinical study included 137 participants who had been diagnosed with pulmonary sarcoidosis. The Scadding criteria was used to assess disease severity at baseline: 75% of participants were at stage 2 with bilateral hilar lymphadenopathy, with the remaining at either stage 3 with pulmonary infiltrates or pulmonary fibrosis of stage 4. Baseline spirometry evaluation found that cohort to have an average force vital capacity of 3.7 liters and a force expiratory volume in 1 second of 2.66 liters.
The patients were randomly assigned to be treated orally with either prednisone or methotrexate. The former was given at an initial daily dose of 40 mg that is reduced every 4 weeks until reaching a maintenance dose of 10 mg at week 16. Methotrexate was given a dose escalation schedule starting at 15 mg per week until reaching a maximum dose of 25 mg if tolerated well. After 24 weeks of treatment, the researchers found that both prednisone and methotrexate resulted in similar improvement in lung function as measured by an average 6% increase in forced vital lung capacity. This similarity in clinical improvement is also reported with other patients’ reported parameters such as fatigue and the King’s Sarcoidosis Questionnaire. It is important to note that prednisone leads to rapid improvement in lung function; however, this change is not sustainable. Whereas, the degree of clinical improvement of methotrexate happens more gradually. Side effects analysis found that prednisone is associated with a higher risk of weight gain and methotrexate patients reported a higher frequency of fatigue and elevated liver enzyme.
The clinical study included 137 participants who had been diagnosed with pulmonary sarcoidosis. The Scadding criteria was used to assess disease severity at baseline: 75% of participants were at stage 2 with bilateral hilar lymphadenopathy, with the remaining at either stage 3 with pulmonary infiltrates or pulmonary fibrosis of stage 4. Baseline spirometry evaluation found that cohort to have an average force vital capacity of 3.7 liters and a force expiratory volume in 1 second of 2.66 liters.
The patients were randomly assigned to be treated orally with either prednisone or methotrexate. The former was given at an initial daily dose of 40 mg that is reduced every 4 weeks until reaching a maintenance dose of 10 mg at week 16. Methotrexate was given a dose escalation schedule starting at 15 mg per week until reaching a maximum dose of 25 mg if tolerated well. After 24 weeks of treatment, the researchers found that both prednisone and methotrexate resulted in similar improvement in lung function as measured by an average 6% increase in forced vital lung capacity. This similarity in clinical improvement is also reported with other patients’ reported parameters such as fatigue and the King’s Sarcoidosis Questionnaire. It is important to note that prednisone leads to rapid improvement in lung function; however, this change is not sustainable. Whereas, the degree of clinical improvement of methotrexate happens more gradually. Side effects analysis found that prednisone is associated with a higher risk of weight gain and methotrexate patients reported a higher frequency of fatigue and elevated liver enzyme.