The 2021 ERS pulmonary sarcoidosis treatment guideline continued to suggest prednisone or prednisolone as first-line treatment, but suggested adding methotrexate and other drugs for certain clinical situations. It recommended 20 to 40 mg of prednisone or prednisolone per day.
Methotrexate is commonly the second-line treatment for sarcoidosis and is often started if prednisone is not effective enough, cannot be tapered or causes side effects, according to Dr. Wijsenbeek-Lourens. She decided to start PREDMETH based on her personal clinical experience that methotrexate tends to cause fewer side effects than prednisone.
The researchers compared methotrexate with prednisone as initial therapy for symptomatic pulmonary sarcoidosis in an unblinded, multicenter trial without a placebo control conducted entirely within The Netherlands. They randomly assigned patients to receive either prednisone or methotrexate according to a prespecified treatment schedule. Individuals taking oral prednisone started at 40 mg daily and tapered every four weeks to 10 mg daily; individuals taking oral methotrexate started at 15 mg weekly and increased by 5 mg weekly to a maximum dose of 25 mg. The primary end point was the mean change in the percentage of the predicted forced vital capacity from baseline to week 24, as estimated with mixed models for repeated measures.
The unadjusted mean change from baseline to week 24 in the percentage of the predicted FVC was 6.75 percentage points in the prednisone group and 6.11 percentage points in the methotrexate group, with an adjusted between-group difference of –1.17 percentage points.
The researchers saw a quicker onset of action for prednisone than for methotrexate, with most FVC improvement in the prednisone group occurring four weeks from treatment start. In the methotrexate group, similar FVC improvement did not occur until week 24.
Adverse events occurred in similar percentages, with 96% of participants who took prednisone and 94% of those who took methotrexate experiencing them. Ongoing adverse events at week 24 occurred in 63% of the methotrexate group vs. 46% of the prednisone group. Ongoing elevated liver enzyme levels occurred in 25% of participants who took methotrexate, with the alanine aminotransferase level more than three times the upper limit of normal range in 9% of patients, a finding the authors say aligns with studies of methotrexate in rheumatoid arthritis patients.
But different adverse events were more common in each group of patients. At 24 weeks, individuals who took methotrexate suffered greater rates of nausea (13%) and fatigue (15%) than those who took prednisone (0% and 5%, respectively). In contrast, prednisone patients had higher rates of weight gain than methotrexate patients, at rates of 39% and 7%, respectively. Prednisone patients also had higher rates of insomnia at 24 weeks than methotrexate patients, at rates of 16% and 3%, respectively.
