The researchers note limitations to their trial, including that it was conducted in a single country. “The study population in PREDMETH reflects the Dutch population, where Black, Asian and Hispanic patients are underrepresented. While we believe these results are an important basis for further research, registries and real-world studies are still needed to better understand differences in treatment response depending on genetic background,” says Dr. Wijsenbeek-Lourens.
The paper notes the PREDMETH design occurred prior to release of the 2021 ERS guideline, so its initial 40 mg/day and 15 mg/week doses of prednisone and methotrexate, respectively, differ from lower dosages endorsed by the guideline. The trial was also designed before an Indian trial that showed a 40 mg dose of prednisolone did not improve pulmonary sarcoidosis outcomes better than a 20 mg dose.4
Evidence for Less Glucocorticoid
That trial, known as SARCORT, was a single-center, open-label, randomized controlled trial of 86 patients in India who received either 20 or 40 mg daily of prednisolone over 18 months. The primary outcome was frequency of relapse or treatment failure in the high-dose group at 18 months, and secondary outcomes were time to relapse or treatment failure, overall response, change in FVC at 6 and 18 months, treatment-related adverse effects and health-related quality of life.
Patients who completed 18 months of follow-up included 86% of individuals taking the high dose and 95.3% of those taking the low dose. In the high-dose group, 46.5% had relapse or treatment failure vs. 44.2% of the low-dose group. Both groups had similar mean time to relapse or treatment failure, overall response, changes in FVC at 6 and 18 months and changes in health-related quality of life.
The SARCORT authors note, however, that their results are not generalizable because the study was conducted at a single center. They add that a 2021 British Thoracic Society statement had suggested a dose range of 20–40 mg of prednisolone.5
Choice of Drug
The SARCORT and PREDMETH trials “have been game changers in the field of sarcoidosis treatment,” says SARCORT first author Sahajal Dhooria, MD, MBBS, additional professor in the Department of Pulmonary Medicine in the Postgraduate Institute of Medical Education and Research, Chandigarh, India.
“While our trial places low-dose steroids on the same pedestal as high-dose steroids, PREDMETH goes one step ahead and takes steroid therapy off the shelf [in some cases] for sarcoidosis,” Dr. Dhooria says. He sees the trials as complementary because they both support reduced steroid dosing. However, “in the PREDMETH trial, outcomes at four weeks were much better with prednisolone.” Thus, there may be a role for short-course, low-dose prednisone treatment together with methotrexate when initiating treatment.
