PREDMETH
Trial question
Is methotrexate noninferior to prednisone in patients with pulmonary sarcoidosis?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
26.0% female
74.0% male
N = 137
137 patients (36 female, 101 male).
Inclusion criteria: patients with pulmonary sarcoidosis who had not previously received treatment.
Key exclusion criteria: previous immunosuppressive treatment for sarcoidosis; use of systemic immunosuppressive therapy in the past 3 months for another disease; primary systemic treatment indication being an extra-pulmonary location of sarcoidosis; contraindication for methotrexate or corticosteroids; pregnancy or lactation.
Interventions
N=68 methotrexate (initiation at a dose of 15 mg PO weekly, with a maximum dose of 25 mg per week).
N=69 prednisone (initiation at a dose of 40 mg PO daily, with a maintenance dose of 10 mg daily at week 16).
Primary outcome
Mean improvement in predicted forced vital capacity at week 24
6.11%
6.75%
6.8 %
5.1 %
3.4 %
1.7 %
0.0 %
Methotrexate
Prednisone
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in mean improvement in predicted FVC at week 24 (6.11% vs. 6.75%; MD -1.17, 95% CI -4.27 to 1.93).
Secondary outcomes
No significant difference in improvement in FVC at week 24 (0.25 L vs. 0.34 L; MD -0.08, 95% CI -0.25 to 0.09).
No significant difference in improvement in predicted diffusing capacity of the lungs for CO at week 24 (3.72% vs. 4.26%; MD -0.43, 95% CI -3.43 to 2.57).
No significant difference in reduction in Fatigue Assessment Scale score at week 24 (1.57 points vs. 2.62 points; MD -1.41, 95% CI -3.61 to 0.79).
Safety outcomes
No significant difference in adverse events.
Conclusion
In patients with pulmonary sarcoidosis who had not previously received treatment, methotrexate was noninferior to prednisone with respect to mean improvement in predicted FVC at week 24.
Reference
Vivienne Kahlmann, Montse Janssen Bonás, Catharina C Moor et al. First-Line Treatment of Pulmonary Sarcoidosis with Prednisone or Methotrexate. N Engl J Med. 2025 May 18. Online ahead of print.
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