Abstract Rationale Until recently, prednisone has been the mainstay of treatment for pulmonary sarcoidosis, with methotrexate as second-line treatment. The PREDMETH randomized controlled trial (RCT) showed that methotrexate was non-inferior to prednisone with regards to lung function, health status, and symptoms after 24 weeks of treatment, but with a slower onset of efficacy. To gain more granular insights into lung function trajectory during treatment, patients performed weekly home spirometry measurements. Here, we aim to determine the time to maximal lung function improvement for prednisone and methotrexate. Methods Patients included in the multicenter PREDMETH RCT performed weekly home spirometry measurements (Forced vital capacity, FVC) using a Bluetooth enabled spirometer (Spirobank Smart, MIR, Italy) connected to an online application (Curavista, the Netherlands). Agreement between home and hospital FVC measurements was assessed using Bland-Altman analysis, and reliability was evaluated with the intraclass correlation coefficient (ICC). The Stochastic Approximation Expectation Maximization (SAEM) algorithm was applied to model whether home FVC in the prednisone and methotrexate groups reached a plateau of improvement during 24 weeks after start of treatment. Results 69 participants in the prednisone group and 67 in the methotrexate group performed home spirometry. The mean age was 47 years (SD: 12) and 73.5% of the cohort was male. Baseline characteristics were evenly distributed between the two groups. The adherence to weekly home spirometry was 88%. The overall average ICC was 0.85 (95% CI: 0.81 - 0.88). There was good agreement between home and hospital spirometry, with a mean difference of -0.16 L to -0.26 L (95% CI: -0.37L to -0.05L) at different timepoints. Both groups experienced an increase in FVC over the treatment period. The methotrexate group had a persistent linear increase in mean home FVC, and did not reach a plateau within the study period. The plateau for the prednisone group was reached on day 53 (95% CI: day 24 - day 81) (Figure 1) with a mean improvement predicted of 496ml (95% CI: 262ml - 729ml). Conclusions Home spirometry provides more detailed information on FVC trajectory after the start of prednisone and methotrexate in pulmonary sarcoidosis. While FVC reached a plateau in patients treated with prednisone within two months, FVC still linearly increased after 24 weeks in the methotrexate group, suggesting potential further improvement in FVC with continued methotrexate treatment. This analysis yields important insights for design of clinical trials and daily practice. This abstract is funded by: Dutch Lung Foundation
Simon et al. (2026) studied this question.