Department of Respiratory Medicine, Centre of Excellence for Interstitial Lung Diseases and Sarcoidosis, Erasmus Medical Center, Rotterdam, the Netherlands.
Department of Pulmonology, ILD Center of Excellence, St. Antonius Hospital, Nieuwegein, the Netherlands.
BMC Pulm Med. 2020 Oct 19;20(1):271. doi: 10.1186/s12890-020-01290-9.
Treatment of pulmonary sarcoidosis is recommended in case of significant symptoms, impaired or deteriorating lung function. Evidence-based treatment recommendations are limited and largely based on expert opinion. Prednisone is currently the first-choice therapy and leads to short-term improvement of lung function. Unfortunately, prednisone often has side-effects and may be associated with impaired quality of life. Methotrexate is presently considered second-line therapy, and appears to have fewer side-effects.
The primary objective of this trial is to investigate the effectiveness and tolerability of methotrexate as first-line therapy in patients with pulmonary sarcoidosis compared with prednisone. The primary endpoint of this study will be the change in hospital-measured Forced Vital Capacity (FVC) between baseline and 24 weeks. Secondary objectives are to gain more insights in response to therapy in individual patients by home spirometry and patient-reported outcomes. Blood biomarkers will be examined to find predictors of response to therapy, disease progression and chronicity, and to improve our understanding of the underlying disease mechanism.
METHODS/DESIGN: In this prospective, randomized, non-blinded, multi-center, non-inferiority trial, we plan to randomize 138 treatment-naïve patients with pulmonary sarcoidosis who are about to start treatment. Patients will be randomized in a 1:1 ratio to receive either prednisone or methotrexate in a predefined schedule for 24 weeks, after which they will be followed up in regular care for up to 2 years. Regular hospital visits will include pulmonary function assessment, completion of patient-reported outcomes, and blood withdrawal. Additionally, patients will be asked to perform weekly home spirometry, and record symptoms and side-effects via a home monitoring application for 24 weeks.
This study will be the first randomized controlled trial comparing first-line treatment of prednisone and methotrexate and provide valuable data on efficacy, safety, quality of life and biomarkers. If this study confirms the hypothesis that methotrexate is as effective as prednisone as first-line treatment for sarcoidosis but with fewer side-effects, this will lead to improvement in care and initiate a change in practice. Furthermore, insights into the immunological mechanisms underlying sarcoidosis pathology might reveal new therapeutic targets.
The study was registered on the 19th of March 2020 in the International Clinical Trial Registry, www.clinicaltrials.gov; ID NCT04314193 .
有明显症状、肺功能受损或恶化的肺结节病患者，推荐进行治疗。目前，基于循证医学的治疗建议有限，主要基于专家意见。泼尼松目前是首选治疗药物，可短期改善肺功能。然而，泼尼松常伴有副作用，可能会降低生活质量。甲氨蝶呤目前被认为是二线治疗药物，副作用似乎较少。
本试验的主要目的是研究甲氨蝶呤作为肺结节病一线治疗药物与泼尼松相比的有效性和耐受性。本研究的主要终点是基线至 24 周时医院测量的用力肺活量（FVC）的变化。次要目标是通过家庭肺功能测定和患者报告的结果，更深入地了解个体患者对治疗的反应。将检查血液生物标志物，以寻找治疗反应、疾病进展和慢性的预测因子，并提高我们对潜在疾病机制的理解。
方法/设计：这是一项前瞻性、随机、非盲、多中心、非劣效性试验，我们计划对 138 名即将开始治疗的肺结节病初治患者进行随机分组。将患者按 1:1 的比例随机分为泼尼松组或甲氨蝶呤组，按既定方案接受 24 周治疗，之后在常规护理中进行 2 年的随访。常规就诊时包括肺功能评估、完成患者报告的结果以及采血。此外，患者将被要求进行每周家庭肺功能测定，并通过家庭监测应用程序记录 24 周的症状和副作用。
这将是第一项比较泼尼松和甲氨蝶呤一线治疗的随机对照试验，为疗效、安全性、生活质量和生物标志物提供有价值的数据。如果这项研究证实甲氨蝶呤作为一线治疗结节病与泼尼松同样有效，但副作用较少的假设，将改善治疗，并引发实践的改变。此外，对结节病病理免疫学机制的深入了解可能揭示新的治疗靶点。
该研究于 2020 年 3 月 19 日在国际临床试验注册中心（www.clinicaltrials.gov）注册，注册号为 NCT04314193。
