注射用促肾上腺皮质激素治疗肺结节病的4期多中心随机双盲安慰剂对照研究结果
Results From a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Repository Corticotropin Injection for the Treatment of Pulmonary Sarcoidosis.
作者信息
Mirsaeidi Mehdi, Baughman Robert P, Sahoo Debasis, Tarau Eva
机构信息
College of Medicine-Jacksonville, University of Florida, Jacksonville, FL, USA.
University of Cincinnati Medical Center, Cincinnati, OH, 45267-0565, USA.
出版信息
Pulm Ther. 2023 Jun;9(2):237-253. doi: 10.1007/s41030-023-00222-2. Epub 2023 Apr 19.
INTRODUCTION
Long-term treatment of pulmonary sarcoidosis with glucocorticoids has been associated with toxicity and other adverse events, highlighting the need for alternative therapies. The goal of this study was to evaluate the efficacy and safety of repository corticotropin injection (RCI, Acthar Gel) in patients with pulmonary sarcoidosis and to validate endpoints for use in future clinical trials.
METHODS
In this multicenter, randomized, placebo-controlled trial, subjects received subcutaneous RCI (80 U) twice weekly or matching placebo through 24 weeks in a double-blind treatment phase, followed by an optional 24-week open-label extension. Efficacy was measured by glucocorticoid tapering, pulmonary function tests, chest imaging, patient-reported outcomes, and a novel sarcoidosis treatment score (STS). Safety was assessed by adverse events, physical examinations, vital signs, clinical laboratory abnormalities, and imaging. The study was terminated early due to low enrollment caused by the COVID-19 pandemic, thereby precluding statistical analysis.
RESULTS
Fifty-five subjects were randomized to receive either RCI (n = 27) or placebo (n = 28). Mean STS at week 24 showed greater improvement with RCI (1.4) compared with placebo (0.7). At week 48, those who remained on RCI had an STS of 1.8 compared with 0.9 in those who switched from placebo to RCI. More subjects in the RCI group discontinued glucocorticoids at week 24 compared to the placebo group. Glucocorticoid discontinuation was comparable at week 48 for those who switched from placebo to RCI and those who continued RCI. Similar trends in favor of RCI over placebo were observed with the other efficacy endpoints. No new or unexpected safety signals were identified.
CONCLUSIONS
RCI was safe and well tolerated, with trends in efficacy data suggesting greater improvement with RCI compared to placebo in patients receiving standard-of-care therapy for pulmonary sarcoidosis. The study also provided validation of efficacy endpoints that may be used in larger trials for pulmonary sarcoidosis.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT03320070.
引言
长期使用糖皮质激素治疗肺结节病与毒性及其他不良事件相关，这凸显了对替代疗法的需求。本研究的目的是评估长效促肾上腺皮质激素注射液（RCI，商品名Acthar Gel）治疗肺结节病患者的疗效和安全性，并验证可用于未来临床试验的终点指标。
方法
在这项多中心、随机、安慰剂对照试验中，受试者在为期24周的双盲治疗阶段接受每周两次皮下注射RCI（80单位）或匹配的安慰剂，随后是一个为期24周的开放标签延长期。疗效通过糖皮质激素减量、肺功能测试、胸部影像学检查、患者报告的结果以及一个新的结节病治疗评分（STS）来衡量。安全性通过不良事件、体格检查、生命体征、临床实验室异常和影像学检查进行评估。由于COVID-19大流行导致入组率低，该研究提前终止，因此无法进行统计分析。
结果
55名受试者被随机分配接受RCI（n = 27）或安慰剂（n = 28）。与安慰剂组（0.7）相比，第24周时RCI组的平均STS改善更大（1.4）。在第48周时，继续使用RCI的患者的STS为1.8，而从安慰剂组转为RCI组的患者的STS为0.9。与安慰剂组相比，RCI组在第24周时有更多受试者停用糖皮质激素。对于从安慰剂组转为RCI组的患者和继续使用RCI的患者，第48周时糖皮质激素停用情况相当。在其他疗效终点方面，也观察到了RCI优于安慰剂的类似趋势。未发现新的或意外的安全信号。
结论
RCI安全且耐受性良好，疗效数据趋势表明，与安慰剂相比，接受标准治疗的肺结节病患者使用RCI的改善更大。该研究还验证了可用于更大规模肺结节病试验的疗效终点指标。
试验注册
ClinicalTrials.gov标识符：NCT03320070。
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