布地奈德/格隆溴铵/富马酸福莫特罗气雾剂治疗 COPD 的骨和眼部安全性：一项 52 周随机研究。
Bone and ocular safety of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler in COPD: a 52-week randomized study.
机构信息
Clinical Research Institute of Southern Oregon, 3860 Crater Lake Avenue, Medford, OR, 97504, USA.
Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA.
出版信息
Respir Res. 2019 Jul 29;20(1):167. doi: 10.1186/s12931-019-1126-7.
BACKGROUND
Long-term use of inhaled corticosteroids (ICSs) has been associated with increased risk of bone and ocular comorbidities. We evaluated the effects of the triple fixed-dose combination budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI), formulated using co-suspension delivery technology, on bone mineral density (BMD) and ocular safety in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD).
METHODS
In this extension study, a subset of patients from the 24-week, phase III, randomized, double-blind KRONOS study (NCT02497001) continued treatment (BGF MDI 320/18/9.6 μg, budesonide/formoterol fumarate [BFF] MDI 320/9.6 μg or glycopyrrolate/formoterol fumarate [GFF] MDI 18/9.6 μg, as a non-steroidal comparator) for an additional 28 weeks. Primary endpoints were percentage change from baseline in lumbar spine BMD and change from baseline in lens opacities classification system III posterior subcapsular cataract (P) score, both at Week 52. Adverse events were also assessed.
RESULTS
In total, 456 patients were included in the safety population (53.1% male, mean age 62.8 years). Changes from baseline in lumbar spine BMD (least squares mean [LSM] range - 0.12 to 0.38%) and P score (LSM range 0.02-0.15) were small for all treatments. Both BGF MDI and BFF MDI were non-inferior to GFF MDI using margins of -2% (BMD) and 0.5 units (P score). The incidence of treatment-emergent adverse events (TEAEs) was generally similar among groups. Rates of confirmed pneumonia were low overall (2.4%) and highest in the GFF MDI group (3.4%), followed by BGF MDI (2.1%) and BFF MDI (1.1%). There were no cumulative adverse effects of treatment over time as the incidence and types of TEAEs, were generally similar in the first 24 weeks of the study and after Week 24.
CONCLUSIONS
In patients with COPD, both ICS-containing therapies were non-inferior to GFF MDI for the primary BMD and ophthalmological endpoints. Changes from baseline in all three treatment groups over 52 weeks were small and not clinically meaningful. All treatments were well tolerated with no new or unexpected safety findings.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02536508. Registered 27 August 2015.
背景
长期使用吸入性皮质类固醇（ICSs）与骨和眼部合并症的风险增加有关。我们评估了三重固定剂量组合布地奈德/格隆溴铵/福莫特罗富马酸盐计量吸入器（BGF MDI），该组合使用共悬浮输送技术，对中重度至重度慢性阻塞性肺疾病（COPD）患者的骨密度（BMD）和眼部安全性的影响。
方法
在这项扩展研究中，来自 24 周、III 期、随机、双盲 KRONOS 研究（NCT02497001）的患者亚组继续接受治疗（BGF MDI 320/18/9.6μg、布地奈德/福莫特罗富马酸盐[BFF]MDI 320/9.6μg 或格隆溴铵/福莫特罗富马酸盐[GFF]MDI 18/9.6μg，作为非甾体类对照），持续 28 周。主要终点是第 52 周时腰椎 BMD 从基线的百分比变化和 lens opacities classification system III 后囊下白内障（P）评分的从基线的变化，均在第 52 周时进行评估。还评估了不良事件。
结果
总共纳入了 456 名患者（53.1%为男性，平均年龄 62.8 岁）。所有治疗的腰椎 BMD（最小二乘均值[LSM]范围-0.12%至 0.38%）和 P 评分（LSM 范围 0.02%至 0.15%）的变化均较小。使用-2%（BMD）和 0.5 个单位（P 评分）的边界，BGF MDI 和 BFF MDI 均与 GFF MDI 非劣效。各组治疗中出现的不良事件（TEAEs）发生率总体相似。总的来说，肺炎的确诊发生率较低（2.4%），GFF MDI 组最高（3.4%），其次是 BGF MDI 组（2.1%）和 BFF MDI 组（1.1%）。随着时间的推移，治疗没有累积不良影响，因为在研究的前 24 周和第 24 周后，TEAEs 的发生率和类型通常相似。
结论
在 COPD 患者中，含有 ICS 的两种治疗方法在原发性 BMD 和眼科终点方面均不劣于 GFF MDI。所有三组治疗在 52 周时与基线相比的变化较小，且无临床意义。所有治疗均耐受良好，无新的或意外的安全性发现。
临床试验注册号
ClinicalTrials.gov NCT02536508。登记日期：2015 年 8 月 27 日。
Zotero 插件