Global Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy.
Chiesi USA, Inc., Cary, NC, USA.
Respir Res. 2023 Oct 6;24(1):244. doi: 10.1186/s12931-023-02549-5.
This study, in patients with symptomatic chronic obstructive pulmonary disease (COPD), explored switching therapy from non-extrafine high-dose inhaled corticosteroid/long-acting β-agonist (ICS/LABA; fluticasone propionate/salmeterol [FP/SLM]) to extrafine medium-dose beclometasone dipropionate/formoterol fumarate dihydrate/glycopyrronium (BDP/FF/G), both via dry-powder inhaler. Functional Respiratory Imaging, a quantitative computed tomography method with 3D reconstructions of pulmonary anatomy, was used to assess airway geometry and lung function.
Patients receiving a stable ICS/LABA regimen for ≥ 8 weeks were switched to FP/SLM 500/50 µg, one inhalation twice-daily (high-dose ICS) for 6 weeks. After baseline assessments (Visit 2 [V2]), therapy was switched to BDP/FF/G 100/6/10 µg, two inhalations twice-daily (medium-dose ICS) for 6 weeks, followed by V3. The primary endpoints were percentage changes in specific image-based airway volume (siV) and resistance (siR) from baseline to predose at V3 (i.e., chronic effects), assessed at total lung capacity (TLC) in central and distal lung regions. Secondary endpoints included siV and siR changes from pre-dose to post-dose at V2, and from pre-dose to post-dose at V3 at TLC (i.e., acute effects), and chronic and acute changes in siV and siR at functional residual capacity (FRC). Pre-dose forced expiratory volume in 1 s (FEV) and COPD Assessment Test (CAT) were also assessed.
There were no significant changes in pre-dose siV or siR at TLC from baseline to V3, although at FRC there was a significant decrease in mean siR in the distal airways (- 63.6%; p = 0.0261). In addition, in the distal airways there were significant acute effects at TLC on mean siV and siR (siV: 39.8% and 62.6%; siR: - 51.1% and - 57.2%, V2 and V3, respectively; all p < 0.001) and at FRC at V2 (siV: 77.9%; siR: - 67.0%; both p < 0.001). At V3, the mean change in pre-dose FEV was 62.2 mL (p = 0.0690), and in CAT total score was - 3.30 (p < 0.0001).
In patients with symptomatic COPD receiving high-dose ICS/LABA, adding a long-acting muscarinic antagonist while decreasing the ICS dose by switching to medium-dose extrafine BDP/FF/G was associated with improved airway indices, especially in the distal airways, together with improvements in respiratory health status. Trial registration ClinicalTrials.gov (NCT04876677), first posted 6th May 2021.
本研究在有症状的慢性阻塞性肺疾病（COPD）患者中，探索了从非超细高剂量吸入皮质类固醇/长效β激动剂（ICS/LABA；丙酸氟替卡松/沙美特罗[FP/SLM]）转换为超细中剂量倍氯米松二丙酸酯/富马酸福莫特罗二水合物/格隆溴铵（BDP/FF/G）的治疗方法，均通过干粉吸入器给药。功能性呼吸成像（functional Respiratory Imaging）是一种定量计算机断层扫描方法，可对肺解剖结构进行三维重建，用于评估气道几何形状和肺功能。
接受稳定 ICS/LABA 治疗方案治疗 ≥8 周的患者转换为 FP/SLM 500/50μg，每日两次吸入一次（高剂量 ICS）持续 6 周。在基线评估（访视 2[V2]）后，将治疗方案转换为 BDP/FF/G 100/6/10μg，每日两次吸入两次（中剂量 ICS）持续 6 周，然后进行 V3。主要终点是从基线到 V3 时基于特定图像的气道容积（siV）和阻力（siR）的百分比变化（即慢性影响），在中央和远端肺区的总肺活量（TLC）进行评估。次要终点包括 V2 时预剂量到后剂量的 siV 和 siR 变化，以及 V3 时预剂量到后剂量的 siV 和 siR 在 TLC（即急性影响）的变化，以及在功能残气容量（FRC）的 siV 和 siR 的慢性和急性变化。在 V2 时还评估了预剂量用力呼气 1 秒量（FEV）和 COPD 评估测试（CAT）。
从基线到 V3，TLC 处的预剂量 siV 或 siR 没有显著变化，但在 FRC 处远端气道的平均 siR 显著降低（-63.6%；p=0.0261）。此外，在 TLC 处，远端气道的 siV 和 siR 有显著的急性影响（siV：39.8%和 62.6%；siR：-51.1%和-57.2%，V2 和 V3，均 p<0.001），并且在 V2 时在 FRC 处也有显著影响（siV：77.9%；siR：-67.0%；均 p<0.001）。在 V3 时，预剂量 FEV 的平均变化为 62.2mL（p=0.0690），CAT 总评分降低了-3.30（p<0.0001）。
在接受高剂量 ICS/LABA 治疗的有症状 COPD 患者中，在切换至超细中剂量 BDP/FF/G 时加入长效抗毒蕈碱药物并降低 ICS 剂量，与气道指数的改善有关，尤其是在远端气道，同时改善了呼吸健康状况。
试验注册ClinicalTrials.gov（NCT04876677），首次于 2021 年 5 月 6 日发布。
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