Observational & Pragmatic Research Institute Pte Ltd, Singapore, Singapore.
Data to Insights Research Solutions, Lisbon, Portugal.
Int J Chron Obstruct Pulmon Dis. 2020 Oct 29;15:2739-2750. doi: 10.2147/COPD.S269287. eCollection 2020.
This study aimed to evaluate the non-inferiority of initiating extrafine beclometasone dipropionate/formoterol fumarate (BDP/FF) versus double bronchodilation (long-acting beta-agonists [LABA]/long-acting muscarinic antagonists [LAMA]) among patients with a history of chronic obstructive pulmonary disease (COPD) exacerbations.
A historical cohort study was conducted using data from the UK's Optimum Patient Care Research Database. Patients with COPD ≥40 years at diagnosis were included if they initiated extrafine BDP/FF or any LABA/LAMA double therapy as a step-up from no maintenance therapy or monotherapy with inhaled corticosteroids (ICS), LAMA, or LABA and a history of ≥2 moderate/severe exacerbations in the previous two years. The primary outcome was exacerbation rate from therapy initiation until a relevant therapy change or end of follow-up. Secondary outcomes included rate of acute respiratory events, acute oral corticosteroids (OCS) courses, and antibiotic prescriptions with lower respiratory indication, modified Medical Research Council score (mMRC) ≥2, and time to first pneumonia diagnosis. The non-inferiority boundary was set at a relative difference of 15% on the ratio scale. Five potential treatment effect modifiers were investigated.
A total of 1735 patients initiated extrafine BDP/FF and 2450 patients initiated LABA/LAMA. The mean age was 70 years, 51% were male, 41% current smokers, and 85% had FEV <80% predicted. Extrafine BDP/FF showed non-inferiority to LABA/LAMA for rate of exacerbations (incidence rate ratio [IRR] = 1.01 [95% CI 0.94-1.09]), acute respiratory events (IRR = 0.98 [0.92-1.04]), acute OCS courses (IRR = 1.01 [0.91-1.11]), and antibiotic prescriptions (IRR = 0.99 [0.90-1.09]), but not for mMRC (OR = 0.93 [0.69-1.27]) or risk of pneumonia (HR = 0.50 [0.14-1.73]). None of the a priori defined effect modifier candidates affected the comparative effectiveness.
This study found that stepping up to extrafine BDP/FF from no maintenance or monotherapy was not inferior to stepping up to double bronchodilation therapy in patients with a history of exacerbations.
本研究旨在评估在有慢性阻塞性肺疾病（COPD）加重史的患者中，起始使用超细布地奈德/福莫特罗（BDP/FF）与起始双支气管扩张治疗（长效β-激动剂[LABA]/长效抗毒蕈碱拮抗剂[LAMA]）相比的非劣效性。
采用来自英国 Optimum Patient Care Research Database 的数据进行历史队列研究。如果患者在诊断≥40 岁时开始使用超细 BDP/FF 或任何 LABA/LAMA 双重治疗，作为无维持治疗或吸入皮质类固醇（ICS）、LAMA 或 LABA 单药治疗的升级治疗，且在过去两年中有≥2 次中度/重度加重史，则将其纳入研究。主要结局是从治疗开始到相关治疗改变或随访结束时的加重率。次要结局包括急性呼吸道事件、急性口服皮质类固醇（OCS）疗程、有下呼吸道指征的抗生素处方、改良的医学研究委员会评分（mMRC）≥2 分和首次肺炎诊断的时间。非劣效性边界设定为比率标度上的相对差异 15%。研究调查了 5 个潜在的治疗效果修饰因子。
共有 1735 例患者起始超细 BDP/FF 治疗，2450 例患者起始 LABA/LAMA 治疗。平均年龄为 70 岁，51%为男性，41%为当前吸烟者，85%的患者有 FEV <80%预计值。超细 BDP/FF 治疗在加重率（发病率比[IRR] = 1.01 [95%CI 0.94-1.09]）、急性呼吸道事件（IRR = 0.98 [0.92-1.04]）、急性 OCS 疗程（IRR = 1.01 [0.91-1.11]）和抗生素处方（IRR = 0.99 [0.90-1.09]）方面与 LABA/LAMA 相比非劣效，但在 mMRC（OR = 0.93 [0.69-1.27]）或肺炎风险（HR = 0.50 [0.14-1.73]）方面不劣效。之前定义的治疗效果修饰因子候选者均不影响比较效果。
本研究发现，在有加重史的患者中，从无维持或单药治疗升级至超细 BDP/FF 治疗与升级至双支气管扩张治疗相比非劣效。
