Centre for Clinical Epidemiology, Lady Davis Institute - Jewish General Hospital; and the Department of Epidemiology and Biostatistics, McGill University, Montreal, QC, Canada.
Centre for Clinical Epidemiology, Lady Davis Institute - Jewish General Hospital; and the Department of Epidemiology and Biostatistics, McGill University, Montreal, QC, Canada.
Chest. 2020 Apr;157(4):846-855. doi: 10.1016/j.chest.2019.11.007. Epub 2019 Nov 22.
Triple therapy combinations of a long-acting muscarinic antagonist (LAMA), a long-acting beta-agonist (LABA), and an inhaled corticosteroid (ICS) for COPD were studied in randomized trials and observational studies, with variable results. We compared the effectiveness and safety of triple therapy with a LAMA-LABA combination in a real-world clinical practice setting.
We identified a cohort of patients with COPD during 2002 through 2015, ≥ 55 years of age, from the UK's Clinical Practice Research Datalink. Patients initiating LAMA-LABA-ICS were matched 4:1 on time-conditional propensity scores with patients initiating LAMA-LABA, and followed for 1 year for the occurrence of a moderate or severe COPD exacerbation and severe pneumonia.
The cohort included 6,921 initiators of LAMA-LABA-ICS matched to 1,932 initiators of LAMA-LABA. The adjusted hazard ratio (HR) of a COPD exacerbation associated with LAMA-LABA-ICS initiation compared with LAMA-LABA initiation was 0.97 (95% CI, 0.87-1.08). For patients with blood eosinophil counts > 6%, the HR was 0.66 (95% CI, 0.46-0.94). For patients with two or more prior exacerbations, it was 0.83 (95% CI, 0.70-0.98). The incidence of severe pneumonia requiring hospitalization was increased with LAMA-LABA-ICS initiation (HR, 1.46; 95% CI, 1.03-2.06).
In a real-world setting of COPD treatment, the triple combination of LAMA, LABA, and ICS inhalers is generally as effective as combining LAMA and LABA inhalers in preventing COPD exacerbations. However, with the possible exception of patients with significant eosinophilia or frequent exacerbators, a LAMA-LABA combination without ICS may be preferable because it is associated with fewer severe cases of pneumonia.
长效毒蕈碱拮抗剂（LAMA）、长效β-激动剂（LABA）和吸入皮质类固醇（ICS）三联疗法治疗 COPD 的随机试验和观察性研究结果不一。我们在真实临床实践环境中比较三联疗法与 LAMA-LABA 联合治疗的有效性和安全性。
我们从英国临床实践研究数据链中确定了一个 2002 年至 2015 年期间年龄≥55 岁的 COPD 患者队列。按时间条件倾向评分将起始 LAMA-LABA-ICS 的患者与起始 LAMA-LABA 的患者以 4:1 匹配，并随访 1 年以观察中重度 COPD 加重和重度肺炎的发生情况。
队列包括 6921 例起始 LAMA-LABA-ICS 的患者和 1932 例起始 LAMA-LABA 的患者。与起始 LAMA-LABA 相比，起始 LAMA-LABA-ICS 与 COPD 加重的调整后的危险比（HR）为 0.97（95%CI，0.87-1.08）。对于血嗜酸性粒细胞计数>6%的患者，HR 为 0.66（95%CI，0.46-0.94）。对于有两次或更多既往加重的患者，HR 为 0.83（95%CI，0.70-0.98）。起始 LAMA-LABA-ICS 治疗时，严重肺炎需要住院治疗的发生率增加（HR，1.46；95%CI，1.03-2.06）。
在 COPD 治疗的真实世界环境中，LAMA、LABA 和 ICS 吸入器的三联组合通常与 LAMA 和 LABA 吸入器联合预防 COPD 加重一样有效。然而，除了血嗜酸性粒细胞计数显著升高或频繁加重的患者外，不使用 ICS 的 LAMA-LABA 联合治疗可能更为可取，因为它与较少的严重肺炎病例相关。
