Comparative Effectiveness and Safety of LAMA-LABA Inhalers in Chronic Obstructive Pulmonary Disease.

IF 23.3 1区医学 Q1 MEDICINE, GENERAL & INTERNAL

JAMA Internal Medicine Pub Date : 2026-04-01 DOI:10.1001/jamainternmed.2025.8087

Gerard T Portela, Shirley V Wang, Samy Suissa, William B Feldman

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引用次数: 0

Abstract

Importance: Dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting β2-agonist (LABA) is recommended for most patients with symptomatic chronic obstructive pulmonary disease (COPD). Fixed-dose LAMA-LABA therapies are available in metered-dose, dry powder, and soft mist inhalers. However, metered-dosed inhalers are associated with greater greenhouse gas emissions than either dry powder or soft mist inhalers, and questions persist about potential intraclass differences among LAMA-LABAs given variability in their active ingredients, dosing schedules, and delivery devices.

Objective: To evaluate the comparative effectiveness and safety of once-daily umeclidinium-vilanterol dry powder inhalers, twice-daily glycopyrrolate-formoterol metered-dosed inhalers, and once-daily tiotropium-olodaterol soft mist inhalers.

Design, setting, and participants: This observational active-comparator study analyzed claims of patients (≥40 years) newly treated with LAMA-LABA inhalers and continuously enrolled in a large commercial health insurance or Medicare Advantage plan during the 183-day baseline period. Patients were propensity score matched 1:1 into 3 cohorts with index dates ranging from May 1, 2016, to February 28, 2025. Data were analyzed from July to August 2025.

Exposures: Patients treated with umeclidinium-vilanterol, glycopyrrolate-formoterol, or tiotropium-olodaterol fixed-dose inhalers.

Main outcomes and measures: Time to the first moderate or severe COPD exacerbation, major adverse cardiovascular event, urinary tract infection, and pneumonia hospitalization.

Results: The cohorts included 9479 matched pairs of patients receiving umeclidinium-vilanterol vs glycopyrrolate-formoterol (mean age, 68.9 [SD, 9.0] years; 10 319 women [54.4%]; 8636 men [45.6%]), 9598 receiving tiotropium-olodaterol vs glycopyrrolate-formoterol (mean age, 69.2 [SD, 8.7] years; 10 513 women [54.8%]; 8680 men [45.2%]), and 36 740 receiving umeclidinium-vilanterol vs tiotropium-olodaterol (mean age, 71.5 [SD, 8.4] years; 39 429 women [53.7%]; 34 044 men [46.3%]). Umeclidinium-vilanterol was associated with a 14% lower hazard of a first moderate or severe COPD exacerbation than glycopyrrolate-formoterol (hazard ratio [HR], 0.86; 95% CI, 0.81-0.91; number needed to treat [NNT], 17) and was associated with a 3% lower hazard than tiotropium-olodaterol (HR, 0.97; 95% CI, 0.94-0.99; NNT, 100). Tiotropium-olodaterol was associated with a 6% lower hazard of a first moderate or severe COPD exacerbation than glycopyrrolate-formoterol (HR, 0.94; 95% CI, 0.89-1.00). Similar risks of first major adverse cardiovascular event, urinary tract infection, and pneumonia hospitalization were observed among patients in all 3 cohorts.

Conclusions and relevance: This cohort study found that umeclidinium-vilanterol was associated with improved clinical outcomes compared with glycopyrrolate-formoterol and tiotropium-olodaterol. Patients, prescribers, and health systems may consider once-daily umeclidinium-vilanterol dry powder inhalers over alternatives among new users of LAMA-LABA therapy.

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LAMA-LABA吸入器治疗慢性阻塞性肺疾病的疗效和安全性比较

重要性：大多数有症状的慢性阻塞性肺疾病（COPD）患者推荐使用长效毒蕈碱拮抗剂（LAMA）和长效β2激动剂（LABA）双重支气管扩张治疗。固定剂量的LAMA-LABA疗法有计量、干粉和软雾吸入器。然而，与干粉吸入器或软雾吸入器相比，计量吸入器与更多的温室气体排放有关，并且由于其活性成分、给药时间表和输送装置的可变性，LAMA-LABAs之间潜在的类内差异仍然存在问题。目的：评价乌莫克利地尼-维兰特罗干粉吸入器、甘罗罗-福莫特罗计量吸入器和碘托吡罗特罗软雾吸入器的安全性和有效性比较。设计、设置和参与者：这项观察性的主动比较研究分析了在183天基线期间新接受LAMA-LABA吸入器治疗并持续参加大型商业健康保险或Medicare Advantage计划的患者（≥40岁）的索赔。将倾向评分1:1匹配的患者分为3个队列，指标日期为2016年5月1日至2025年2月28日。数据分析时间为2025年7月至8月。暴露：使用乌莫克利地尼-维兰特罗、甘罗罗-福莫特罗或替托溴铵-洛daterol固定剂量吸入器治疗的患者。主要结局和指标：到首次中度或重度COPD加重的时间、主要不良心血管事件、尿路感染和肺炎住院。结果：队列包括9479对接受乌莫克利地尼-维兰特罗vs甘罗罗-福莫特罗的患者（平均年龄68.9 [SD， 9.0]岁；10 319名女性[54.4%]；8636名男性[45.6%]），9598名接受替罗托溴-福罗特罗vs甘罗罗-福莫特罗（平均年龄69.2 [SD， 8.7]岁；10 513名女性[54.8%]；8680名男性[45.2%]），36 740名接受乌莫克利地尼-维兰特罗vs替罗托溴-福莫特罗（平均年龄71.5 [SD， 8.4]岁；39 429名女性[53.7%]；34 044名男性[46.3%]）。乌莫克利地尼-维兰特罗与首次中度或重度COPD恶化的风险比甘罗罗-福莫特罗低14%（风险比[HR]， 0.86; 95% CI, 0.81-0.91；需要治疗的人数[NNT]， 17），与噻托溴铵-洛daterol （HR, 0.97; 95% CI, 0.94-0.99； NNT, 100）相关的风险比低3%。与甘罗罗特-福莫特罗相比，噻托溴铵-洛daterol与首次中度或重度COPD恶化的风险降低6%相关（HR, 0.94; 95% CI, 0.89-1.00）。在所有3个队列的患者中，首次主要不良心血管事件、尿路感染和肺炎住院的风险相似。结论和相关性：该队列研究发现，与甘罗罗特-福莫特罗和噻托溴铵-洛daterol相比，乌莫克利地尼-维兰特罗与改善的临床结果相关。在LAMA-LABA疗法的新使用者中，患者、开处方者和卫生系统可能会考虑每日一次的乌莫克利地尼-维兰特罗干粉吸入器，而不是其他替代品。

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来源期刊

JAMA Internal Medicine MEDICINE, GENERAL & INTERNAL-

CiteScore

43.50

自引率

1.30%

发文量

371

期刊介绍： JAMA Internal Medicine is an international, peer-reviewed journal committed to advancing the field of internal medicine worldwide. With a focus on four core priorities—clinical relevance, clinical practice change, credibility, and effective communication—the journal aims to provide indispensable and trustworthy peer-reviewed evidence. Catering to academics, clinicians, educators, researchers, and trainees across the entire spectrum of internal medicine, including general internal medicine and subspecialties, JAMA Internal Medicine publishes innovative and clinically relevant research. The journal strives to deliver stimulating articles that educate and inform readers with the latest research findings, driving positive change in healthcare systems and patient care delivery. As a member of the JAMA Network, a consortium of peer-reviewed medical publications, JAMA Internal Medicine plays a pivotal role in shaping the discourse and advancing patient care in internal medicine.