Noorduyn Stephen G, Begaj Kejsi, Martin Amber, Forero-Schwanhaeuser Sergio, Schaible Kassandra, Moore Alison, Paczkowski Rosirene
Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.
Global Real-World Evidence & Health Outcomes Research Organization, GSK, 100 Milverton Drive Suite 800, Mississauga, ON, Canada.
Pulm Ther. 2025 Jun;11(2):159-176. doi: 10.1007/s41030-025-00288-0. Epub 2025 Mar 6.
Long-acting muscarinic antagonist (LAMA) addition to inhaled corticosteroid/long-acting β-agonist (ICS/LABA) dual therapy is recommended for severe asthma, but its real-world effectiveness is not well established.
A systematic literature review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to investigate clinical outcomes in US adults with asthma receiving ICS + LABA + LAMA as multiple-/single-inhaler triple therapy (MITT/SITT). Real-world/observational studies published in English in Embase/MEDLINE databases (2014-2024) and conference abstracts presented 2022-2024 were eligible for inclusion.
From 588 identified records, only 8 articles reporting 6 unique studies were included; 2 assessed SITT and 4 assessed MITT, and 4 treatments were investigated. Exacerbation rates reported in two studies were significantly reduced with tiotropium (TIO) + ICS + LABA MITT versus high-dose ICS + LABA within 6 (64% lower) and 12 months (73%), and fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg SITT versus pre-treatment after 12 months (41%). Oral corticosteroid (OCS) use was reported in two studies. The proportion of patients with ≥ 1 rescue OCS dispensing decreased with TIO 1.25 mcg + ICS + LABA MITT, with greatest reductions for MITT ± leukotriene receptor antagonist (pre-treatment: 68.4%, post treatment: 54.2%). Mean number of OCS dispensings/patient/year significantly decreased (29%, p < 0.001) following FF/UMEC/VI 100/62.5/25 mcg SITT initiation. Treatment adherence/persistence was reported in three studies. Mean (standard deviation) proportion of days covered was significantly higher (p < 0.001) for FF/UMEC/VI SITT versus MITT after 6 (0.56 [0.31] versus 0.46 [0.31]) and 12 months (0.46 [0.33] versus 0.35 [0.30]). Persistence at 12 months was 25.9% and 12.0%, respectively. Lung function, clinical remission, quality of life, and safety outcomes were not reported in any study.
This brief communication reports a systematic review that identified few sources of SITT or MITT in US patients with asthma. Although inclusion of observational studies can result in reporting/selection bias, we identified greater clinical benefits with triple therapies versus dual therapies.
对于重度哮喘，建议在吸入性糖皮质激素/长效β受体激动剂（ICS/LABA）双重治疗基础上加用长效毒蕈碱拮抗剂（LAMA），但其在现实世界中的有效性尚未得到充分证实。
根据系统评价和Meta分析的首选报告项目（PRISMA）进行系统文献综述，以调查美国成年哮喘患者接受ICS + LABA + LAMA作为多吸入器/单吸入器三联疗法（MITT/SITT）的临床结局。2014年至2024年在Embase/MEDLINE数据库中以英文发表的现实世界/观察性研究以及2022年至2024年发表的会议摘要均符合纳入标准。
从588条已识别记录中，仅纳入了8篇报告6项独特研究的文章；2项评估了SITT，4项评估了MITT，且研究了4种治疗方法。两项研究报告，噻托溴铵（TIO）+ ICS + LABA MITT与高剂量ICS + LABA相比，在6个月（降低64%）和12个月（降低73%）时，急性加重率显著降低；糠酸氟替卡松/乌美溴铵/维兰特罗（FF/UMEC/VI）100/62.5/25 mcg SITT与治疗前相比，12个月后急性加重率降低41%。两项研究报告了口服糖皮质激素（OCS）的使用情况。使用1.25 mcg TIO + ICS + LABA MITT时，≥1次急救OCS配药的患者比例降低，MITT±白三烯受体拮抗剂时降低幅度最大（治疗前：68.4%，治疗后：54.2%）。开始使用FF/UMEC/VI 100/62.5/25 mcg SITT后，每位患者每年的OCS配药平均次数显著减少（29%，p < 0.001）。三项研究报告了治疗依从性/持续性。6个月（0.56 [0.31] 对0.46 [0.31]）和12个月（0.46 [0.33] 对0.35 [0.30]）后，FF/UMEC/VI SITT的平均（标准差）覆盖天数比例显著高于MITT。12个月时的持续性分别为25.9%和12.0%。任何研究均未报告肺功能、临床缓解、生活质量和安全性结局。
本简要通讯报告了一项系统综述，该综述发现美国哮喘患者中SITT或MITT的资料很少。尽管纳入观察性研究可能会导致报告/选择偏倚，但我们发现三联疗法比双重疗法具有更大的临床益处。
