Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, 1873 Rama IV Road, Patumwan, Bangkok, 10330, Thailand.
University of Western Australia, Royal Perth Hospital, Perth, Australia.
Adv Ther. 2023 Jan;40(1):133-158. doi: 10.1007/s12325-022-02356-2. Epub 2022 Nov 8.
Short-acting β-agonist (SABA) reliever overuse is common in asthma, despite availability of inhaled corticosteroid (ICS)-based maintenance therapies, and may be associated with increased risk of adverse events (AEs). This systematic literature review (SLR) and meta-analysis aimed to investigate the safety and tolerability of SABA reliever monotherapy for adults and adolescents with asthma, through analysis of randomized controlled trials (RCTs) and real-world evidence.
An SLR of English-language publications between January 1996 and December 2021 included RCTs and observational studies of patients aged ≥ 12 years treated with inhaled SABA reliever monotherapy (fixed dose or as needed) for ≥ 4 weeks. Studies of terbutaline and fenoterol were excluded. Meta-analysis feasibility was dependent on cross-trial data comparability. A random-effects model estimated rates of mortality, serious AEs (SAEs), and discontinuation due to AEs (DAEs) for as-needed and fixed-dose SABA treatment groups. ICS monotherapy and SABA therapy were compared using a fixed-effects model.
Forty-two studies were identified by the SLR for assessment of feasibility. Final meta-analysis included 24 RCTs. Too few observational studies (n = 2) were available for inclusion in the meta-analysis. One death unrelated to treatment was reported in each of the ICS, ICS + LABA, and fixed-dose SABA groups. No other treatment-related deaths were reported. SAE and DAE rates were < 4%. DAEs were reported more frequently in the SABA treatment groups than with ICS, potentially owing to worsening asthma symptoms being classified as an AE. SAE risk was comparable between SABA and ICS treatments.
Meta-analysis of data from RCTs showed that deaths were rare with SABA reliever monotherapy, and rates of SAEs and DAEs were comparable between SABA reliever and ICS treatment groups. When used appropriately within prescribed limits as reliever therapy, SABA does not contribute to excess rates of mortality, SAEs, or DAEs.
尽管有吸入皮质类固醇（ICS）维持疗法可用，但短效β-激动剂（SABA）缓解剂的过度使用在哮喘中仍很常见，并且可能与不良事件（AE）风险增加相关。本系统文献回顾（SLR）和荟萃分析旨在通过分析随机对照试验（RCT）和真实世界证据，研究 SABA 缓解剂单药治疗成人和青少年哮喘的安全性和耐受性。
本 SLR 纳入了 1996 年 1 月至 2021 年 12 月期间发表的英语文献，包括接受吸入性 SABA 缓解剂单药治疗（固定剂量或按需）≥4 周的年龄≥12 岁患者的 RCTs 和观察性研究。排除了特布他林和非诺特罗的研究。荟萃分析的可行性取决于跨试验数据的可比性。随机效应模型估计按需和固定剂量 SABA 治疗组的死亡率、严重不良事件（SAE）和因 AE 停药（DAE）的发生率。使用固定效应模型比较 ICS 单药和 SABA 治疗。
通过 SLR 评估可行性后，共确定了 42 项研究。最终荟萃分析纳入了 24 项 RCT。纳入荟萃分析的观察性研究太少（n=2）。ICS、ICS+LABA 和固定剂量 SABA 组各报告了 1 例与治疗无关的死亡。未报告其他与治疗相关的死亡。SAE 和 DAE 发生率均<4%。与 ICS 相比，SABA 治疗组报告的 DAE 更为频繁，这可能是由于将哮喘症状恶化归类为 AE。SABA 和 ICS 治疗的 SAE 风险相当。
对 RCT 数据的荟萃分析显示，SABA 缓解剂单药治疗的死亡率罕见，SABA 缓解剂和 ICS 治疗组的 SAE 和 DAE 发生率相当。在规定的缓解治疗范围内合理使用时，SABA 不会导致死亡率、SAE 或 DAE 发生率增加。
