LABA/LAMA combinations versus LAMA monotherapy or LABA/ICS in COPD: a systematic review and meta-analysis
LABA/LAMA combinations versus LAMA monotherapy or LABA/ICS in COPD: a systematic review and meta-analysis
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DOI：
10.2147/copd.s130482
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发表时间：
2017-01-01
影响因子：
2.8
通讯作者：
Kostikas, Konstantinos
中科院分区：
文献类型：
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作者：
Rodrigo, Gustavo J.;Price, David;Kostikas, Konstantinos
背景：随机对照试验(RCT)表明，与常用的COPD治疗方法相比，长效的支气管扩张剂组合，如β2-激动剂(LABA)/M受体拮抗剂(LAMA)，具有良好的疗效。本分析的目的是比较LABA/LAMA与LABA/LAMA或LABA/吸入皮质类固醇(ICS)治疗稳定的中重度COPD的疗效和安全性。方法：这项系统综述和荟萃分析(PubMed/MEDLINE，Embase，Cochrane Library和临床试验/制造商数据库)包括RCT比较。LABA/LAMA治疗12周，使用LAMA和/或LABA/ICS(仅批准剂量)。符合条件的研究由两位作者使用预定义的数据字段独立选择；系统综述和Meta分析指南的首选报告项目如下。结果：18项研究(23项试验)符合条件(N=20185)。从基线到第12周，LABA/LAMA的1秒用力呼气量(FEV1)较LABA/ICS显著改善(0.07 L和0.08 L，P.0.0001)，患者更有可能在FEV1方面取得临床重要的改善。100毫升(风险比[RR]：1.33，95%可信区间[CI]：[1.20，1.46]和RR：1.44，95%CI：[1.33，1.56]，需要治疗的数量分别为8和6)。与LABA/ICS相比，LABA/LAMA在12周时改善了过渡性呼吸困难指数和圣乔治呼吸问卷评分(P均为0.0001)，但与LABA/ICS相比无明显改善，并减少了抢救药物的使用(分别为P<0.0001和P=0.001)。LABA/LAMA组较LABA/ICS组中、重度恶变率显著降低(RR 0.82，95%CI：0.75，0.91)。LABA/LAMA和LAMA治疗的不良事件(AE)发生率没有差异，但低于LABA/ICS(RR 0.94，95%CI：[0.89，0.99])，包括较低的肺炎风险(RR 0.59，95%CI：[0.43，0.81])。LABA/LAMA较LAMA无效(RR：0.66，95%CI：[0.51，0.87])，AEs较LABA/ICS无效(RR：0.83，95%CI：[0.69，0.99])。结论：与LAMA或LABA/ICS相比，LABA/LAMA具有更好的疗效和相似的安全性，支持它们作为COPD一线治疗方案的潜在作用。这些发现与临床实践直接相关，因为我们包括了目前所有可用的LABA/LAMA和比较器，只有在批准临床使用的剂量下。
Background: Randomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as beta 2-agonist (LABA)/muscarinic antagonist (LAMA), have favorable efficacy compared with commonly used COPD treatments. The objective of this analysis was to compare the efficacy and safety of LABA/LAMA with LAMA or LABA/inhaled corticosteroid (ICS) in adults with stable moderate-to-very-severe COPD.Methods: This systematic review and meta-analysis (PubMed/MEDLINE, Embase, Cochrane Library and clinical trial/manufacturer databases) included RCTs comparing. 12 weeks' LABA/ LAMA treatment with LAMA and/or LABA/ICS (approved doses only). Eligible studies were independently selected by two authors using predefined data fields; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.Results: Eighteen studies (23 trials) were eligible (N= 20,185). LABA/LAMA significantly improved trough forced expiratory volume in 1 second (FEV1) from baseline to week 12 versus both LAMA and LABA/ICS (0.07 L and 0.08 L, P. 0.0001), with patients more likely to achieve clinically important improvements in FEV1 of. 100 mL (risk ratio[RR]: 1.33, 95% confidence interval[CI]:[1.20, 1.46] and RR: 1.44, 95% CI:[1.33, 1.56], respectively, the number needed to treat being eight and six, respectively). LABA/LAMA improved transitional dyspnea index and St George's Respiratory Questionnaire scores at week 12 versus LAMA (both P. 0.0001), but not versus LABA/ICS, and reduced rescue medication use versus both (P. 0.0001 and P= 0.001, respectively). LABA/LAMA significantly reduced moderate/severe exacerbation rate compared with LABA/ICS (RR 0.82, 95% CI:[0.75, 0.91]). Adverse event (AE) incidence was no different for LABA/LAMA versus LAMA treatment, but it was lower versus LABA/ICS (RR 0.94, 95% CI: [0.89, 0.99]), including a lower pneumonia risk (RR 0.59, 95% CI:[0.43, 0.81]). LABA/LAMA presented a lower risk for withdrawals due to lack of efficacy versus LAMA (RR: 0.66, 95% CI: [0.51, 0.87]) and due to AEs versus LABA/ICS (RR: 0.83, 95% CI:[0.69, 0.99]).Conclusion: The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD. These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use.