Brozek Jan L, Kraft Monica, Krishnan Jerry A, Cloutier Michelle M, Lazarus Stephen C, Li James T, Santesso Nancy, Strunk Robert C, Casale Thomas B
Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Ontario, Canada.
Arch Intern Med. 2012 Oct 8;172(18):1365-75. doi: 10.1001/archinternmed.2012.3250.
Because of concerns about the safety of long-acting β(2)-agonist (LABA) use in patients with asthma, withdrawal of the LABA is recommended by the US Food and Drug Administration once asthma is controlled by combination therapy with a LABA and inhaled corticosteroid (ICS).
To perform a systematic review and meta-analysis assessing evidence supporting the discontinuation of LABA therapy once asthma control has been achieved with a combination of ICS and LABA.
MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched (through August 2010), references of identified studies and selected narrative review articles were evaluated, registries of clinical trials were reviewed, and manufacturers of LABAs were contacted.
Randomized controlled trials of discontinuation of LABA therapy in patients with asthma controlled with a combination of ICS and LABA.
Two reviewers independently screened each title and abstract in the initial searches and then the full text of each nominated article to extract data for analyses.
Of 1492 screened articles, only 5 trials involving patients aged 15 years or older fulfilled a priori–specified inclusion criteria. Results did not favor the LABA step-off approach compared with no change in treatment. The LABA step-off regimen increased asthma impairment, with worse Asthma Quality of Life Questionnaire score (mean difference [95% CI], 0.32 [0.14-0.51] points lower); worse Asthma Control Questionnaire score (0.24 [0.13-0.35] points higher); fewer symptom-free days (9.15% [1.62%-16.69%] less); and greater risk of withdrawal from study resulting from lack of efficacy or loss of asthma control (risk ratio, 3.27 [2.16-4.96]). Risk of exacerbations and deaths after LABA step-off were not evaluable because of the small number of events and short duration of follow-up.
Evidence suggests that discontinuing LABA therapy in adults and older children with asthma controlled with a combination of ICSs and LABAs results in increased asthma-associated impairment. Additional trials measuring all long-term patient-important outcomes are needed.
由于担心长效β₂受体激动剂（LABA）用于哮喘患者的安全性，美国食品药品监督管理局建议，一旦哮喘通过LABA与吸入性糖皮质激素（ICS）联合治疗得到控制，应停用LABA。
进行一项系统评价和荟萃分析，评估支持在通过ICS与LABA联合治疗实现哮喘控制后停用LABA治疗的证据。
检索了MEDLINE、EMBASE和Cochrane对照试验中央注册库数据库（截至2010年8月），评估了已识别研究的参考文献和选定的叙述性综述文章，查阅了临床试验注册库，并联系了LABA的制造商。
关于在通过ICS与LABA联合治疗控制哮喘的患者中停用LABA治疗的随机对照试验。
两名研究者在初始检索中独立筛选每个标题和摘要，然后对每篇提名文章的全文进行筛选，以提取数据进行分析。
在1492篇筛选的文章中，只有5项涉及15岁及以上患者的试验符合预先设定的纳入标准。与治疗无变化相比，结果不支持LABA逐步撤药方法。LABA逐步撤药方案增加了哮喘损害，哮喘生活质量问卷评分更差（平均差值[95%CI]，低0.32[0.14 - 0.51]分）；哮喘控制问卷评分更差（高0.24[0.13 - 0.35]分）；无症状天数更少（少9.15%[1.62% - 16.69%]）；以及因缺乏疗效或哮喘控制丧失而退出研究的风险更高（风险比，3.27[2.16 - 4.96]）。由于事件数量少和随访时间短，LABA逐步撤药后加重和死亡的风险无法评估。
有证据表明，在通过ICS与LABA联合治疗控制哮喘的成人和大龄儿童中停用LABA治疗会导致与哮喘相关的损害增加。需要进行更多测量所有对患者重要的长期结局的试验。
