Hatter Lee, Bruce Pepa, Braithwaite Irene, Holliday Mark, Fingleton James, Weatherall Mark, Beasley Richard
Medical Research Institute of New Zealand, Wellington, New Zealand.
National Heart and Lung Institute, Imperial College London, London, UK.
ERJ Open Res. 2021 Jan 25;7(1). doi: 10.1183/23120541.00701-2020. eCollection 2021 Jan.
The Global Initiative for Asthma recommends as-needed inhaled corticosteroid (ICS)-formoterol as an alternative to maintenance ICS plus short-acting β-agonist (SABA) reliever at step 2 of its stepwise treatment algorithm. Our aim was to assess the efficacy and safety of these two treatment regimens, with a focus on prevention of severe exacerbation.
We performed a systematic review and meta-analysis of all randomised controlled trials (RCTs) comparing as-needed ICS-formoterol with maintenance ICS plus SABA. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrials.gov were searched from database inception to 12 December 2019. The primary outcome was time to first severe exacerbation. RCTs were excluded if they used as-needed budesonide-formoterol as part of a maintenance and reliever regimen, or did not report on severe exacerbations. The review is registered with PROSPERO (identifier number CRD42020154680).
Four RCTs (n=8065 participants) were included in the analysis. As-needed ICS-formoterol was associated with a prolonged time to first severe exacerbation (hazard ratio 0.85, 95% CI 0.73-1.00; p=0.048) and reduced daily ICS dose (mean difference -177.3 μg, 95% CI -182.2--172.4 μg). Asthma symptom control was worse in the as-needed group (Asthma Control Questionnaire-5 mean difference 0.12, 95% CI 0.09-0.14), although this did not meet the minimal clinically important difference of 0.50 units. There was no significant difference in serious adverse events (OR 1.07, 95% CI 0.84-1.36).
As-needed ICS-formoterol offers a therapeutic alternative to maintenance low-dose ICS plus SABA in asthma and may be the preferred option when prevention of severe exacerbation is the primary aim of treatment.
全球哮喘防治创议推荐按需使用吸入性糖皮质激素（ICS）-福莫特罗，作为其阶梯式治疗方案第2步中维持使用ICS加短效β受体激动剂（SABA）缓解药物的替代方案。我们的目的是评估这两种治疗方案的疗效和安全性，重点是预防严重加重。
我们对所有比较按需使用ICS-福莫特罗与维持使用ICS加SABA的随机对照试验（RCT）进行了系统评价和荟萃分析。检索了MEDLINE、Embase、Cochrane对照试验中央注册库和Clinicaltrials.gov，检索时间从各数据库建库至2019年12月12日。主要结局是首次严重加重的时间。如果RCT将按需使用布地奈德-福莫特罗作为维持和缓解方案的一部分，或未报告严重加重情况，则将其排除。该评价已在国际前瞻性系统评价注册库（PROSPERO）注册（注册号CRD42020154680）。
分析纳入了4项RCT（n = 8065名参与者）。按需使用ICS-福莫特罗与首次严重加重时间延长相关（风险比0.85，95%CI 0.73 - 1.00；p = 0.048），且每日ICS剂量降低（平均差值 -177.3 μg，95%CI -182.2 - -172.4 μg）。按需使用组的哮喘症状控制较差（哮喘控制问卷-5平均差值0.12，95%CI 0.09 - 0.14），尽管这未达到最小临床重要差异0.50分。严重不良事件无显著差异（比值比1.07，95%CI 0.84 - 1.36）。
按需使用ICS-福莫特罗为哮喘患者维持使用低剂量ICS加SABA提供了一种治疗替代方案，当预防严重加重是治疗的主要目标时，可能是首选方案。
