全球哮喘倡议(GINA)为接受第3至5步治疗的患者推荐了2种替代疗法:单一吸入器联合吸入皮质类固醇-福莫特罗作为维持和缓解剂(SMART)或吸入皮质类固醇长效β2激动剂作为维持剂加上短效β2激动剂作为缓解剂。
评估在哮喘控制不佳的患者中,与增加或继续GINA治疗步骤并维持吸入性皮质类固醇长效β2激动剂加短效β2激动剂缓解相比,转换为SMART是否与首次重度哮喘加重的时间更长有关。
对于本系统综述和荟萃分析,文学,阿斯利康和新西兰医学研究所的内部研究数据库,本研究检索了之前关于SMART的系统评价和荟萃分析的参考文献,以确定1990年1月至2018年2月发表的随机临床试验,这些试验比较了通过SMART进行布地奈德-福莫特罗与维持吸入性皮质类固醇长效β2激动剂+短效β2激动剂缓解剂.
如果报告GINA治疗步骤的基线数据,则包括至少24周的试验,哮喘控制状态,和严重加重的疗效指标。纳入的患者包括患有哮喘和基线哮喘控制问卷5项版本评分为1.5或更高的成人和青少年。
患者水平的数据通过独立提取来识别,并使用固定效应模型进行分析。数据分析于2018年8月至2021年11月进行。
主要结果是与每种治疗相关的首次严重哮喘发作的时间,采用Cox比例风险回归分析。
总的来说,纳入4863例患者(3034例[62.4%]女性;平均年龄[SD],39.8[16.3]年)。在GINA步骤3(n=1950)将未控制的哮喘患者转换为步骤3或步骤4的SMART与首次严重哮喘加重的时间延长有关。与步骤4吸入性皮质类固醇长效β2-激动剂维持加短效β2-激动剂缓解相比,风险降低29%(危险比,0.71;95%CI,0.52-0.97)。对于第3步和第4步未控制的哮喘患者(n=2913),与保持相同的治疗步骤相比,切换到SMART与第一次严重哮喘加重的时间延长和风险降低30%相关(风险比,0.70;95%CI,0.58-0.85)。
在这篇系统综述和荟萃分析中,对于控制不佳的哮喘患者,与增加或继续GINA步骤并维持吸入性皮质类固醇长效β2激动剂加短效β2激动剂缓解相比,SMART与首次严重哮喘加重的时间更长相关。这些结果表明,如果在GINA步骤3或4接受治疗的成人或青少年哮喘控制不佳,优选改用SMART方案,而不是增加或继续GINA治疗步骤,同时维持吸入性皮质类固醇-长效β2激动剂+短效β2激动剂缓解疗法.
The Global Initiative for Asthma (GINA) recommends 2 alternative treatments for patients receiving treatment at steps 3 to 5: single inhaler combination inhaled corticosteroid-formoterol as both maintenance and reliever (SMART) or inhaled corticosteroid-long-acting β2-agonist as maintenance plus short-acting β2-agonist as reliever.
To assess whether switching to SMART is associated with longer time to first severe asthma exacerbation compared with a step up or continuation of GINA treatment step with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever among patients with poorly controlled asthma.
For this systematic
review and meta-analysis, the literature, internal study databases at AstraZeneca and the Medical Research Institute of New Zealand, and references from a previous systematic
review and meta-analysis on SMART were searched to identify randomized clinical trials published from January 1990 to February 2018, that compared budesonide-formoterol by SMART with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever.
Trials of at least 24 weeks\' duration were included if they reported baseline data on GINA treatment step, asthma control status, and efficacy measures of severe exacerbations. Included patients were adults and adolescents with asthma and baseline Asthma Control Questionnaire 5-item version scores of 1.5 or higher.
Patient-level data were identified by independent extraction, and analyses were performed using a fixed-effect model. Data analysis was performed from August 2018 to November 2021.
The primary outcome was time to first severe asthma exacerbation associated with each treatment, analyzed by Cox proportional hazards regression.
Overall, 4863 patients were included (3034 [62.4%] female; mean [SD] age, 39.8 [16.3] years). Switching patients with uncontrolled asthma at GINA step 3 (n = 1950) to SMART at either step 3 or 4 was associated with a prolonged time to first severe asthma exacerbation, with a 29% reduced risk compared with stepping up to step 4 inhaled corticosteroid-long-acting β2-agonist maintenance plus short-acting β2-agonist reliever (hazard ratio, 0.71; 95% CI, 0.52-0.97). For patients with uncontrolled asthma at step 3 and step 4 (n = 2913), switching to SMART was associated with a prolonged time to first severe asthma exacerbation and a 30% reduced risk compared with remaining at the same treatment step (hazard ratio, 0.70; 95% CI, 0.58-0.85).
In this systematic
review and meta-analysis, for patients with poorly controlled asthma, SMART was associated with longer time to first severe asthma exacerbation compared with a step up or continuation of GINA step with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever. These findings suggest that if an adult or adolescent receiving treatment at GINA step 3 or 4 has poorly controlled asthma, it is preferable to switch to the SMART regimen rather than to step up or continue the GINA treatment step with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever therapy.