In patients with poorly controlled asthma, use of the single-inhaler combination inhaled corticosteroid (ICS)-formoterol as both maintenance and reliever treatment (SMART) was associated with a longer time to first severe asthma exacerbation compared with alternative therapies recommended by the Global Initiative for Asthma (GINA), according to results of a meta-analysis and systematic review published in JAMA Network Open.   

GINA recommends 2 ICS-LABA treatment regimens for patients at treatment steps 3, 4, and 5: 1) SMART; or 2) maintenance ICS–long-acting β2-agonist (LABA) plus short-acting β2-agonist (SABA) reliever. In this study, researchers sought to assess the time to the first severe asthma exacerbation in patients with poorly controlled asthma who followed SMART vs patients using an equal or higher dose conventional ICS-LABA maintenance therapy plus as-needed SABA or formoterol reliever. 

Study investigators searched the literature and internal study databases at AstraZeneca and the Medical Research Institute of New Zealand for relevant randomized controlled trials (RCTs) published between January 1990 and February 2018. The researchers also used studies referenced in a prior systematic review and meta-analysis on the SMART regimen. 


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Studies of 24 weeks duration or longer were included in the review if they reported baseline data on GINA treatment step, efficacy measures for severe exacerbations, and asthma control status. Patients included in the chosen studies were adults and adolescents with asthma and baseline Asthma Control Questionnaire 5-item version scores of at least 1.5. Data analysis took place between August 2018 and November 2021. The primary study outcome was the time to first severe exacerbation of asthma associated with each of the treatments, per Cox proportional hazards regression analysis. 

Data for 4863 patients were included in the analysis. The mean participant age was 39.8±16.3 years; 62.4% of the patients were female. Switching 1950 participants with uncontrolled asthma at GINA step 3 to SMART at either step 3 or step 4 was associated with a prolonged time to development of first severe asthma exacerbation, with a 29% reduced risk compared with stepping up to step 4 ICS-LABA maintenance plus SABA reliever (hazard ratio [HR], 0.71; 95% CI, 0.52-0.97). 

For 2913 patients studied who had uncontrolled asthma at GINA step 3 or step 4, switching to the SMART regimen was associated with a prolonged time to initial severe asthma exacerbation and a 30% reduced risk compared with staying at the same treatment step (HR, 0.70; 95% CI, 0.58-0.85).

In citing study limitations, the researchers noted that the analysis was restricted to RCTs of the budesonide-formoterol SMART regimen vs fixed-dose ICS-LABA plus SABA because of the requirement to have access to individual patient data. Although this enhanced the internal validity of the study, it meant that the RCT of beclomethasone-dipropionate-formoterol SMART regimen could not be included in the analysis.

The researchers said their findings suggest that if an adult or adolescent patient who receives treatment at GINA step 3 or step 4 has poorly controlled asthma, it is preferable to switch that individual to the SMART regimen, rather than to step up or to continue the GINA treatment step with maintenance ICS-LABA plus SABA reliever therapy.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.  

Reference   

Beasley R, Harrison T, Peterson S, et al. Evaluation of budesonide-formoterol for maintenance and reliever therapy among patients with poorly controlled asthma: a systematic review and meta-analysis.  JAMA Netw Open. 2022;5(3):e220615. doi:10.1001/jamanetworkopen.2022.0615