December 9, 2022

Budesonide-Formoterol Maintenance/reliever treatment for poorly controlled asthma

In patients with poorly controlled asthma, use of inhaled corticosteroid (ICS) plus formoterol as maintenance and reliever therapy (SMART) has been 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 stages 3, 4 and 5: 1) SMART; or 2) maintenance ICS – long-acting β2-agonist (LABA) plus short-acting β2-agonist (SABA). In this study, researchers sought to assess the time to first severe asthma exacerbation in patients with poorly controlled asthma who were on SMART compared to patients who were using conventional ICS-LABA maintenance therapy at a high dose. equal or greater plus SABA or formoterol analgesic as needed.

Study investigators searched the literature and internal study databases of 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 previous systematic review and meta-analysis. on the SMART diet.

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

Data from 4863 patients were included in the analysis. The mean age of the participants was 39.8 ± 16.3 years; 62.4% of patients were women. Transition of 1950 participants with uncontrolled asthma from GINA Stage 3 to SMART to Stage 3 or Stage 4 was associated with a prolonged time to development of the first severe asthma exacerbation , with a 29% reduced risk compared to ICS-LABA plus SABA maintenance stage 4 (risk ratio [HR], 0.71; 95% CI, 0.52-0.97).

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

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

The researchers said their results suggest that if an adult or adolescent patient receiving GINA Stage 3 or 4 treatment has poorly controlled asthma, it is better to transition that individual to the SMART diet, rather than intensify or continue the GINA. treatment step with ICS-LABA maintenance plus SABA rescue treatment.

Disclosure: Some of the study authors have disclosed affiliations with biotechnology, pharmaceutical and/or device companies. Please see the original citation for a full list of author disclosures.


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