Rayner DG, Ferri DM, Guyatt GH, O’Byrne PM, et al. JAMA. 2024 Oct 28. doi: 10.1001/jama.2024.22700.
Key Points
Question In people with asthma, compared with short-acting β agonists (SABA) alone, is the combination of SABA with inhaled corticosteroids (ICS-SABA) and the combination of formoterol with inhaled corticosteroids (ICS-formoterol) associated with better asthma outcomes?
Findings In this systematic review and network meta-analysis that included 27 randomized clinical trials (50 496 adult and pediatric patients), compared with SABA alone, ICS-SABA was associated with a 4.7% reduction in risk of severe exacerbations and ICS-formoterol was associated with a 10.3% reduction in severe exacerbations, without an increase in adverse events.
Meaning Both combined ICS with SABA and ICS with formoterol were associated with lower risks of severe asthma exacerbations compared with SABA alone.
Abstract
Importance The optimal inhaled reliever therapy for asthma remains unclear.
Objective To compare short-acting β agonists (SABA) alone with SABA combined with inhaled corticosteroids (ICS) and with the fast-onset, long-acting β agonist formoterol combined with ICS for asthma.
Data Sources The MEDLINE, Embase, and CENTRAL databases were searched from January 1, 2020, to September 27, 2024, without language restrictions.
Study Selection Pairs of reviewers independently selected randomized clinical trials evaluating (1) SABA alone, (2) ICS with formoterol, and (3) ICS with SABA (combined or separate inhalers).
Data Extraction and Synthesis Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses synthesized outcomes. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to evaluate the certainty of evidence.
Main Outcomes and Measures Asthma symptom control (5-item Asthma Control Questionnaire; range, 0-6, lower scores indicate better asthma control; minimum important difference [MID], 0.5 points), asthma-related quality of life (Asthma Quality of Life Questionnaire; range, 1-7, higher scores indicate better quality of life; MID, 0.5 points), risk of severe exacerbations, and risk of serious adverse events.
Results A total of 27 randomized clinical trials (N = 50 496 adult and pediatric patients; mean age, 41.0 years; 20 288 male [40%]) were included. Compared with SABA alone, both ICS-containing relievers were associated with fewer severe exacerbations (ICS-formoterol risk ratio [RR], 0.65 [95% CI, 0.60-0.72]; risk difference [RD], −10.3% [95% CI, −11.8% to −8.3%]; ICS-SABA RR, 0.84 [95% CI, 0.73-0.95]; RD, −4.7% [95% CI, −8.0% to −1.5%]) with high certainty. Compared with SABA alone, both ICS-containing relievers were associated with improved asthma control (ICS-formoterol RR improvement [MID] in total score, 1.07 [95% CI, 1.04-1.10]; RD, 4.1% [95% CI, 2.3%-5.9%]; ICS-SABA RR, 1.09 [95% CI, 1.03-1.15]; RD, 5.4% [95% CI, 1.8%-8.5%]) with high certainty. In an indirect comparison with ICS-SABA, ICS-formoterol was associated with fewer severe exacerbations (RR, 0.78 [95% CI, 0.66-0.92]; RD, −5.5% [95% CI, −8.4% to −2.0%]) with moderate certainty. Compared with SABA alone, ICS-formoterol (RD, −0.6% [95% CI, −1.3% to 0%]) was not associated with increased risk of serious adverse events (high certainty) and ICS-SABA (RD, 0% [95% CI, −1.1% to 1.2%]) was not associated with increased risk of serious adverse events (moderate certainty).
Conclusions and Relevance In this network meta-analysis of patients with asthma, ICS combined with formoterol and ICS combined with SABA were each associated with reduced asthma exacerbations and improved asthma control compared with SABA alone.