A comprehensive meta-analysis published in JAMA Network Open has found that inhaled corticosteroids (ICS) combined with either formoterol or short-acting beta-agonists (SABA) significantly reduce the risk of severe asthma exacerbations compared to using SABA alone. The study, which included data from over 50,000 adult and pediatric patients across 27 randomized clinical trials (RCTs), highlights the potential benefits of incorporating ICS into reliever therapies for asthma management.
The research team systematically searched MEDLINE, Embase, and CENTRAL databases from January 1, 2020, to September 27, 2024, to identify relevant RCTs. The analysis focused on comparing SABA alone with ICS combined with formoterol (ICS-formoterol) and ICS combined with SABA (ICS-SABA) in terms of asthma outcomes.
Key Findings on Exacerbations
The meta-analysis revealed that ICS-formoterol was associated with a 10.3% reduction in severe exacerbations (Risk Ratio [RR], 0.65; 95% CI, 0.60-0.72), while ICS-SABA was linked to a 4.7% reduction (RR, 0.84; 95% CI, 0.73-0.95). These findings were categorized as high-certainty evidence, indicating a robust and reliable effect.
Impact on Asthma Control and Quality of Life
Both ICS-formoterol and ICS-SABA were also associated with improved asthma control compared to SABA alone. Specifically, ICS-formoterol showed a 4.1% improvement (RR, 1.07; 95% CI, 1.04-1.10), and ICS-SABA demonstrated a 5.4% improvement (RR, 1.09; 95% CI, 1.03-1.15). However, the researchers noted that these effect sizes were small and may not be clinically significant for all patients.
Safety Profile
Importantly, the study found no increased risk of serious adverse events with either ICS-formoterol or ICS-SABA compared to SABA alone. This suggests that incorporating ICS into reliever therapies does not compromise patient safety.
Expert Commentary
"These findings support the use of ICS-containing relievers as a preferred strategy over SABA alone for managing asthma symptoms and reducing exacerbation risk," said Dr. Derek K. Chu, the corresponding author of the study from McMaster University. "However, clinicians should consider individual patient needs and preferences when selecting the most appropriate reliever therapy."
Implications for Clinical Practice
The results of this meta-analysis have significant implications for clinical practice, potentially influencing guideline recommendations and treatment strategies for asthma. While current guidelines from organizations like the Global Initiative for Asthma (GINA) already favor ICS-formoterol, the FDA's recent approval of ICS-SABA as a reliever inhaler adds another option for clinicians to consider.
Study Limitations
The authors acknowledge several limitations, including the lack of head-to-head trials directly comparing ICS-formoterol and ICS-SABA. Additionally, the analysis included only a small number of trials focused exclusively on pediatric populations. Further research is needed to address these gaps and provide more definitive guidance on the optimal reliever therapy for different patient subgroups.
Conclusion
Overall, this meta-analysis provides strong evidence supporting the use of ICS-containing relievers as a superior alternative to SABA alone in asthma management. By reducing exacerbations and improving symptom control without increasing adverse events, ICS-formoterol and ICS-SABA offer valuable options for patients seeking effective and safe relief from asthma symptoms.
