Differences in the effectiveness of single, dual, and triple inhaled corticosteroid therapy for reducing future risk of severe asthma exacerbation: A systematic review and network meta-analysis.

IMPORTANCE

The effectiveness of different combinations of inhaled corticosteroid (ICS) therapies in reducing severe exacerbations of adult asthma remains unclear.

OBJECTIVE

This network meta-analysis (NMA) extensively evaluated the treatment effects of single ICS; dual ICS i.e., ICS/long-acting β2-adrenergic agonists (LABA); ICS/LABA as single maintenance and reliever therapy (SMART); and triple ICS, i.e., ICS/LABA/long-acting muscarinic antagonists (LAMA) in preventing severe asthma exacerbations.

DATA SOURCES

A systematic search of English databases, including PubMed and Web of Science, was conducted until December 31, 2022, using PRISMA-NMA.

STUDY SELECTION

Using the PICOS criteria, the questions for this study were carefully selected so that the correct keywords could be identified.

DATA EXTRACTION AND SYNTHESIS

A pairwise meta-analysis was used to select trials based on the criteria for minimizing heterogeneity (I). Subsequently, the "BUGSnet" package of R software was used to perform a Bayesian network meta-analysis.

MAIN OUTCOME MEASURES

The main outcome measures were risk rate and annualized rate ratio of severe asthma exacerbations.

RESULTS

This review included 56 randomized control trials (RCTs; n = 78,171 patients). As the pairwise meta-analysis demonstrated that the annualized rate ratio of severe asthma exacerbation had moderate heterogeneity, we analyzed the risk rate of severe asthma exacerbation using a network meta-analysis. In terms of direct/indirect comparisons with non-ICS, single ICS, dual ICS, SMART, and triple ICS reduced severe asthma exacerbations by 34 %, 47 %, 58 %, and 57 %, respectively. SMART and triple ICS showed high effectiveness in reducing severe exacerbations.

CONCLUSION

AND RELEVANCE: SMART and triple ICS were ranked higher in effectiveness in reducing severe asthma exacerbations in comparison with other therapies, indicating that these are the most effective treatments for reducing the future risk of severe asthma exacerbations.