BACKGROUND: The benefits and harms of using macrolides for asthma remain unclear.
OBJECTIVE: As part of upcoming Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters guidelines addressing severe asthma, we systematically reviewed the efficacy and safety of macrolides for asthma.
METHODS: We systematically searched MEDLINE, Embase, and CENTRAL to April 12, 2025, for randomized trials comparing macrolides with placebo or standard care for asthma. Paired reviewers independently screened records and extracted data. Individual patient-level data in random effects analysis of covariance models addressed asthma control and asthma-related quality of life. Random effects meta-analyses addressed severe exacerbations and harms. We used the Grading of Recommendations Assessment, Development and Evaluation approach to evaluate certainty of evidence. Our study protocol is registered in PROSPERO (CRD42023408677).
RESULTS: Our meta-analysis comprised 19 trials enrolling 1825 participants. Compared with placebo, macrolides improve asthma control (6-item Asthma Control Questionnaire; score range 0-6, lower better; between-group mean difference: -0.23 [95% CI -0.32 to -0.13]; 40.6% vs 21.6% improving by minimally important difference of 0.5 point; high certainty), likely reduce severe exacerbations (incidence rate ratio: 0.75 [95% CI 0.57 to 0.98]; rate difference: 0.26 fewer events per patient-year [95% CI 0.45 to 0.02 fewer events]; moderate certainty), and likely modestly improve quality of life (Asthma Quality of Life Questionnaire; score range 1-7, higher better; mean difference: 0.11 [95% CI -0.06 to 0.29]; 47.6% vs 42.4% improving by minimally important difference of 0.5 points; moderate certainty) with little to no effect on serious adverse events and mortality (high certainty). Relative effects were similar among patients with type 2 high inflammation versus type 2 low inflammation asthma.
CONCLUSIONS: Macrolides likely reduce severe exacerbations and improve asthma control and quality of life with little to no difference in serious harms among patients with type 2 high inflammation or type 2 low inflammation asthma.
| Discipline Area | Score |
|---|---|
| Family Medicine (FM)/General Practice (GP) |  |
| General Internal Medicine-Primary Care(US) | |
| Pediatrics (General) | |
| Allergy and Immunology | Coming Soon... |
| Respirology/Pulmonology | Coming Soon... |
The effect size of the intervention was not large, and most participants had moderate or severe asthma. This suggests a role for macrolides as a second-line therapy for moderately severe asthma that is not well controlled with standard therapies.
It will good to assess the relevance of it once we see the guideline statements.
As a pediatrician, I am uncertain about the relevance of this issue to my routine clinical practice, particularly given that the discussion concerns long-term (12-26 wks in 3 pediatric studies) macrolide use.
This systematic review of RCTs found that macrolides reduce asthma exacerbations and improve asthma control. Many of the individual trials found significant differences on their own, and the review includes only 2 new trials done in the past decade. Most clinicians likely know this already.