Macrolides reduce exacerbations, improve quality of life in asthma treatment
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Key takeaways:
- The meta-analysis included 20 randomized control trials with 2,067 participants.
- Patients who used macrolides were 61% more likely to achieve a 0.5-point improvement in Asthma Control Questionnaire-6 scores.
BOSTON — Macrolides likely reduce severe exacerbations and improve quality of life and asthma control among patients with asthma, according to a presentation at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.
Also, macrolides present relatively low risks for severe adverse events, discontinuation because of adverse events, or mortality, Leonard B. Bacharier, MD, FACAAI, FAAAAI, said during his presentation.
“We’ve seen that low-lose macrolides, most typically azithromycin, have been commonly considered as an adjunct therapy in severe asthma that is refractory to our standard approach,” Bacharier, Janie Robinson and John Moore Lee Chair in Pediatrics at Vanderbilt University Medical Center, said.
“Our existing guidance, however, for asthma management does not consider all the available evidence for macrolides, despite what we believe is relatively frequent use in severe asthma,” he continued.
Multiple trials have been published since the last systematic review of the use of macrolides in severe asthma, Bacharier noted.
“We thought that this was really a critical question for our colleagues,” said Bacharier, who also is a member of the AAAAI/ACAAI Joint Task Force on Practice Parameters Severe and Difficult-to-Control Asthma Guideline Development Group.
The group conducted a systematic meta-analysis that included all randomized control trials of patients with asthma who received any macrolide vs. a non-macrolide comparator.
“Our outcomes for all of these meta-analyses were really pretty similar — severe exacerbations, measures of asthma control, asthma-related quality of life, serious adverse events, discontinuation due to adverse events and, where we could assess it, mortality,” Bacharier said.
The classic Bayesian meta-analysis was conducted per Cochrane and Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) guidance, Bacharier said, using GRADE to evaluate the certainty or quality of the evidence.
“This allows us to not just use the numbers, but to up- or downgrade those, the confidence in those findings, based on our assessment for the risks of bias, of inconsistency across studies, of imprecision, or indirect effects, and of publication bias,” Bacharier said.
The review included 20 randomized controlled trials published between 2021 and August 2024 with a median duration of 12 weeks (range, 4-104 weeks). The 2,067 participants in these trials had a median age of 42 years (range, 10-61 years) and were 52% female.
“We looked at everything that is a macrolide in the literature,” Bacharier said.
Ten trials investigated azithromycin, four investigated roxithromycin, four included clarithromycin and two included troleandomycin.
When macrolides were added to treatment, rates of moderate to severe exacerbations fell by 28% (incidence rate ratio = 0.72; 95% CI, 0.61-0.84) vs. the comparator.
In terms of annualized absolute effects, patients who did not use macrolides experienced 0.55 events per patient-year, and those who did use them experienced 0.4 events per patient-year for a difference of 0.16 events per patient year (95% CI, 0.22-0.09).
Specifically, among patients on Global Initiative for Asthma step 5, annualized absolute effects included 0.46 moderate to severe exacerbations per patient-year for those who did not use macrolides and 0.33 moderate to severe exacerbations per patient-year for those who did use them for a difference of 0.13 events per patient-year (95% CI, 0.18-0.07).
“There was a reduction in severe exacerbations,” Bacharier said. “We felt that this evidence was pretty strong and graded this certainty of evidence as moderate.”
Macrolide therapy also improved asthma control, with high levels of certainty, he continued. The weighted mean difference between the two groups in Asthma Control Questionnaire 6 (ACQ-6) scores was –0.23 (95% CI, –0.36 to –0.11).
The risk ratio for improving by a minimally important difference (MID) of 0.5 points on the ACQ-6 was 1.61 (95% CI, 1.27-1.99). The risk difference for improving by a MID of 0.5 points on the ACQ-6 was 16% more (95% CI, 7%-25% more).
“We felt, really as strongly as we could, that these data were robust and showed an improvement in asthma control,” Bacharier said.
The weighted mean difference in Asthma Quality of Life Questionnaire (AQLQ) scores between those who were and who were not on macrolides was 0.18 (95% CI, 0-0.36). The risk ratio for improving by a MID of 0.5 points on the AQLQ was 1.16 (95% CI, 1-1.33), with a risk difference for improving by a MID of 0.5 points of 7% more (95% CI, 0%-14% more).
“When we looked at quality of life, the evidence was a little less strong, so we graded it as moderate,” Bacharier said.
Patients who used macrolides also had two fewer serious adverse events per 1,000 (95% CI, 5 fewer to 2 more). The risk difference for discontinuation of treatment due to an adverse event was one fewer per 1,000 (95% CI, 4 fewer to 2 more). The risk difference for mortality was one fewer per 1,000 (95% CI, 4 fewer to 2 more).
Bacharier said these “encouraging” findings were based on moderately certain evidence as well.
“We can summarize these macrolide effects as saying that they likely reduce severe exacerbations with moderate certainty, improve asthma control with high certainty, and likely improve asthma-related quality of life with moderate certainty,” he said.
These findings also indicate with moderate certainty that macrolides likely do not increase serious and adverse events, discontinuations due to serious or other adverse events or mortality, he continued.
“That’s our assessment of where the macrolides are,” he said. “It’s a very reassuring place, and I think we have a pretty good idea of how these are going to get incorporated into the practice parameters.”