“Macrolides in Asthma and COPD” presented by Prof. Peter Gibson

Prof. Peter Gibson presented “Macrolides in Asthma and COPD” in May, 2018.

Presentation Summary:

Prof. Gibson presents an overview of the effects of macrolide treatment, as an add-on therapy for asthma and COPD.

Macrolides (e.g. erythromycin and azithromycin) are antibiotic molecules, which also have anti-inflammatory effects. Macrolide treatment improves health outcomes in a range of obstructive airways diseases and is being assessed as a treatment option for asthma and COPD.

In asthma and COPD, the primary effect of long-term macrolide treatment is a reduction in exacerbations. Side effects of macrolide treatment should be considered prior to treatment and monitored/managed during treatment.

Prof. Gibson presents evidence that azithromycin treatment reduces exacerbations in adults with obstructive airways disease (asthma or COPD) with ongoing symptoms and exacerbations despite treatment with long-acting bronchodilators and inhaled corticosteroids (ICS), if indicated. Patients should be screened prior to treatment, to confirm no QTc prolongation, cardiac arrhythmia or hearing loss. Treatment dose is 500mg, 3 times per week (or 250mg daily) for up to 12 months.

Key Points:

• Erythromycin is a naturally occurring antibiotic compound, which has been modified to generate the synthetic macrolide antibiotics clarithromycin and azithromycin
• Macrolide treatment improves outcomes in a range of obstructive airways diseases, including cystic fibrosis and non-CF bronchiectasis
• A role for macrolides in the treatment of COPD and asthma is under assessment
• Primary effect of macrolide treatment is reduced exacerbations, rather than effects on lung function or quality-of-life measures
• Variable results have been observed of macrolide treatment on the severity of “acute exacerbations” and limited evidence is available of effects on “protracted exacerbations”
• Treatment efficacy is primarily observed on exacerbation frequency over multiple years
• A systematic review of macrolide efficacy in COPD demonstrated a 42% reduction in exacerbation rate (Ni et al. 2015. PLoS ONE)
• Two studies have assessed the effect of macrolide (azithromycin) treatment for asthma
• In the first study (AZISAST trial), azithromycin treatment reduced exacerbations only in a population of patients with “non-eosinophilic asthma” defined by low fractional exhaled nitric oxide (FeNO; Brusselle et al. 2013. Thorax)
• In the 2^nd study (AMAZES trial), azithromycin treatment reduced exacerbation rates by 40%, for all patient subgroups assessed (Gibson et al. 2017. Lancet)
• Important side effects of macrolide treatment to consider include hearing loss at high doses, hepatitic toxicity, diarrhoea and QT prolongation. Patient pre-screening for the AMAZES trial excluded patients with QTc >480msec. When relevant, it is useful to change statin prescriptions to rosuvastatin prior to azithromycin treatment to limit risk of rhabdomyolysis (Gibson et al. 2017. Lancet)
• Safety assessments in the AMAZES trial documented adverse events, infections and the emergence of antibiotic resistance. Infections were reduced by azithromycin treatment. Rates of diarrhoea were increased following macrolide treatment and managed by modulating treatment dose. Observed rates of pathogen antibiotic resistance were increased following treatment, which was not statistically significant but may be clinically relevant (Gibson et al. 2017. Lancet)
• A year of azithromycin treatment is effective for asthma and COPD, with some side effects which can be effectively managed
• Regarding choice of macrolide antibiotics: azithromycin has an increased half-life, and fewer symptom side effects, compared to erythromycin. Efficacy outcomes are similar for azithromycin vs. erythromycin in COPD trials (Ni et al. 2015. PLoS ONE) and no erythromycin RCTs are available for asthma
• Regarding duration of treatment: macrolide treatment for less than 3 months failed to demonstrate efficacy in COPD trials. Similarly, in asthma RCTs, differences in exacerbation rate only became apparent after 3-months
• No clear seasonal effects of azithromycin treatment were observed on exacerbation rates in the AMAZES trial

About Prof. Peter Gibson:

Prof. Peter Gibson (University of Newcastle, Hunter Medical Research Institute, John Hunter Hospital) is a respiratory physician and clinical scientist studying the disease mechanisms and treatment of severe asthma, chronic obstructive pulmonary disease (COPD), cough and other airway disorders.

He has over 450 published articles and an extensive track record of research success and mentorship of clinical researchers. He is also the Past President of the Thoracic Society of Australia and New Zealand (2015-6).

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