Asthma

Macrolides ‘probably’ linked with a reduction in severe asthma exacerbations: Cochrane


Macrolides are linked with a moderate reduction in asthma exacerbations requiring hospitalisations compared to placebo, but the evidence is of low-quality, concludes a Cochrane review.

The research team undertook a review of 25 eligible randomised controlled trials in the Cochrane Airways Group Specialised Register to explore the effects of macrolide antibiotics versus placebo for managing chronic asthma.

The trials involved 1,973 participants – mostly adults aged 21 to 61 years – who received a macrolide or placebo for at least four weeks. The researchers highlighted that all participants were recruited in outpatient settings, with “highly variable” inclusion criteria, interventions and outcomes.

The findings, published in the Cochrane Library, suggest that “macrolides probably deliver a moderately sized reduction in exacerbations requiring hospitalisations compared to placebo (odds ratio (OR) 0.47)”, based on moderately‐certain evidence.

The class of drug also probably cuts the number of exacerbations requiring emergency department visits and/or treatment with systemic steroids (based on moderate‐certainty evidence), and might reduce symptoms (as measured on symptom scales; standardised mean difference (SMD) −0.46, based on very low-certainty evidence).

The research indicates that macrolides may result in a little improvement in ACQ (SMD −0.17, low‐certainty evidence), but could have “little to no effect on AQLQ” (mean difference (MD) 0.24, very low‐certainty evidence).

According to the researchers, the review “highlights the need for researchers to report outcomes accurately and according to standard definitions”.

Also, future trials could evaluate whether the effect of macrolide on reducing exacerbations is “sustained across all the severe asthma phenotypes, the comparison with newer biological drugs, whether effects persist or wane after treatment cessation and whether effects are associated with infection biomarkers”.
The current Australian Asthma Handbook guidelines for management of asthma states that the decision about whether or not to use antibiotics for treatment of respiratory tract infections in people with asthma should be made on the same basis as in people without asthma.

“Long-term therapy with macrolides may have an anti-inflammatory effect, but there is not enough evidence to recommend this routinely for managing asthma.” they advise

However some Australian respiratory physicians and recent GINA (Global Initiative for Asthma) guidelines have recommended that in selected patients it may be appropriate to consider a modified n-of-1 trial of add-on therapies such as low dose macrolide antibiotics.

Pragmatic guidelines from the British Thoracic Society addressing the long-term use of macrolides stress that pharmacological and non-pharmacological conventional therapies should be optimised before they are considered for any respiratory disease.

Based on evidence from the AMAZES and AZIZAST trials a conditional recommendation is given for macrolides in adults with asthma symptoms despite 80% adherence to high-dose inhaled steroids (>800 μg/day) and at least one exacerbation requiring steroids in the past year.

However, the guidelines state there is strong evidence to suggest that macrolide therapy should not be used as a way to reduce oral steroid doses in this group of patients.

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