Long-term azithromycin confers a net benefit in COPD patients who are former smokers with a recent history of exacerbations, a model-based benefit-harm analysis has shown.

The benefit is likely to be larger in those patients who suffer frequent exacerbations, the study found.

The investigators created a probabilistic model-based benefit-harm analysis of prophylactic azithromycin (250 mg/day) to prevent COPD exacerbations among patients already on maximum inhaled therapy. This simulated the course of COPD over 20 years. Benefits and harms were translated into quality of life weights to generate a single metric of net changes in quality-adjusted life years (QALYs).

The study population was derived from a large randomised controlled trial of azithromycin in COPD (the MACRO study). Patients with GOLD severity grades II to IV were considered who met exacerbation criteria.

Data from other studies were used to model expected transition from one GOLD grade to the next, background mortality was calculated from national statistics. Annual rates of exacerbations were modelled as a function of the underlying GOLD grades.

A literature scoping exercise was undertaken looking at the adverse effects of azithromycin which could potentially affect its net benefit.

The model examined the effect of the drug on the decline in GOLD stage, the prevalence of adverse events and the increase in antibiotic resistance over time. QALYs were calculated for each model state and the net QALY gain determined from the use of azithromycin. The benefit: harm ratio from different histories of exacerbations was also investigated.

In the primary target population (i.e. patients with GOLD grade ≥ ll with at least one moderate/severe exacerbation in the past 12 months) azithromycin resulted in a net QALY gain of 17.9 per 100 patients (99.8% probability of expected QALY gain) over 20 years.

There was a higher net QALY gain in those with more frequent exacerbations (two or more moderate or at least one severe exacerbation in the previous year) of 21.8 QALYs per 100 patients (99.9% probability of expected QALY gain) over 20 years.

There was no benefit in patients who had not had a moderate or severe exacerbation in the previous year.

The authors conclude that:

‘This study shows that azithromycin is very likely to be net beneficial in patients with COPD with a positive history of exacerbations.’

‘Future research should evaluate the effectiveness of azithromycin in current smokers,’ they add.

The NICE guideline on COPD recommends consideration of prophylactic oral azithromycin where there are troublesome exacerbations, when inhaled therapy has been optimised and the patient is a nonsmoker.¹ These findings support current NICE guidance.

Dr Peter Saul