Benefit-harm analysis of azithromycin for the prevention of acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Low-dose oral azithromycin therapy is recommended as a preventive treatment for acute exacerbations of COPD. However, the overall benefit-harm balance of this treatment has not been well studied. METHODS: A probabilistic Markov model of COPD was created to simulate the course of COPD over 20 years. The model was populated with evidence from the literature and dedicated data analysis. The benefit of azithromycin was modelled as a reduction in exacerbation rates. Adverse events, including cardiovascular events, hearing loss, gastrointestinal symptoms and antimicrobial resistance (leading to a gradual decline in the effectiveness of azithromycin), were considered. All outcomes were assigned a health-related utility weight to estimate the overall net change in the quality-adjusted life year (QALY) associated with the use of azithromycin. RESULTS: In patients with a positive exacerbation history, azithromycin resulted in a net QALY gain of 17.9 per 100 patients (99.8% probability of expected QALY gain) over 20 years. The net benefit increased to 21.8 QALYs per 100 patients (99.9% probability of expected QALY gain) among the 'frequent exacerbator' subgroup. Azithromycin was not net beneficial among those without any moderate/severe exacerbations in the previous year. Findings were robust against series of sensitivity, scenario and threshold analyses. CONCLUSIONS: Long-term therapy with azithromycin confers a net benefit to ex-smoker patients with COPD with a recent history of exacerbations and an even larger benefit to those who are frequent exacerbators.

A Cost-Effectiveness Analysis of Azithromycin for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Rationale: Daily oral azithromycin therapy can reduce the risk of acute exacerbations of chronic obstructive pulmonary disease (COPD). However, given its adverse events and additional costs, it is not known whether adding long-term azithromycin as an adjunct therapy to inhaled pharmacotherapy is cost effective. Objectives: The objective of this study was to evaluate the cost-effectiveness of add-on azithromycin therapy in COPD as recommended by contemporary COPD management guidelines. Methods: We extended a previously validated Canadian COPD policy model to include azithromycin-related inputs and outcomes. The cost-effectiveness of azithromycin was evaluated over a 20-year time horizon in patients who continue to exacerbate despite receiving maximal inhaled therapies. The benefit of azithromycin was modeled as a reduction in exacerbation rates. Adverse events included cardiovascular death, hearing loss, gastrointestinal symptoms, and antimicrobial resistance. The incremental cost-effectiveness ratio (ICER) was calculated with costs in 2020 Canadian dollars ($) and quality-adjusted life-years (QALYs) discounted at 1.5% per year. The analysis was stratified among patient subgroups based on exacerbation histories. Results: In patients with a positive exacerbation history (one or more events in the previous 12 mo), azithromycin was associated with $49,732 costs, 7.65 QALYs, and 10.95 exacerbations per patient over 20 years. The corresponding values were $48,436, 7.62, and 11.86 for the reference group, resulting in an ICER of $43,200 per QALY gained. In patients defined as frequent exacerbators (two or more moderate or one or more severe events in the past 12 mo), the ICER was reduced to $8,862 per QALY gained. In patients with no history of exacerbation, azithromycin had lower QALYs and higher costs than the reference group. Conclusions: Add-on azithromycin is cost effective in patients with a recent history of exacerbations at commonly accepted willingness-to-pay thresholds of $50,000-$100,000/QALY. Guidelines should consider recommending add-on azithromycin for patients who had at least one moderate or severe exacerbation in the past year, albeit more information about treatment efficacy would strengthen this recommendation.