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UBC Theses and Dissertations

A benefit-harm and cost-effectiveness analysis of azithromycin for the prevention of acute exacerbations of chronic obstructive pulmonary disease Ahmadian Hosseini, Safa Sadat


Low-dose oral azithromycin therapy is recommended as a preventive treatment for acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD). However, its role in the treatment of COPD remains controversial owing to its side effects. I determined the overall benefit- harm balance as well as the cost-effectiveness of using long-term azithromycin as an add-on to maximal inhaled therapy in the management of patients with COPD, compared with maximal inhaled therapy alone. To evaluate the benefit-harm of azithromycin, I created a probabilistic Markov model of COPD to simulate the course of COPD over 20 years. For assessing the cost-effectiveness, I extended a previously validated health economics model of COPD for Canada to include azithromycin-related outcomes. In both studies, 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 years (QALY) associated with the use of azithromycin. The incremental cost-effectiveness ratio (ICER) was defined as the incremental costs (in 2020 Canadian dollars) per QALY gained, and per exacerbation avoided, with costs and health outcomes discounted at 1.5% per year. All outcomes were calculated among subgroups with different exacerbation histories. In the first study, among patients with a positive exacerbation history, azithromycin resulted in a net QALY gain of 17.9 per 100 patients (99.8% probability of positive expected QALY gain) over 20 years. The net benefit increased to 21.8 QALYs per 100 patients (99.9% probability of positive expected QALY gain) among the ‘frequent exacerbators’. In the second study, the ICER was $16,850 per QALY gained for treatment with azithromycin among patients with a positive exacerbation history. The ICER decreased to $8,544 per person over 20 years among the ‘frequent exacerbator’ subgroup. Azithromycin had an ICER greater than $100,000 per QALY gained among those without any moderate/severe exacerbations in the previous year. Findings were robust against a series of sensitivity, scenario, and threshold analyses.

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