PT  - JOURNAL ARTICLE
AU  - Safa Ahmadian
AU  - Don D Sin
AU  - Larry Lynd
AU  - Mark Harrison
AU  - Mohsen Sadatsafavi
TI  - Benefit–harm analysis of azithromycin for the prevention of acute exacerbations of chronic obstructive pulmonary disease
AID  - 10.1136/thoraxjnl-2021-217962
DP  - 2022 Nov 01
TA  - Thorax
PG  - 1079--1087
VI  - 77
IP  - 11
4099  - http://thorax.bmj.com/content/77/11/1079.short
4100  - http://thorax.bmj.com/content/77/11/1079.full
SO  - Thorax2022 Nov 01; 77
AB  - 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.The computer code generating all the results presented in this work is available from https://github.com/safaahmadian/AZT_HarmBenefitAnalysis. One section of the code (the analysis of ECLIPSE data) is based on data that were obtained under license and the data cannot be shared.