Comparative effectiveness of azithromycin versus roflumilast in patients with chronic obstructive pulmonary disease: emulated target trial
Gerard T Portela, Shirley V Wang, Samy Suissa, Sebastian Schneeweiss, William B FeldmanAbstract
Objective
To compare the risk of moderate or severe exacerbations of chronic obstructive pulmonary disease (COPD) among new users of azithromycin versus roflumilast in a population of patients with active COPD treated in routine clinical practice.
Design
Target trial emulation.
Data source
Optum Clinformatics Data Mart Database from 1 March 2011 to 31 August 2024.
Participants
Patients aged
Main outcome measures
The primary outcome was time to first moderate or severe COPD exacerbation. Cox proportional hazards models estimated hazard ratios.
Results
A total of 7550 matched pairs of patients initiating azithromycin versus roflumilast were included in the cohort. The mean age of patients was 70 years, and 56% were women. The unadjusted incidence of a first moderate or severe COPD exacerbation among patients in the cohort receiving azithromycin or roflumilast was 1.2 per person year. Compared with roflumilast, azithromycin was associated with a 17% reduction in the hazard of first moderate or severe COPD exacerbation (hazard ratio 0.83, 95% confidence interval (CI) 0.79 to 0.87; number needed to treat 15, 95% CI 12 to 21). These results were robust across a range of prespecified sensitivity and subgroup analyses.
Conclusions
Among patients with active COPD, azithromycin use was associated with a reduced likelihood of moderate or severe COPD exacerbations compared with roflumilast use. Although this study did not assess the comparative safety of these agents, it provides evidence on treatment outcomes that may complement forthcoming data from a large randomised controlled trial.
Study registration
Centre for Open Science Real-World Evidence Registry