Comparative effectiveness of azithromycin versus roflumilast in patients with chronic obstructive pulmonary disease: emulated target trial.

Abstract (English)

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 <u>></u>40 years with active COPD and at least 183 days of continuous insurance enrolment who initiated a new oral prescription for maintenance azithromycin or roflumilast. Those with evidence of other pulmonary conditions or alternative indications for azithromycin were excluded. Propensity score matching was used between treatment groups. 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 https://osf.io/95d2v.