Azithromycin use may be associated with a lower risk of a first moderate or severe chronic obstructive pulmonary disease exacerbation compared with roflumilast use.
In a target trial emulation, investigators used the Optum Clinformatics Data Mart Database to identify patients 40 years and odler with active chronic obstructive pulmonary disease (COPD) who newly initiated maintenance azithromycin or roflumilast between March 1, 2011, and August 31, 2024. The patients were required to have at least 183 days of continuous insurance enrollment prior to treatment initiation. Active disease was defined by three outpatient claims or one inpatient claim within 3 years before or up to index date and at least one maintenance inhaler fill. Patients with other pulmonary conditions or alternative indications for azithromycin were excluded.
Moderate exacerbations required 5 to 14 days of oral glucocorticoid treatment, whereas severe exacerbations required COPD-related hospitalization. The primary analysis was as-treated, with follow-up continuing for up to 1 year or until treatment discontinuation or switching, mortality, loss of insurance coverage, or the end of available data.
Among 22,054 eligible patients, 10,725 initiated azithromycin and 11,329 initiated roflumilast. After 1:1 propensity score matching, the analysis included 7,550 pairs, with baseline characteristics were well balanced following matching.
After a median follow-up of 88 days, 3,054 patients receiving azithromycin and 3,503 receiving roflumilast experienced a moderate or severe COPD exacerbation, corresponding to unadjusted incidence rates of 1.1 and 1.3 events per person-year, respectively. Azithromycin was associated with a 17% lower likelihood of a first moderate or severe exacerbation. Model-based 1-year risks were 60% with azithromycin and 67% with roflumilast.
Azithromycin was also associated with a 17% lower risk of a first moderate exacerbation and an 11% lower annual rate of moderate or severe exacerbations. Sensitivity analyses produced estimates similar to the primary analysis. In subgroup analyses, the association differed according to baseline COPD hospitalization status: azithromycin was associated with a lower risk among patients without a baseline COPD hospitalization, whereas the estimated risk was similar between treatments among those with a baseline hospitalization.
Study limitations included the short follow-up and misclassification related to claims data. Residual confounding was also possible because the dataset did not include measures such as dyspnea, imaging findings, microbiological profiles, spirometry, or patient and provider preferences. Safety outcomes were not assessed, and the investigators stated that conclusions about the overall benefit-risk profiles of the treatments remained preliminary.
“These findings highlight differences in treatment effectiveness that may help contextualize clinical decision-making when considered alongside safety evidence and will complement data from the RELIANCE trial,” wrote lead study author Gerard T. Portela, of the Division of Pharmacoepidemiology and Pharmacoeconomics in the Department of Medicine at Brigham and Women’s Hospital, and colleagues.
The study was funded by the National Heart, Lung, and Blood Institute. Full disclosures of the study authors can be found in the study.
Source: The BMJ
