Effect of Azithromycin on Asthma Remission in Adults With Persistent Uncontrolled Asthma A Secondary Analysis of a Randomized, Double-Anonymized, Placebo-Controlled Trial

BACKGROUND: Asthma remission is a potential treatment goal. RESEARCH QUESTION: Does adding azithromycin to standard therapy in patients with persistent uncontrolled asthma induce remission compared with placebo? STUDY DESIGN AND METHODS: This secondary analysis used data from the Asthma and Macrolides: the Azithromycin Efficacy fi cacy and Safety (AMAZES) clinical trial-a - a doubleanonymized placebo-controlled trial that evaluated the safety and efficacy fi cacy of azithromycin on asthma exacerbations. The primary remission definition fi nition (referred to as clinical remission) was zero exacerbations and zero oral corticosteroids during the previous 6 months evaluated at 12 months and a 5-item Asthma Control Questionnaire score 1 at 12 months. Secondary remission definitions fi nitions included clinical remission plus lung function criteria (postbronchodilator FEV1 1 >= 80% or postbronchodilator FEV1 1 5% decline from baseline) and complete remission (sputum eosinophil count < 3% plus the aforementioned criteria). Sensitivity analyses explored the robustness of primary and secondary remission definitions. fi nitions. The predictors of clinical remission were identified. fi ed. RESULTS: A total of 335 participants (41.5% male; median age, 61.01 years; quartile 1-3, 51.03-68.73) who completed the 12-month treatment period were included in the analysis. Twelve months of treatment with azithromycin induced asthma remission in a subgroup of patients, and a significantly fi cantly higher proportion in the azithromycin arm achieved both clinical remission (50.6% vs 38.9%; P = .032) and clinical remission plus lung function criteria (50.8% vs 37.1%; P = .029) compared with placebo, respectively. In addition, a higher proportion of the azithromycin group achieved complete remission (23% vs 13.7%; P = .058). Sensitivity analyses supported these fi ndings. Baseline factors (eg, better asthma-related quality of life, absence of oral corticosteroid burst in the previous year) predicted the odds of achieving clinical remission. Azithromycin induced remission in both eosinophilic and noneosinophilic asthma. INTERPRETATION: In this study, adults with persistent symptomatic asthma achieved a higher remission rate when treated with azithromycin. Remission on treatment may be an achievable treatment target in moderate/severe asthma, and future studies should consider remission as an outcome measure. CHEST 2024; 166(2):262-270