Effect of maintenance macrolide de-escalation during the Australian summer on exacerbations of obstructive airway diseases: a randomised, double-blind, placebo-controlled trial

Why clinicians should know about it

• Picked for Pulmonary and Respiratory Medicine (top studies of the week, 25 October 2026): Non‑inferiority RCT of macrolide de‑escalation in obstructive airway disease

Abstract

BACKGROUND: The optimal duration of maintenance macrolide antibiotic therapy in obstructive airway disease (OAD) remains unclear. This study evaluated the impact of de-escalating maintenance macrolide therapy during the Australian summer on OAD exacerbations. METHODS: This double-blind, placebo-controlled, non-inferiority trial recruited 82 participants (mean age: 67.33±13.13; 55% female) undergoing maintenance macrolide therapy for the management of asthma, chronic obstructive pulmonary disease or bronchiectasis. They were randomised to continue (continuation arm) or de-escalate macrolide therapy (de-escalation arm) at the start of the summer (December-February). Follow-up interviews were conducted at 3, 6 and 9 months. The primary outcome was acute exacerbations during the summer. Secondary outcomes included symptom control scores and time to first exacerbation. The non-inferiority margin was 20%. RESULTS: The acute exacerbation rates were 33.3% (14/42) for the continuation arm and 50% (19/38) for the de-escalation arm during the summer season. The primary analysis did not demonstrate non-inferiority (risk difference 16.2%; 95% CI -4.9% to 37.2%, with the upper bound exceeding the 20% non-inferiority margin). Symptom control was maintained and did not differ between arms. The time to first exacerbation was longer in the continuation arm (median 206 vs 90 days; HR 1.98, 95% CI 1.15 to 3.42; p=0.012). CONCLUSION: Macrolide de-escalation was not found to be non-inferior to continued treatment in individuals with OAD. While some patients may be able to discontinue long-term macrolide therapy during the summer, there remains a risk of exacerbation recurrence. TRIAL REGISTRATION NUMBER: ACTRN12620001263987.

Abstract as published, via PubMed.