Applied Evidence

When guideline treatment of asthma fails, consider a macrolide antibiotic

J Fam Pract. 2019 December;68(10):536-540,542-545

References

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No differences between the randomized groups were observed in clinical adverse effects.

Comment: The brief course of azithromycin provided to patients in this trial did not have a significant impact on time to next episode of troublesome lung symptoms in individual children. Previous clinical observations have suggested that a longer duration of treatment (3-6 months) might be required to achieve lasting improvement or remission in selected patients with asthma (see CASE 2).^10,11The short-term benefit of azithromycin for acute wheezing is limited to children: Two comparable acute dosing trials in adults have shown little¹² or no¹³ short-term benefit; however, these negative findings have been hypothesized to be the result of selection bias.¹⁴

Other evidence is worth examining

Other studies not included in the meta-analyses of randomized controlled trials provide additional evidence to support a recommendation of a trial of azithromycin in patients with severe, refractory, or new-onset asthma.

Nonrandomized controlled evidence. AZMATICS (AZithroMycin/Asthma Trial In Community Settings)¹⁵ is the sole randomized, double-blind, placebo-controlled trial of long-term azithromycin that included a 9-month posttreatment observation period. Seventy-five participants were randomized to receive a loading dose of 600 mg of azithromycin or placebo once daily for 3 days in Week 1. They then received either azithromycin 600 mg or placebo once weekly for 11 weeks. Posttreatment observation was performed until 48 weeks after randomization.

However, many eligible subjects, whom the principal investigator believed were ideal candidates for randomization, declined randomization because they did not want to risk receiving placebo. To accommodate those patients, the protocol was amended to include an open-label (OL) azithromycin arm, in which each participant’s personal physician prescribed azithromycin 750 mg for 11 weeks after a loading dose¹⁶ (OL cohort only, Level 2 study: controlled, nonrandomized, nonblinded). The OL group had (1) a higher baseline prevalence of severe, persistent asthma (32%) than the randomized group (8%) (P = .012); and (2) worse asthma quality of life than the randomized patients (P = .023). The OL group represented selection bias attributable to patient preference.

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