Long-term macrolide treatment for the prevention of acute exacerbations in COPD: a systematic review and meta-analysis

Abstract

Background

Acute exacerbation of COPD (AECOPD) is associated with an increased hospitalization and mortality. Azithromycin and erythromycin are the recommended drugs to reduce the risk of exacerbations. However, the most suitable duration of therapy and drug-related adverse events are still a matter of debate. The aim of this meta-analysis was to assess the current evidence regarding the efficacy and safety of long-term macrolide treatment for COPD.

Materials and methods

We comprehensively searched PubMed, Embase, the Cochrane Library, and the Web of Science and performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) and retrospective studies.

Results

Eleven RCTs and one retrospective study including a total of 2,151 cases were carried out. Long-term macrolide treatment significantly reduced the total number of cases with one or more exacerbations (OR=0.40; 95% CI=0.24–0.65; P<0.01) and the rate of exacerbations per patient per year (risk ratio [RR]=0.60; 95% CI=0.45–0.78; P<0.01). Subgroup analyses showed that the minimum duration for drug efficacy for both azithromycin and erythromycin therapy was 6 months. In addition, macrolide therapy could improve the St George Respiratory Questionnaire (SGRQ) total score (P<0.01) but did not achieve the level of clinical significance. The frequency of hospitalizations was not significantly different between the treatment and control groups (P=0.50). Moreover, chronic azithromycin treatment was more likely to increase adverse events (P<0.01).

Conclusion

Prophylactic azithromycin or erythromycin treatment has a significant effect in reducing the frequency of AECOPD in a time-dependent manner. However, long-term macrolide treatment could increase the occurrence of adverse events and macrolide resistance. Future large-scale, well-designed RCTs with extensive follow-up are required to identify patients in whom the benefits outweigh risks.

Keywords:

• AECOPD
• macrolide
• azithromycin
• adverse events

Supplementary materials

Figure S1 Sensitivity analyses of the total number of patients with one or more exacerbations treated with macrolides compared with the control.

Abbreviation: M–H, Mantel–Haenszel method.

Figure S2 Sensitivity analyses of risk ratios for exacerbations per patient per year treated with macrolides compared with the control.

Figure S3 Sensitivity analyses of the total number of patients requiring hospitalization treated with macrolides compared with the control.

Abbreviation: M–H, Mantel–Haenszel method.

Figure S4 Sensitivity analyses of the mean differences with respect to change in total SGRQ score among patients treated with macrolides compared with the control.

Abbreviation: SGRQ, St George Respiratory Questionnaire.

Figure S5 Sensitivity analyses of the total number of patients who experienced adverse events during follow-up after treatment with macrolides compared with the control.

Abbreviation: M–H, Mantel–Haenszel method.

Table S1 Sensitivity analyses of subgroup based on the number of patients with exacerbations and adverse effects

Acknowledgments

This study was supported by the National Science Foundation of China (No 81400032, No 81600031, and No 81873410) and the National Key Clinical Specialty Construction Projects of China.

Author contributions

Yanan Cui, Yan Chen, and Ping Chen conceived and designed the experiments. Yanan Cui, Lijuan Luo, and Chenbei Li were responsible for acquisition of data. Yanan Cui analyzed the data and wrote the paper. All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.