A meta-analysis on the prophylactic use of macrolide antibiotics for the prevention of disease exacerbations in patients with Chronic Obstructive Pulmonary Disease

Abstract

Introduction: Macrolides are of unique interest in preventing COPD exacerbations because they possess a variety of antibacterial, antiviral and anti-inflammatory properties. Recent research has generated renewed interest in prophylactic macrolides to reduce the risk of COPD exacerbations. Little is known about how well these recent findings fit within the context of previous research on this subject. The purpose of this article is to evaluate, via exploratory meta-analysis, whether the overall consensus favors prophylactic macrolides for prevention of COPD exacerbations.

Methods: EMBASE, Cochrane and Medline databases were searched for all relevant randomized controlled trials (RCTs). Six RCTs were identified. The primary endpoint was incidence of COPD exacerbations. Secondary endpoints including mortality, hospitalization rates, adverse events and likelihood of having at least one COPD exacerbation were also examined.

Results: There was a 37% relative risk reduction (RR = 0.63, 95% CI: 0.45-0.87, p value = 0.005) in COPD exacerbations among patients taking macrolides compared to placebo. Furthermore, there was a 21% reduced risk of hospitalization (RR = 0.79, 95% CI: 0.69-0.90, p-value = 0.01) and 68% reduced risk of having at least one COPD exacerbation (RR = 0.34, 95% CI 0.21-0.54, p-value = 0.001) among patients taking macrolides versus placebo. There was also a trend toward decreased mortality and increased adverse events among patients taking macrolides but these were not statistically significant.

Conclusions: Prophylactic macrolides are an effective approach for reducing incident COPD exacerbations. There were several limitations to this study including a lack of consistent adverse event reporting and some degree of clinical and statistical heterogeneity between studies.

Keywords: Antibiotic prophylaxis; COPD; COPD exacerbation; Chronic Obstructive Pulmonary Disease; ITT; Intention-to-Treat; Macrolides; Meta-analysis; RCT; randomized controlled trial.