1. Long-term macrolide therapy for chronic obstructive pulmonary disease: a population-based time series analysis
- Author
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Gary Garber, Farah E Saxena, Jennie Johnstone, Kevin L Schwartz, Andrew Calzavara, Matthew Kumar, Samantha Lee, Marie Yan, Bradley J Langford, Andrea S. Gershon, Nick Daneman, and Kevin A. Brown
- Subjects
Male ,medicine.medical_specialty ,Respiratory System Agents ,Severity of Illness Index ,Interrupted Time Series Analysis ,Time ,Pulmonary Disease, Chronic Obstructive ,Internal medicine ,Outcome Assessment, Health Care ,Medicine ,Humans ,Adverse effect ,Aged ,Ontario ,COPD ,Duration of Therapy ,business.industry ,Incidence (epidemiology) ,Research ,General Medicine ,Emergency department ,Antibiotic Prophylaxis ,medicine.disease ,Symptom Flare Up ,Confidence interval ,Anti-Bacterial Agents ,Hospitalization ,Cohort ,Adjunctive treatment ,Disease Progression ,Female ,Macrolides ,business - Abstract
Background Macrolides are recommended as an adjunctive treatment for patients with moderate to severe chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations. The objective of this study was to examine temporal trends in the provision of long-term macrolide therapy, specifically before and after publication of the landmark MACRO trial in August 2011 showing efficacy of macrolides for this indication. Methods We performed an interrupted time series analysis using population-level health administrative data. The study cohort consisted of all Ontario residents who had COPD, were using at least 1 long-acting inhaler, and were aged 65 years and older between Apr. 1, 2004, and Mar. 31, 2018. We compared the baseline characteristics of eligible patients before and after publication of the MACRO trial. Our primary outcome was overall prevalence of long-term macrolide therapy; secondary outcomes were incidence of COPD-related hospitalizations, emergency department visits and outpatient exacerbations requiring high-dose steroids in each quarter. We performed an interrupted time series analysis to assess for changes in the incidence of macrolide prophylaxis by quarter-year over the study period. Results The rate of long-term macrolide use increased from 0.8 per 1000 people in 2004 to 13.8 per 1000 people in 2018 (in the severe COPD group, the rate increased from 1.3 to 32.3 per 1000 people). The interrupted time series analysis showed that, before 2011, the prevalence of macrolide prophylaxis increased at a rate of 0.44 (95% confidence interval [CI] 0.39-0.50) per 1000 people per year; after 2011, the rate of increase grew by 1.18 (95% CI 1.07-1.29) per 1000 people to 1.63 (95% CI 1.56-1.69) per 1000 people per year. The seasonal pattern of COPD-related health care visits remained stable over the study period, and there was no detectable reduction in hospitalizations or emergency department visits at the population level. Interpretation In the past decade, there has been a significant rise in the use of long-term macrolide therapy for patients with COPD. As this practice becomes increasingly common, it will be important to monitor its potential benefits on COPD exacerbations but also its potential effects on adverse events and antimicrobial resistance patterns.
- Published
- 2021