Association between incidence of acute exacerbation and medication therapy in patients with COPD

Abstract

Background:

As exacerbations of chronic obstructive pulmonary disease (COPD) significantly worsen patients’ health status and increase disease-related mortality, greater control of exacerbations has important implications for improving patients’ health and survival. The incremental benefits of pharmacologic therapies in preventing COPD exacerbations remain unclear. The objective of this observational study was to examine the risk of COPD-related exacerbations between groups of patients receiving inhaled corticosteroids (ICS), anticholinergics (AC), long-acting β₂-agonists (LABA), or fixed-dose combinations of ICS and LABA.

Methods:

A 12-month retrospective cohort analysis of 2923 patients, who were at least 40 years old with the first time COPD in 12 months (i.e., no COPD for 12 months prior to this time) between 2000 and 2004, was conducted using the MarketScan research databases. Patients with at least two prescriptions for ICS, AC, LABA, or ICS + LABA during the observation period were followed from the index prescription date for the duration of the study. COPD-related exacerbations were defined as clinical events in which a primary diagnosis for a respiratory condition had resulted in hospitalization, an emergency room visit, or an outpatient visit followed by a prescription fill of oral corticosteroids or antibiotics within 14 days of the visit. Exacerbation rates were evaluated using a Cox proportional hazard model with adjustment for age, gender, comorbidities, hospitalizations, emergency room visits, and the number of outpatient visits.

Findings:

Compared with ICS alone, COPD exacerbation rates were 35% (CI:22–42%) lower with ICS + LABA, 32% (CI:13–43%) lower with LABA, and 28% (CI:15–36%) lower with AC. The hazard ratio of the first observed COPD exacerbation was 13–18% lower with the use of bronchodilators, with or without ICS, than with ICS alone. In addition, patients receiving ICS alone experienced more exacerbations during the 12-month period following initiation of therapy than those patients receiving LABA, AC, or ICS + LABA. Generalizability of the results and randomization of treatments were limited due to nature of the administrative claim databases.

Conclusion:

The present study found that use of bronchodilators, with or without ICS, in COPD patients resulted in a lower exacerbation rate when compared with ICS monotherapy. Further research is required to understand the clinical effects of specific pharmacologic therapies on COPD exacerbations, as well as their impact on long-term outcomes and costs.

Key words::

• Anticholinergics
• Bronchodilator
• Chronic obstructive pulmonary disease
• Exacerbations
• Inhaled corticosteroids
• Long-acting β₂-agonists
• Risk assessment

Transparency

Declaration of funding

The study was partially funded by an unrestricted research grant from Novartis Pharmaceuticals Corporation.

Declaration of financial/other relationships

D-C.S. has disclosed that he has received research grants from Novartis. H.L. and G.P.G. have disclosed that they are employees of Novartis.

Some peer reviewers receive honoraria from CMRO for their review work. The peer reviewers of this paper have disclosed that they have no relevant financial relationships.

Acknowledgment

The authors thank C Plauschinat, W Grant and S. Mahajan for their comments on the design of the study, and Sarah Filcek for assistance with manuscript preparation.