Three-year results from ECLIPSE study indicate that COPD patients may require prevention strategies to manage exacerbations, regardless of disease severity

Today the New England Journal of Medicine published results from ECLIPSE (Evaluation of COPD* Longitudinally to Identify Predictive Surrogate End-points), an extensive research programme sponsored by GlaxoSmithKline (GSK) designed to advance understanding of the underlying mechanisms of Chronic Obstructive Pulmonary Disease (COPD), a disease which accounts for 2.75 million deaths worldwide each year¹, as well as define markers of disease progression.²

In this three-year observational study, COPD exacerbations were found to become more frequent and more severe as a patient’s disease worsened. However, the single strongest predictor of exacerbations was found to be a prior history of exacerbation, which was observed across all patients, regardless of their disease severity. This suggests that the ‘frequent exacerbator’ is a distinct sub-group (or phenotype) of patients who could be identified and targeted with specific exacerbation prevention strategies. COPD severity was measured using the standard GOLD stage classification which is currently defined by the degree of airflow obstruction as GOLD Stage II-IV (impaired airflow from the lungs on exhalation.** This finding may lead to improved future treatment strategies by encouraging COPD patients to have plans for the prevention and management of exacerbations, regardless of disease severity.

Commenting on the results, Professor Jørgen Vestbo, ECLIPSE Steering Committee Co-chair said, “Exacerbations have a huge impact on the patient and on healthcare systems as well as accelerating a patient’s decline in lung function. These results have shown us that exacerbations are of concern across the spectrum of COPD disease severity. Previously, exacerbations have been associated with more severe disease but our observations in ECLIPSE suggest that patients with less severe disease may require prevention strategies to reduce subsequent exacerbations.”

Frequency and effect of exacerbations was analysed in 2,138 ECLIPSE patients over three years, with exacerbations defined as events requiring patients to be treated with prescription antibiotics or corticosteroid therapy (moderate exacerbation), or to be hospitalised (severe exacerbation).¹ The authors found exacerbation rates in GOLD stage II, III and IV to be 0.85, 1.34 and 2 exacerbations per year, with 22, 33 and 47% respectively of GOLD stage II, III and IV patients being classified as ‘frequent exacerbators’.¹ In addition to disease severity and prior history of exacerbations, exacerbation frequency was independently associated with a history of heartburn, poorer quality of life and elevated level of leukocytes (white blood cells that respond to infections) in the blood.¹

Darrell Baker, SVP GSK Respiratory and Immuno-Inflammation Medicines Development Centre commented, “We are very proud of this collaborative project between GSK and external experts. ECLIPSE is unprecedented, and has inspired several new collaborations within the global research community in COPD that will continue to provide valuable insights in the coming years

COPD is the fourth leading cause of death worldwide and is associated with substantial morbidity.³ COPD is a multicomponent disease, which despite increasing in prevalence, remains poorly understood due to its complex effects on both the lungs and other organs.⁴

Additional information and updates about the ECLIPSE study are available from the ECLIPSE website www.eclipse-copd.com.

Notes to Editors

About ECLIPSE

The ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points) study is a non-interventional, observational, multicentre, three-year study in subjects with Chronic Obstructive Pulmonary Disease (COPD) as well as in smoking and non-smoking control subjects.

The ECLIPSE study is led by a Steering Committee and a Scientific Committee of international COPD experts and GSK staff. Full details of committee members can be found at www.eclipse-copd.com.

ECLIPSE has four specific aims: definition of clinically relevant COPD subtypes; identification of parameters that predict disease progression in these subtypes; examination of biomarkers that correlate with COPD subtypes and may predict disease progression and identification of novel genetic factors and/or biomarkers that both correlate with clinically relevant COPD subtypes and predict disease progression.²

ECLIPSE included 2,180 COPD subjects in Global Initiative for Chronic Obstructive Lung Disease (GOLD) categories II–IV, plus 343 smoking and 223 non-smoking control subjects.² Assessments in the ECLIPSE study included pulmonary function measurements (spirometry, impulse oscillometry and plethysmography), chest computed tomography, biomarker measurement (in blood, sputum, urine and exhaled breath condensate), health outcomes, body impedance, resting oxygen saturation and 6-min walking distance.² Study assessments were performed at baseline, 3 months, 6 months and every 6 months thereafter for the three year duration of the study.²

Current diagnosis and staging of COPD is made using forced expiratory volume in one second (FEV₁), but it is widely accepted that this has limitations as it only measures one aspect of the disease and is less predictive of disease progression, especially in early disease.^5-7 The components of COPD can be of either a structural (including airway remodelling, emphysema, skeletal muscle wasting) or functional nature (inflammation, apoptosis, senescence).⁴ Studies such as ECLIPSE that help to characterise the multicomponent nature of COPD are needed to improve understanding, diagnosis and treatment of the condition.

*Chronic Obstructive Pulmonary Disease

**Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage classification is a standard measure of COPD disease severity.

GlaxoSmithKline – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit www.gsk.com