Landmark study shows important benefits of Seretide treatment for patients with fatal lung disease, COPD
New England Journal of Medicine today publishes results of largest ever study completed investigating the effect of treatment on mortality and morbidity in patients with chronic obstructive pulmonary disease (COPD) 1
Issued: Wednesday 21 February 2007, London, UK
Results of the TOwards a Revolution in COPD Health (TORCH)study, the largest of its kind, have been published today in the New England Journal of Medicine 1 and represent a landmark in COPD, a disease which kills more people each year than breast cancer and lung cancer combined.2,3 The results show important benefits of Seretide in the treatment of patients with COPD. The three year study was designed to investigate reductions in death from any cause as the primary endpoint and also measured improvements in exacerbations (or worsening of symptoms) and quality of life as key secondary findings. The results from TORCH have been submitted to the regulatory authorities for consideration for inclusion into Seretide prescribing information.
In this study Seretide Diskus (50/500µg) treatment was associated with a 17.5% reduction in the risk of dying from any cause over three years (p=0.052) compared to placebo. This did not meet the predetermined level of statistical significance ofp=0.050. Seretide, when compared with placebo, also showed a 25% (p<0.001) reduction in the rate of exacerbations, which are a worsening of the patient’s condition often causing increased difficulty in breathing. Exacerbations are a major cause of hospitalisation and have significant physical and psychological effects on patients, many of whom never fully recover from the impact. 4
Those treated with Seretide also showed an improvement in health related quality of life and FEV1, an established measure of lung function in patients with COPD, vs placebo over the three years of the study (p<0.001). While typically the health status of patients with COPD declines over time, patients receiving Seretide showed an improvement and their health status at the end of the three years remained above the baseline that they started from at the beginning of the study. For patients with COPD quality of life is severely affected, patients frequently
experience anxiety, hopelessness and depression5,6. In addition fatigue, commonly aggravated by sleep disturbances, and breathlessness, can not only severely limit physical activity, but in turn can also impact on a patient’s economic and social roles.7 Up to 75% of patients with COPD report difficulty in the simplest of everyday activities, such as being out of breath after walking upstairs.8
Commenting on the results, lead investigator Professor Peter Calverley said: “We are very proud of undertaking such an ambitious study. This is the first time a study has been carried out to investigate whether a medicine can have an impact on both survival and improvements in quality of life in patients with COPD. The steering committee for TORCH believes that these results are clinically important and have progressed our understanding of this disabling and potentially fatal disease, so that we can make informed choices in the treatment and management of our patients.”
There was an increased risk of pneumonia seen as adverse events or serious adverse events in the inhaled corticosteroid containing arms of the TORCH study. The number of deaths while on treatment which were attributable to pneumonias, as adjudicated by the Clinical Endpoints Committee, was 7 in the placebo group, 9 in the salmeterol group, 13 in the fluticasone propionate group, and 8 in the Seretide group. Treatment with Seretide did not appear to be associated with an increased risk of COPD patients dying from pneumonia. There were no increases in bone or eye disorders in patients treated with Seretide compared with placebo.1
Current guidelines state that in addition to relieving symptoms, preventing exacerbations and improving health-related quality of life, reducing mortality is a goal of COPD treatment.9 TORCH is the first study to investigate whether medication can affect survival in patients with COPD; to date smoking cessation, home oxygen treatment and lung volume reduction surgery are the only therapies shown to improve survival in patients with COPD.1
Darrell Baker, head of the Respiratory Medicines Development Centre for GSK, said: “We are delighted with the results of this landmark study. The results have been submitted to regulatory authorities world-wide for consideration for inclusion into Seretide prescribing information.”
The TORCH study was sponsored by GlaxoSmithKline.
About GSK
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 company information visit www.gsk.com.
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Notes to editors
About COPD
Chronic Obstructive Pulmonary Disease (COPD) is a debilitating and potentially fatal disease, but it can be both prevented and treated. The disease has a number of different components causing limitations to airflow in the lungs and breathing difficulties. These include increased inflammation in the airways, direct damage and structural changes to the lungs and reduced body mass, weakness and wasting, which affect the health status of the person and ultimately their survival. Improving survival remains a major unmet need for patients with COPD1.
By 2020 COPD is projected to be the third leading cause of death and fifth leading cause of disability worldwide following only ischaemic heart disease, depression, traffic accidents and cerebrovascular disease10. COPD is estimated to kill more than 250 people per hour worldwide11
About TORCH
TORCH (TOwards a Revolution in COPD Health) is the first and largest study to prospectively investigate the potential for Seretide (salmeterol/fluticasone propionate, SFC) 50/500 µg to impact survival in patients with Chronic Obstructive Pulmonary Disease (COPD). TORCH is a three year, multicentre, randomised, double-blind, parallel group placebo controlled study. Approximately 6,100 patients meeting the European Respiratory Society definitions for COPD were randomised from 439 sites in 42 countries to one of the following 4 treatment groups:1
- Placebo
- Salmeterol (50 µg)
- Fluticasone propionate (500 µg)
- Seretide (SFC, 50/500 µg), all inhaled twice daily via the Diskus
In all treatment arms patients were allowed to take other medications to treat COPD symptoms including anticholinergics, theophylline and salbutamol (similar usage was seen across treatment arms). Patients were instructed not to take inhaled corticosteroids, long-term oral corticosteroids or long-acting bronchodilators while enrolled in the study.
The primary end point of TORCH was the reduction in all-cause mortality, comparing SFC with placebo. Secondary endpoints include:1
- COPD morbidity (as measured by the rate of exacerbations [moderate requiring systemic corticosteroids and/or antibiotics or severe requiring hospitalisation])
- Quality of life (as measured by St George’s Respiratory Questionnaire (SGRQ))
In the TORCH trial, the reduction in all-cause mortality between SFC and placebo groups did not meet the pre-specified significance level. In the NEJM paper, the authors suggest that the lower than anticipated number of deaths and the high withdrawal rate in patients receiving placebo, who were free to receive active therapy subsequently, including Seretide, may have contributed to the final results not reaching statistical significance.1
About Seretide / Advair
The brand name for fluticasone propionate / salmeterol in the European Union (excluding Germany) is Seretide. The brand name of fluticasone propionate / salmeterol in Germany is Viani™. The brand name for fluticasone propionate / salmeterol in the US is Advair.
Seretide is a combined treatment of fluticasone propionate, an inhaled corticosteroid and salmeterol, a long acting bronchodilator. Each component targets different aspects of the pathophysiology of COPD a multi-component disease with inflammation at the core.
The inflammation seen in patients with COPD is present even in the early stages of the disease and is associated with disease progression.12 Seretide has been shown to have a broad range of anti-inflammatory effects in COPD which are greater than those seen with inhaled corticosteroids (ICS) in single treatment.13,14
Seretide / Viani 50/500 is licensed in the European Union for the symptomatic treatment of patients with severe COPD (forced expiratory volume in one second FEV1 < 50% predicted normal) and a history of repeated exacerbations, who have significant symptoms despite regular bronchodilator therapy.
Advair 50/250 is licensed in the US for twice-daily maintenance treatment of airflow obstruction in patients with COPD associated with bronchitis. Advair Diskus 50/500 is not approved for treatment of COPD in the US.
Seretide/Advair 50/250 and 50/500 is approved for the treatment of COPD in over 40 additional countries including Australia, Canada, Mexico and Turkey.
References
1. Peter M.A. Calverley M.D. et al on behalf of the TORCH investigators. Salmeterol and fluticasone propionate and survival in Chronic Obstructive Pulmonary Disease. NEJM 2007; 356: 775-789
2. WHO. The World Health Report 2002. Reducing risks, promoting healthy life
3. Ferlay J, et al., GLOBOCAN 2002. Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase No.5, Version 2.0. IARCPress, Lyon, 2004. 2004
4. Seemungal TAR, Donaldson GC, Bhowmik A, Jeffries DJ, Wedzicha JA. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 161: 1608-1613
5. Thompson WL. Pulmonary Disease. In: Stoudemire A, Fogel BS, Greeberg DB, eds. Psychiatric care of the medical patient. 2nd ed. New York, NY: OxfordUniversityPress; 2000:757-774.
6. Kunik ME, Roundy K, Veazey C, Souchek J, Richardson P, Wray NP, StanleyMA. Surprisingly High Prevalence of Anxiety and Depression in Chronic Breathing Disorders. Chest 2005; 127;1205-1211
7. European Federation of Allergy and Airway Diseases Patients Association. European COPD Patient Manifesto. www.efanet.org. (Last accessed 17 January 2007).
8. Vermeire P. The burden of chronic obstructive pulmonary disease. Respir Med 2002: 96(Suppl C): S3-S10.
9. Global Initiative for Chronic Obstructive Lung Disease 2006. Global strategy for the diagnosis, management, and prevention of COPD. Available from www.goldcopd.org (last accessed 12th January 2007)
10. European Respiratory Society, European Lung Federation, European Lung White Book, 2003.
11. WHO. The World Health Report 2002. Reducing risks, promoting healthy life. MDI.WHR.202.A. Geneva, The World Health Organization; 2002
12. Hogg JC, ChuF. The Nature of Small-Airway Obstruction in Chronic Obstructive Pulmonary Disease. NEMJ 2004; 350;26
13. Yamauchi Y, Christodoulopoulos P, Olivenstein R, Maltais F, Bourbeau J, Hamid Q. The Effect of Salmeterol/Fluticasone Combination on Airway Inflammation in COPD Compared to Fluticasone. PATS 2006; 3(abstracts issue): A113
14. Barnes N, Qiu Y, Pavord I et al. Antiinflammatory Effects of Salmeterol/Fluticasone Proprionate in Chronic Obstructive Lung Disease. Am J Respir Crit Care Med 2006; 173: 736-743
