Spiriva may slow decline in FEV, a measure of lung function in patients with COPD

Main Category: COPD
Article Date: 07 Apr 2005 - 9:00 PDT

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In a retrospective analysis patients with Chronic Obstructive Pulmonary Disease (COPD) treated with the inhaled, anticholinergic medication Spiriva� (tiotropium) appeared to have a significantly slower decline in FEV1, a measure of lung function, compared to patients receiving placebo, according to a retrospective analysis of two, one year studies published in this month`s edition of Pulmonary Pharmacology and Therapeutics.1 Spiriva� is used as a first-line maintenance therapy for COPD.2

FEV1 is defined as the volume of air that can be forcefully exhaled in one second (FEV1 = Forced expiratory volume in one second). The rate of FEV1 decline is considered the gold standard parameter of disease progression, and has been used in a number of landmark studies to assess the long-term impact of airway medications. To date, no inhaled treatment has been shown to reduce the loss of lung function in patients with COPD.

"These are interesting findings that support further investigation into the potential long-term benefits of Spiriva�," said Professor Antonio Anzueto, primary author, Department of Pulmonary/Critical Care, University of Texas Health Science Centre. "The observations are particularly encouraging in advance of the four-year UPLIFT� trial, currently in progress to prospectively evaluate Spiriva`s� ability to reduce lung function decline and disease progression in patients with COPD."

The now published results are based on a retrospective analysis of two, one-year, randomised, placebo-controlled studies of inhaled tiotropium 18�g once daily in patients with COPD. Participants had a mean age of 65 years, a smoking history of 60-pack-years, and clinically stable airflow limitation (mean FEV1 1.02L).

This retrospective analysis suggests that:

-- Spiriva� may slow pre-dose FEV1 decline vs. placebo: 1
Mean rate of decline in pre-dose FEV1 calculated between days 8 and 344 was 12 ml/year for Spiriva� vs. 58 ml/year for placebo respectively (p=0.005). For post-dose FEV1, there was a trend towards a slower rate of decline with Spiriva� (42ml/yr vs. 50 ml/yr, p≥0.05).

-- Spiriva� significantly improved pre-dose FEV1 vs. placebo: 1
Generally, Spiriva� was superior to placebo by 120-150 ml (p<0.01) in terms of pre-dose FEV1 response throughout the one year observation period. Post-dose FEV1 responses were also favourable for Spiriva� (150-320 ml; p<0.01).

-- Spiriva� effective independent of smoking status: 1
In both ex-smokers and smokers, the rate of decline in pre-dose FEV1 was lower with Spiriva� than placebo.

COPD is a progressive respiratory disease that causes significant deterioration of lung function and chronic breathlessness, which can lead to severe disability.3 Chronic airflow limitation associated with COPD leads to excess air being trapped in the lungs after a person has fully exhaled. This process, known as "air trapping", is a primary cause of breathlessness, which often restricts a patient`s ability to perform daily activities, such as walking up stairs or taking a shower.4,5 Currently, COPD is the fourth leading cause of death worldwide, claiming 2.75 million lives annually.6

Studies are ongoing to confirm these observations. UPLIFT� (Understanding Potential Long-term Impacts on Function with Tiotropium), is a landmark, four-year, randomised, double-blind, placebo-controlled study involving approximately 6,000 patients with COPD in 37 countries. The primary objective of UPLIFT is to determine whether tiotropium reduces the rate of decline in lung function (as measured by FEV1) over time in COPD patients. Other important outcome measures - including health-related quality of life, exacerbations of COPD and mortality - are also being assessed. Results of the clinical trial are expected in 2008.

About Spiriva� (tiotropium)

Spiriva�, a novel inhaled anticholinergic medication, is the first inhaled treatment to provide significant and sustained improvements in lung function with once-daily dosing. Spiriva� works through targeting of a dominant reversible mechanism of COPD - cholinergic constriction. Spiriva� helps COPD patients breathe easier by opening narrowed airways and helping to keep them open for 24 hours.

The Spiriva� clinical trials programme has recruited over 25,000 patients.7 Spiriva� has demonstrated significant and sustained bronchodilation (expansion of the lungs airways)8,9 and reduction in markers of hyperinflation (air trapping).3,10 Spiriva� also demonstrated superior and sustained improvements in lung function (FEV1) over ATROVENT� (ipratropium bromide) Inhalation Aerosol, a current first-line therapy for COPD, which were maintained over one year8 and has also demonstrated superior improvement in key lung function parameters over salmeterol.11 In addition, in placebo-controlled studies, patients treated with Spiriva� required fewer doses of rescue medications.9 In clinical trials, the most common adverse reaction reported with Spiriva� was dry mouth, which was usually mild and often resolved during treatment.8,9

According to treatment guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD), long-acting bronchodilators, including tiotropium, are a preferred treatment option for COPD maintenance therapy.

About Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world`s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 152 affiliates in 45 countries and more than 34,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine. In 2003, Boehringer Ingelheim posted net sales of 7.4 billion euro while spending more than one fifth of net sales in its largest business segment Prescription Medicines on research and development.

Graphics, photos and data for feature articles are available on request.

Contact:

Boehringer Ingelheim GmbH
Judith von Gordon
55216 Ingelheim am Rhein
GERMANY
Phone: +49/6132/77 35 82
Fax: +49/6132/77 66 01
webmaster@ing.boehringer-ingelheim.com

References:

1 Anzueto A, Tashkin D, Menjoge S, Kesten S. One-Year Analysis of Longitudinal Changes in Spirometry in Patients with COPD Receiving Tiotropium. Pulmonary Pharmacology and Therapeutics 2005;18:75-81.

2 Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease. NHLBI/WHO workshop report. Bethesda, National Heart, Lung and Blood Institute, April 2001; Update of the Management Sections, GOLD website (http://www.goldcopd.com). Date updated: July 2003.

3 Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease: NHLBI/WHO Workshop Report. National Institute of Health; (2001). NIH Publication No. 2701 Available at http://www.goldcopd.com.

4 Celli B, Zu, Wallack R, Wang S, et al. Improvement in resting inspiratory capacity and hyperinflation with tiotropium in COPD patients with increased static lung volumes. Chest 2003;124:1743-1748.

5 Mahler DA. How should health related quality of life be assessed in patients with COPD? Chest 2000;117:54S-57S.

6 World Health Organization. World Health Report 2003. Statistical Annex. Annex table 2: 154-159.

7 Boehringer Ingelheim. Data on file.

8 Vincken W, van Noord JA, Greefhorst APM, et al. Improved health outcomes in patients with COPD during 1 year`s treatment with tiotropium. European Respiratory Journal 2002;19:209-216.

9 Casaburi R, Mahler DA, Jones PW, et al. A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease. European Respiratory Journal 2002; 1:217-224.

10 O`Donnell DE, Fluge T, Gerken F, et al. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur Respir J 2004 23(6):832-48

11 Brusasco V, Hodder R, Miravitlles M, et al. Health outcomes following treatment for six months with once daily tiotropium compared with twice daily salmeterol in patients with COPD. Thorax 2003;58:399-404.

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