COPD Landmark Trial UPLIFT Proves Tiotropium Sustains Lung Function Improvements Over Four Years and Improves Survival Rate
05/10/2008 14:05
PR Newswire
BERLIN, October 5 /PRNewswire/ --
- Results of 5,993 Patient Study UPLIFT (Understanding Potential
Long-term Impacts on Function with Tiotropium) Presented Today at European
Respiratory Society Annual Congress
- Not for U.S. Media
Results of the UPLIFT trial, presented today at the European
Respiratory Society (ERS) Annual Congress, demonstrated that tiotropium
(SPIRIVA) administered to Chronic Obstructive Pulmonary Disease
(COPD)patients, showed sustained improvements in lung function for up to 4
years (pfunction. The landmark study also reaffirmed the favourable safety profile of
tiotropium.(1)
To view the Multimedia News Release, please click:
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UPLIFT also demonstrated that tiotropium produced a significant delay
in time to first exacerbation by a median of 4.1 months (psignificant reduction in the number of exacerbations per patient year (14%;
pleading to hospitalisations (Hazard Ratio 0.86; pgroup. Exacerbations can worsen the clinical course of the disease, so a
treatment that significantly reduces exacerbations can positively impact the
clinical course of COPD.(2)
UPLIFT, one of the largest COPD trials ever undertaken,involved 5,993
COPD patients from 37 countries around the globe. UPLIFT is a landmark COPD
trial comparing tiotropium 18 microg once daily with placebo, and allowed all
patients to continue with their normally prescribed respiratory medications,
including dose adjustments throughout the trial, except inhaled
anticholinergics.
Tiotropium also provided statistically significant improvements in
health-related quality of life, as measured by the St.George's Respiratory
Questionnaire (SGRQ, p
Throughout the four-year trial period, patients in the
tiotropium group consistently reported a better quality of life than at study
initiation.
Further, a statistically significant 16% decrease in the risk of death
(p=0.016) was observed in the tiotropium group, while patients received
treatment. Within the four year treatment period of the trial, the effect on
survival was sustained, even when deaths occurring after early
discontinuation of study medication were included in the analysis (p=0.034).
Risk of mortality was assessed for the 30 days following the conclusion of
the treatment period, and the study revealed an 11% reduced risk of death,
although it did not meet statistical significance (p=0.086).
Importantly, tiotropium reduced respiratory (pmorbidity (ptiotropium. As in previous studies the most commonly observed side effect was
dry mouth.
Professor Marc Decramer, lead investigator and Professor of Medicine at
the Catholic University Hospital in Leuven, Belgium said: "UPLIFT faced a
considerable challenge to demonstrate treatment benefits - unlike most other
respiratory trials; it allowed all patients to be treated with all other
concomitant respiratory medications, except for inhaled anticholinergics. In
UPLIFT, tiotropium performed very well over the long term by improving
survival rates, lung function, exacerbation rates, and patients' quality of
life, while also confirming its favourable safety profile. The UPLIFT data
adds to the growing knowledge of how treatment can impact the clinical course
of COPD. This will allow physicians to prescribe a long-term maintenance
treatment early on with confidence."
The data also demonstrate that tiotropium provides important benefits in
moderate disease severity patients (GOLD-Global Initiative for Chronic
Obstructive Lung Disease- Stage II). Forty-six percent of the patients in the
UPLIFT trial were GOLD Stage II. This is one of the largest COPD Stage II
patient populations ever studied over four years. The results obtained for
this patient group are especially relevant as this is the stage when patients
normally first seek treatment for COPD symptoms.
"The results from UPLIFT are good news, especially for primary care
physicians who are usually the first medical contact a patient has once they
decide to seek treatment. UPLIFT provides the confidence that treatment
benefits of tiotropium are sustained long-term, and COPD patients can lead
more active lives for longer," said Dr. Anders 0strem, MD, Specialist in
Family Medicine, Oslo, Norway and past President of International Primary
Care Respiratory Group.
UPLIFT proves tiotropium sustains positive effects for patients with
COPD. "Patients report feeling better and the benefit seen in survival rates
offers more hope to patients, their families, and their physicians,"
commented Dr Andreas Barner, Vice Chairman of the Board of Managing Directors
at Boehringer Ingelheim, responsible for Research, Development and Medicine.
"Most importantly, the four-year study highlights the favourable safety
profile of tiotropium. Almost 6,000 patients were followed for up to four
years, adding to the more than 10 million patient years of market experience
for Spiriva."
Notes to Editors
About COPD
COPD is a progressive yet treatable disease that restricts patients'
lives over time and is a major cause of death and disability throughout the
world. Symptoms include cough, sputum (mucus or phlegm) production, and
breathlessness on exertion. Worsening of these symptoms often occurs and can
restrict a patient's ability to perform normal daily activities. (2) The
latest World Health Organization (WHO) figures estimate that 210 million
people are currently living with COPD and more than 3 million people died
from the disease in 2005(3) - more than breast cancer and diabetes
combined.(4) Dyspnoea (breathlessness), the main symptom of COPD, is
characteristically persistent and progressive and has a serious impact on
patients' quality of life.(2) At its most severe, it even limits a patient
from simple tasks such as washing and dressing.
UPLIFT Study Design
The four-year study was a multicentre (470 sites), multinational (37
countries), randomised, double-blind, placebo-controlled, parallel-group
trial which commenced in December 2002. The study included 5993 male and
female COPD patients. Patients were randomised 1:1 to receive either 18
microg tiotropium or placebo once daily. In both arms, patients were allowed
to take all other respiratory medications usually prescribed for the
treatment of COPD, except for inhaled anticholinergics.
About tiotropium (SPIRIVA)
Tiotropium, a long-acting inhaled anticholinergic medication, is the
first inhaled treatment to provide significant and sustained improvements in
lung function with once-daily dosing. Tiotropium positively impacts the
clinical course of COPD, helping to change the way patients live with their
disease.(5),(6) It is the most prescribed medication for the treatment of
COPD in the world.
Tiotropium works through targeting of a dominant reversible mechanism of
COPD - cholinergic bronchoconstriction. Tiotropium helps COPD patients
breathe easier by opening narrowed airways and helping to keep them open for
24 hours.
Tiotropium has demonstrated significant and sustained bronchodilation
(opening of the airways)(7) and reduction in hyperinflation (air
trapping).(8, 9) Tiotropium also demonstrated superior and sustained
improvements in lung function (FEV1) over ipratropium bromide (ATROVENT)
Inhalation Aerosol, a current first-line therapy for COPD, which were
maintained over one year (6) and has also demonstrated superior improvement
in key lung function parameters over salmeterol.(10) In addition, in placebo
controlled studies, patients treated with tiotropium had less activity
induced breathlessness and improved exercise endurance. They required fewer
doses of rescue medications, had fewer exacerbations and COPD-related
hospitalizations. (7) In clinical trials, the most common adverse reaction
reported with tiotropium was dry mouth, which was usually mild and often
resolved spontaneously during treatment. (7) Long-acting bronchodilators,
including tiotropium, are a preferred maintenance therapy for COPD from stage
II onwards according to the Global Initiative for Chronic Obstructive Lung
Disease (GOLD) treatment guidelines. (2)
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 135 affiliates in 47 countries and 39,800 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 2007, Boehringer Ingelheim posted net sales of 10.9 billion Euro while
spending one fifth of net sales in its largest business segment Prescription
Medicines on research and development.
For more information please visit http://www.boehringer-ingelheim.com
About Pfizer Inc
Founded in 1849, Pfizer is the world's largest research-based
pharmaceutical company taking new approaches to better health. We discover,
develop, manufacture and deliver quality, safe and effective prescription
medicines to treat and help prevent disease for both people and animals. We
also partner with healthcare providers, governments and local communities
around the world to expand access to our medicines and to provide better
quality health care and health system support. At Pfizer, more than 80,000
colleagues in more than 90 countries work every day to help people stay
happier and healthier longer and to reduce the human and economic burden of
disease worldwide.
Webcast and additional media materials
To view the UPLIFT Breaking News press briefing at the European
Respiratory Society's annual congress in Berlin, Germany, please visit
http://www.livecoder.com/clients/bi/20081005_berlin/rmf_dsl_eng.html
The briefing will be available for live viewing on Sunday, 5 October
16:00-16:45 (CET) and available on demand from Sunday, 5 October 18:00 (CET).
Journalists may want to download additional information here:
http://www.boehringer-ingelheim.com/corporate/news/presspack/uplift_2008/inde
x.asp
References
---------------------------------
(*) Health-related quality of life was evaluated using the Saint George's
Respiratory Questionnaire (SGRQ), where a four-point decrease in SGRQ score
is considered to be a clinically meaningful improvement in a patient's
health-related quality of life.
---------------------------------
(1) Tashkin DP, Celli B, Senn S, et al. A 4-year trial of tiotropium in
chronic obstructive pulmonary disease. N Engl J Med 2008; 359: 1543-54.
(2) Global Initiative for Chronic Obstructive Lung Disease. Global
Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive
Pulmonary Disease:
http://www.goldcopd.com/Guidelineitem.asp?l1=2?2=1?=989 Updated: 2007
(3) Source: World Health Report. World Health Organization. Available
from URL: http://www.who.int/respiratory/copd/en/
(4) World Health Organization. World Health Report 2004. Statistical
Annex. Annex table 2 and 3: 120-131.
(5) Casaburi R, Kukafka D, Cooper CB, et al. Improvement in exercise
tolerance with the combination of tiotropium and pulmonary rehabilitation in
patients with COPD. Chest 2005; 127:809-817.
(6) Vincken W, van Noord JA, Greefhorst APM, et al. Improved health
outcomes in patients with COPD during 1 year's treatment with tiotropium. Eur
Respir J 2002; 19:209-216.
(7) Casaburi R, Mahler DA, Jones PW, et al. A long-term evaluation of
once-daily inhaled tiotropium in chronic obstructive pulmonary disease. Eur
Respir J. 2002; 1:217-224.
(8) Celli B, ZuWallack 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.
(9) 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
(10) 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.
Contact:
Boehringer Ingelheim GmbH
External Communications
Ute E Schmidt
Binger Strasse 173
55216 Ingelheim am Rhein
Germany
Tel.: +49-6132-779-7296
Head External Communications
Judith von Gordon
Binger Strasse 173
55216 Ingelheim am Rhein
Germany
Tel.: +49-6132-773-582
E: press@boehringer-ingelheim.com
Pfizer Inc.
Director European Communications
Oliver Stohlmann
Tel: +43-152-115-337
E: oliver.stohlmann@pfizer.com
Investor Relations
Jennifer Davis
Tel: +1-212-733-0717
E: jennifer.m.davis@pfizer.com
Contact: Boehringer Ingelheim GmbH, External Communications, Ute E Schmidt, Binger Strasse 173, 55216 Ingelheim am Rhein, Germany, Tel.: +49-6132-779-7296; Head External Communications, Judith von Gordon, Binger Strasse 173, 55216 Ingelheim am Rhein, Germany, Tel.: +49-6132-773-582, E: press@boehringer-ingelheim.com; Pfizer Inc., Director European Communications, Oliver Stohlmann, Tel: +43-152-115-337, E: oliver.stohlmann@pfizer.com; Investor Relations, Jennifer Davis, Tel: +1-212-733-0717, E: jennifer.m.davis@pfizer.com
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