Landmark UPLIFT Study Shows That Spiriva Improves Lung Function And Reduces Exacerbations And Mortality In COPD

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Main Category: Respiratory / Asthma
Article Date: 06 Oct 2008 - 4:00 PDT

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Treatment with the inhaled anticholinergic tiotropium (Spiriva; Boehringer Ingelheim) significantly improves lung function and quality of life and reduces exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD), according to results from the landmark UPLIFT study reported at the European Respiratory Society annual congress ( 4-8 October 2008; Berlin, Germany). Further results showed no increase in cardiovascular events, confirming the drug's safety.

The study randomised 5993 patients with COPD and reduced lung function (mean FEV₁ of 48% of predicted value) to tiotropium (18mcg once daily) or placebo, in addition to other therapies, including long acting bronchodilators and inhaled corticosteroids (but not anticholinergics) at the discretion of the treating physician.

Results showed that patients treated with tiotropium had significantly greater FEV1 than control patients throughout the four years of the trial (87-103ml before bronchodilation; p<0.001), although both groups showed a similar rate of FEV₁ decline, which was the primary endpoint of the study.

The researchers suggested the low rate of FEV₁1 decline seen in the study, which was lower than in previous COPD trials, may have been associated with the widespread use of corticosteroids and long-acting beta-agonists. Nearly two-thirds of patients were on a long-acting beta-agonist and/or an inhaled corticosteroid at baseline, increasing to three-quarters by the end of the study. This may explain the lack of impact on FEV₁ decline compared to the control group in the tiotropium group as a whole, they said. A sub-group analysis showed the rate of FEV₁ decline was significantly lower (p=0.046) in the 1554 tiotropium-treated patients who were not on inhaled corticosteroids or long-acting beta-agonists at baseline, compared with controls.

Patients treated with tiotropium showed a significant delay in time to first exacerbation, by an average of 4.1 months (p<0.001), as well as a significant 14% reduction in the number of exacerbations per patient-year (p<0.001). Additionally, tiotropium reduced the risk of exacerbations resulting in hospitalisation by 14% (p<0.002) compared to the control group.

The tiotropium-treated patients also showed an improvement in health-related quality of life, with an average score on the St George's Respiratory Questionnaire 2.3-3.3 units higher across the four years of the trial, compared to the control group.

Reporting the findings, Marc Decramer, Professor of Medicine and Chief of the Respiratory Division, Katholieke Universiteit Leuven, Belgium, and a lead investigator in the trial, said: "The unique trial design of UPLIFT reflects everyday treatment patterns and shows that tiotropium impacts of the clinical course of COPD, with sustained treatment benefits. It achieves improvement in lung function over time, although the rate of decline was not reduced. Tiotropium significantly reduces COPD exacerbations and improves survival." He predicted that the positive findings would lead to COPD being treated earlier in the course of the disease and more aggressively.

Safety results showed the rate of myocardial infarction was 27% lower in patients treated with tiotropium than in the control group (67 patients vs 85; relative risk 0.73; 95% CI, 0.53 to 1.00). There was no increased risk of stroke (relative risk 0.95). Respiratory failure was also less frequent in the tiotropium group (relative risk 0.67). The only adverse events more common with tiotropium were those consistent with its known safety profile, including dry mouth and constipation.

"This study reaffirms the safety profile for tiotropium, showing a reduction in cardiac morbidity and mortality and in respiratory failure," Professor Decramer concluded.

NEJM 2008; 359: 153-54.

Written by
Susan Mayor PhD
medical journalist, London, UK
susanmayor (at) mac.com
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