Boehringer Ingelheim and Pfizer have released a new analysis of 30 rigorously controlled clinical trials confirming the long term safety profile of Spiriva (tiotropium). The new and expanded safety data contradicts the conclusions about tiotropium in an article by Singh et al. published in the 24 September issue of the Journal of the American Medical Association. Both companies considered it important to release these data to ensure doctors have the most comprehensive, up-to-date safety information on tiotropium in order to make the best treatment decisions for their patients.
Because COPD patients (Chronic Obstructive Pulmonary Disease) have in general a higher cardiovascular risk than the average population, cardiovascular safety in a COPD medication is of critical importance. Therefore Boehringer Ingelheim has put special emphasis on the broad investigation of Spiriva including its cardiovascular safety.
The latest analysis of 30 placebo-controlled double-blind, randomized trials with data from 19,545 COPD patients (tiotropium 10,846; placebo 8,699), conducted by Boehringer Ingelheim demonstrated that there is no increased risk of death (all-cause) or death due to cardiovascular events in patients treated with Spiriva specifically:
"We strongly disagree with the conclusion reached by Singh et al. We have disclosed to regulatory authorities worldwide this important information which is part of a very robust analysis of all our double-blind, placebo-controlled, parallel group trials with a duration of at least four weeks. Our analysis, which includes data from the four-year UPLIFT trial, supports the safety profile of Spiriva," commented Dr Andreas Barner, vice chairman of the Board of Managing Directors at Boehringer Ingelheim, responsible for Research, Development and Medicine. "Patients and physicians can be confident that Spiriva is a safe and effective medication. In clinical trials and since its introduction, we have collected extensive safety data adding up to an exposure of more than 10 million patient years."
Peer-reviewed meta-analyses of aggregate published data like Singh et al1 have their appropriate place in scientific research. However, these analyses have well-recognised limitations, such as combining study summaries rather than analyzing individual patient data, or not correcting for patients who dropped out of trials early.
Most of the evidence in the analysis by Dr Singh and colleagues is contributed by a single study, the Lung Health Study, involving a different anticholinergic medication, (ipratropium). In this study most of the cardiovascular deaths occurred among patients who were not using their medication. Other limitations include the inability to adjust for treatment duration and accounting for patients who discontinue the trial early, apparent double-counting of trials and combining placebo and active comparator drugs in the control group.
The integrated safety data presented includes data from the UPLIFT (Understanding Potential Long-term Impacts on Function with Tiotropium) trial, a study that includes mortality as a pre-specified endpoint. UPLIFT one of the largest COPD trials ever undertaken, involved 5,993 COPD patients from 37 countries around the globe over a four-year treatment period. Patient safety during the trial was closely followed by an independent Data Safety Monitoring Board.
The complete results of the UPLIFT trial will be presented on October 5, 2008 during the European Respiratory Society 2008 Annual Congress in Berlin.
Spiriva, a long-acting inhaled anticholinergic medication, is the first inhaled treatment to provide significant and sustained improvements in lung function with once-daily dosing.
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies.
Founded in 1849, Pfizer is the world`s largest research-based pharmaceutical company taking new approaches to better health.