When added to patients’ normal low doses of inhaled corticosteroids, the drug, tiotropium bromide, co-marketed by pharmaceutical companies Boehringer-Ingelheim and Pfizer under the trade name Spiriva®, was effective in increasing the number of days without symptoms and without need for a rescue inhaler in patients with otherwise poorly controlled symptoms.
Tiotropium bromide, as part of the anticholinergic class of drugs, is approved for use in COPD patients, but not yet for use in asthmatics. However, if the results can be replicated and a safety profile established in this new patient type, the drug may open up new options for treating asthmatics struggling for control of their symptoms.
The study, funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, is now available online in the New England Journal of Medicine and is scheduled to appear in an upcoming print issue.
“While many asthma patients do very well on a single inhaled corticosteroid medication, others still have persistent symptoms that prevent them from doing all the things they need to do in their daily lives,” said Stephen Peters, M.D., Ph.D., director of research for the Section of Pulmonary, Critical Care, Allergy & Immunologic Diseases at Wake Forest Baptist and lead author on the study. “They need something else to help control those symptoms and make life more livable. Tiotropium bromide, already being used by millions of COPD patients, may provide one more option for an effective ‘something else.’”
Conducted by the NHLBI’s Asthma Clinical Research Network, the study compared three treatment methods for poorly controlled asthmatics: doubling the dose of inhaled corticosteroids alone, supplementing a low dose of inhaled corticosteroids with a long-acting beta agonist (salmeterol), and supplementing a low dose of inhaled corticosteroids with a long-acting anticholinergic drug (tiotropium bromide). The study followed 210 adults whose asthma was not well-controlled on low doses of inhaled corticosteroids alone. Participants received each treatment for 14 weeks with two-week breaks in between, for a total of 48 weeks.
The researchers found tiotropium bromide to be an effective treatment using several asthma control measurements, including patients’ day-to-day lung function as well as the number of days in which they had no asthma symptoms and did not need to use their albuterol rescue inhalers. When patients began the trial, their average number of such “asthma control days” was 77 per year (extrapolated from shorter observation periods in the trial). Doubling corticosteroids gave patients another 19 symptom-free days per year on average, while adding tiotropium to low-dose corticosteroids gave them an additional 48 days.
Increasing inhaled corticosteroids or supplementing them with long-acting beta agonists like salmeterol are the two preferred treatment options available for adults whose asthma is poorly controlled on low doses of inhaled corticosteroids. However, higher doses of corticosteroids do not improve symptoms for all patients and can have significant side effects, while long-acting beta agonists have come under scrutiny for their risk of worsening asthma symptoms that could result in hospitalization and, rarely, death.
According to the study, adding tiotropium bromide to low doses of inhaled corticosteroids is more effective at controlling asthma than doubling inhaled corticosteroids alone, and as effective as adding the long-acting beta agonist salmeterol.
“Tiotropium relaxes smooth muscle in the airways through a different mechanism than beta agonists, and thus may help people who do not respond well to currently recommended treatments,” said Peters, associate director of the Center for Genomics and Personalized Medicine Research at Wake Forest Baptist. He explained that anticholinergics block a part of the autonomic nervous system that can cause airway muscles to contract. “The goal is to individualize therapy – to find the right treatment for the right patient. Further analysis of the study data will help us better understand which patients respond best to tiotropium.”
Longer-term studies are needed to establish the safety of tiotropium bromide for asthma patients and to determine its effect on the frequency and severity of asthma exacerbations, Peters said.
“Much research over the last century has explored the role of cholinergic mechanisms (which constrict the airways) and anticholinergic therapies in asthma. However, this is the first study to explore adding an anticholinergic inhaler to low-dose inhaled corticosteroids,” said James Kiley, Ph.D., director of the NHLBI’s Division of Lung Diseases. “The Asthma Clinical Research Network is designed to address exactly these kinds of practical and important management questions, with the ultimate goal of helping asthma patients.”
The NHLBI established the Asthma Clinical Research Network in 1993 to conduct multiple, well-designed clinical trials for rapid evaluation of new and existing therapeutic approaches to asthma and to disseminate laboratory and clinical findings to the healthcare community. In addition to Wake Forest Baptist, the clinical centers are: Brigham and Women’s Hospital, Boston; Columbia University, New York City; Duke University, Durham, N.C.; Galveston University of Texas Medical Branch, Galveston; National Jewish Health, Denver; University of California, San Diego; University of California, San Francisco; University of Wisconsin-Madison; Washington University School of Medicine, St. Louis. The data coordinating center is at Penn State College of Medicine in Hershey.