Embargoed for Release: May 22, 2001, 4:00 PM EDT
Embargoed for Release: May 22, 2001, 4:00 PM EDT
Researchers supported by the National Heart, Lung, and Blood Institute (NHLBI) today report findings from two studies that address an ongoing controversy about whether long-acting beta-agonists (LABs) should replace or supplement inhaled corticosteroids (ICS) in the treatment of adults with mild-to-moderate persistent asthma.
The scientists found that using LABs alone is not as effective as using ICS alone in treating adults with mild-to-moderate persistent asthma. However, when LABs are used regularly to supplement treatment with ICS, they can improve asthma control and enable substantial reductions in steroid doses.
The two studies are "Long Acting Beta-Agonist Monotherapy vs. Continued Therapy with Inhaled Corticosteroids in Patients with Persistent Asthma" and "Inhaled Corticosteroid Reduction and Elimination in Patients with Persistent Asthma Receiving Salmeterol," and they appear in the May 23, 2001 issue of the Journal of the American Medical Association.
According to NHLBI Director Dr. Claude Lenfant, "These two studies provide new and important scientific information about treatment questions that clinicians face every day in managing adult patients with mild-to-moderate persistent asthma: can they switch patients to long-acting beta-agonists from inhaled corticosteroids or use long-acting beta-agonists to reduce steroid doses? Now we have the answer."
Asthma is a chronic lung disease that currently affects more than 15 million Americans, approximately 40 percent of whom have moderate persistent asthma. It is currently estimated to cost the U.S. economy $12.3 billion a year in health care costs and lost productivity.
Asthma is due to an inflammatory process in the bronchial air passages of the lungs that causes narrowing of the airways and, if untreated, may result in gradual loss of lung function. The NHLBI's "Guidelines for the Diagnosis and Management of Asthma" recommend that clinicians use daily anti-inflammatory medications like ICS to reduce inflammation in patients with mild-to-moderate persistent asthma and that they add a LAB if low to moderate ICS doses do not adequately reduce asthma symptoms. Because patients have been concerned about the safety of ICS, some physicians have started treating them with LABs alone.
The two new studies show that using LABs alone is not effective for total asthma control.
The two studies were designed to investigate the usefulness of treating adults with mild-to-moderate persistent asthma with LABs instead of ICS or in addition to ICS. They shared a 6-week run-in phase during which all patients were treated with moderate doses of ICS. Following the run-in period, 164 patients with asthma that was well controlled with ICS were entered into the Salmeterol or Corticosteroid Study, while 175 patients whose asthma was not well controlled with ICS alone were enrolled in the Salmeterol + or - Inhaled Corticosteroid Study.
In the first study, patients were randomized into three groups to compare the effects of continuing the ICS alone, switching to a LAB, or switching to placebo. The study showed that patients treated with the LAB alone had nearly four times more treatment failures, nearly three times more exacerbations, and significantly greater increases in measures of airway inflammation.
In the Salmeterol + or - Corticosteroids Study, patients were treated with ICS alone or with ICS plus a LAB to see if adding the LAB would permit the ICS dose to be reduced or eliminated. The investigators found that the addition of the LAB permitted a 50 percent reduction in ICS dose without significant loss of asthma control. However, complete elimination of the ICS resulted in a 4.3 times higher risk of treatment failure.
The Salmeterol or Corticosteroids study also showed the importance of reviewing multiple measures of asthma outcomes to determine the most effective therapy. Although LABs alone were highly effective in improving some conventional measures of asthma outcomes, including averages in asthma symptom scores and rescue medicine use, they were not effective in preventing more serious outcomes, such as asthma attacks or treatment failures.
Said Lenfant, "The Salmeterol or Corticosteroid Study provides an important lesson about the outcomes that are commonly used to evaluate asthma treatments. While some outcomes may show that the patient feels better, those outcomes may not be the best indicators of what is happening in the lungs."
The two studies were conducted by the NHLBI's Asthma Clinical Research Network (ACRN), which was created in 1993 to facilitate rapid design and implementation of clinical trials to quickly evaluate new and existing asthma treatments. In the past eight years, ACRN has completed six clinical studies providing answers to important asthma treatment questions. The participating centers are: Brigham and Women's Hospital, Boston; Harlem Lung Center, New York City; National Jewish Medical and Research Center, Denver; University of Wisconsin, Madison; Jefferson Medical College, Philadelphia; and University of California, San Francisco. The data coordinating center is at the M.S. Hershey Medical Center, Hershey, PA.
The NHLBI Guidelines define mild-to-moderate persistent asthma as asthma that produces daily symptoms and/or nocturnal symptoms more than five times a month and/or requires medicines to reduce symptoms every day.
Medications and/or equipment were donated to the NHLBI and ACRN by Aradigm Corporation; Enact Health Management Systems; Glaxo Wellcome, Inc.; Hoechst Marion Roussel Inc.; Rhone-Poulence Rorer Pharmaceuticals, Inc.; and Sievers Instruments Inc.
For more information, contact the NHLBI Communications Office at 301-496-4236.