Newly released details from a safety trial that was stopped early reveal that respiratory-related deaths or life-threatening events occurred four times as often among blacks who took Serevent than among blacks who did not take the drug.
There was no significant difference in deaths or serious adverse outcomes among whites who did and did not take the asthma drug, which is manufactured by GlaxoSmithKline, a WebMD sponsor.
The findings, first reported to the U.S. Food and Drug Administration in 2003, led the regulatory agency to require a black-box warning on the labeling for Serevent and the similar GlaxoSmithKline asthma drug Advair.
The warning notes that use of the drug in the study led to a "small but significant increase in asthma-related deaths." A separate box also states, "Data from this study further suggests that the risk might be greater in African-American patients."
Thirteen deaths occurred among 13,176 study participants treated with Serevent for 28 weeks, compared with three deaths among 13, 179 participants who did not take the drug.
Seven of the 13 deaths in the Serevent arm of the study involved blacks, even though blacks made up just 18% of the total study population.
Both Serevent and Advair contain the active ingredient salmeterol, but Advair also contains an inhaled corticosteroid. Results from the Salmeterol Multicenter Asthma Research Trial (SMART) appear in the January issue of the journal Chest.
Drug Treats Symptoms Only
Serevent is in a class of drugs known as long-acting beta-agonists, which treat the symptoms of asthma but not the inflammation that causes it.
For this reason, long-acting beta-agonists are now only recommended for asthma patients who are already on an inhaled corticosteroid to reduce inflammation and treat the underlying cause of their condition.
Harold S. Nelson, MD, who led the research team, tells WebMD that the apparent racial difference among the study population is probably not due to genetic or other physiologic differences between blacks and whites.
Instead, he says he believes that economically disadvantaged blacks in the study may have had poorer control of their underlying disease.
A disproportionate number of black patients who died or had life-threatening asthma-related events in the study were not taking an inhaled corticosteroid.
Nelson is a professor of medicine at Denver's National Jewish Medical and Research Center. He is also a consultant and speaker for GlaxoSmithKline, which funded the study.
"In the patients who were not on inhaled corticosteroids, [Serevent] may have relieved their symptoms but masked their worsening asthma," he says.
Close Monitoring Important
Steven E. Gay, MD, served on the FDA advisory panel that reviewed the safety of the long-acting beta-agonists last summer. The panel recommended that Serevent, Advair, and the Schering-Plough drug Foradil continue to be sold in the United States.
Gay tells WebMD that much has changed in the understanding of how different asthma drugs should be used since the SMART trial was halted in 2003. He directs the pulmonary and critical care medicine unit at the University of Michigan Health System.
"At that time, the role of inhaled corticosteroids in asthma was still being evaluated," Gay tells WebMD. "It is now extremely clear that this is the first-line treatment for asthma. No other treatments, including long-acting beta-agonists, address the underlying disease. They help patients feel better by relieving the symptoms."
He says the long-acting beta-agonists are excellent drugs for the treatment of patients who do not get adequate asthma relief with inhaled corticosteroids alone. But they should not be used without inhaled steroids for the treatment of asthma.
Gay says it is too soon to say if Serevent and other long-acting beta-agonists pose a special risk to blacks. Researchers are attempting to answer the question.
"These drugs clearly still have a role in the treatment of asthma," he says. "I monitor my African-American patients who are on the drugs closely for changes in their asthma, as I do all my patients who take them."
A spokeswoman for GlaxoSmithKline tells WebMD that the company continues to stand behind Serevent as a treatment for asthma.
"Serevent is approved as safe and effective," Patty Johnson says. "All medicines have a risk/benefit profile that should be weighed by physicians. But GlaxoSmithKline continues to stand firmly behind Serevent. Serevent exhibits a favorable benefit-to-risk profile and is an important treatment for asthma and chronic obstructive pulmonary disease (COPD)."