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Low-Dose Theophylline Highly Effective for Asthma
Control
Martha Kerr
Oct. 28, 2003 (Orlando) — Low-dose theophylline is highly
effective in controlling asthma without adverse effects, according
to investigators with the American Lung Association Asthma Clinic
Research Centers (ALA ACRC). A secondary finding in the
Effectiveness of Low-Dose Theophylline as Add-On Theophylline in the
Treatment of Asthma (LODO) trial is that the drug appears to be
antagonistic when taken with inhaled corticosteroids, resulting in a
worsening of lung function.
Charles G. Irvin, PhD, who is also affiliated with the University
of Vermont at Burlington, presented results of the study here to
attendees of CHEST 2003, the annual meeting of the American College
of Chest Physicians.
The study involved 488 patients with poorly controlled asthma who
were randomized to one of three treatment arms: placebo,
theophylline 300 mg daily at bedtime, or montelukast 10 mg daily at
bedtime in addition to their currently prescribed suboptimal
treatment regimens. Study duration was six months.
"Theophylline fell out of favor in the 1970s because of the
introduction of long-acting bronchodilators...and because of its
narrow therapeutic index. It was poorly tolerated and hard to
achieve the right dose," Dr. Irvin told Medscape. In this study, the
investigators used half the dose that was typically used 30 or 40
years ago.
"There was no effect on acute asthma exacerbations but there was
a significant effect on lung function," Dr. Irvin reported.
Theophylline improved both pre- and postbronchodilator
FEV1, while montelukast only improved prebronchodilator
FEV1.
The incidence of adverse effects was similar in all three
treatment arms and had disappeared completely within three months,
including the nausea and nervousness reported most frequently in the
two active treatment arms.
"We were surprised that montelukast had little effect, but these
patients were from a broad group," Dr. Irvin said. "Also, the theory
was that theophylline was synergistic with corticosteroids.... Our
data suggest the opposite."
About a quarter of patients in the montelukast and theophylline
arms were receiving inhaled corticosteroids at baseline. In patients
randomized to montelukast, there appeared to be no interaction with
inhaled corticosteroids. In the group receiving theophylline,
measures of lung function deteriorated. The data suggest, Dr. Irvin
told Medscape, that theophylline and inhaled corticosteroids are
antagonistic. "This is absolutely intriguing," he said.
"This study shows that low-dose theophylline might be a very
effective therapy for asthma in lieu of inhaled corticosteroids,"
Dr. Irvin noted. "This could be huge news for the third world or for
inner cities," as the cost of theophylline is a fraction of that of
montelukast.
"Back in the '70s, doctors were using double the dose of
theophylline [that was used in this study]...the drug was poorly
tolerated and it fell out of favor.... In this study, all side
effects had disappeared within three months.... This could change
clinical practice," Dr. Irvin asserted.
"We don't normally give theophylline for these patients. We
normally try inhalation therapy with steroids and bronchodilators,"
said Hans L. Hahn, MD, FCCP, of the Deutsche Klinik fur Diagnostics
in Wiesbaden, Germany. "But it is cheap, long-acting and it may work
for patients who don't want to use inhalation therapy."
"The thing is to get [theophylline] blood levels," Dr. Hahn told
Medscape. "But if you can't get the patient in for blood levels or
don't have access to a lab, you can still use [theophylline]?You go
by how it works. If it works and there are no side effects, then
you're probably all right."
"I have a different take on Dr. Irvin's study," Katharine Knobil,
MD, clinical associate professor of medicine at the University of
North Carolina at Research Triangle Park, told Medscape. Dr. Knobil
is also an employee of GlaxoSmithKline. She was a presenter of a
separate study during the late-breaking science sessions.
"Only a fraction of patients in this study were on inhaled
steroids. That's one of the first things that a patient [with
asthma] should be given," Dr. Knobil pointed out.
"There are some benefits with low-dose theophylline," she
continued, "but there are so many other drugs with fewer side
effects that we can use."
CHEST 2003: Late-breaking science sessions. Presented Oct. 28,
2003.
Reviewed by Gary D. Vogin, MD
Martha Kerr is a freelance writer for
Medscape.
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