Combination therapy with a long-acting beta-agonist and a leukotriene antagonist in moderate asthma.
BACKGROUND
Long-acting beta-agonists (LABAs) and inhaled corticosteroids administered together appear to be complementary in terms of effects on asthma control. The elements of asthma control achieved by LABAs (improved lung function) and leukotriene receptor antagonists (LTRAs; protection against exacerbations) may be complementary as well.


OBJECTIVE
We sought to determine whether the combination of the LTRA montelukast and the LABA salmeterol could provide an effective therapeutic strategy for asthma.


METHODS
In a randomized, placebo-controlled, crossover study of 192 subjects with moderate asthma, we compared the clinical efficacy of regular treatment over 14 weeks with the combination of montelukast and salmeterol to that with the combination of beclomethasone and salmeterol in moderate asthma. The primary efficacy outcome was time to treatment failure.


RESULTS
Three months after the randomization of the last subject, the Data and Safety Monitoring Board determined that the primary research question had been answered and terminated the trial. The combination of montelukast and salmeterol was inferior to the combination of beclomethasone and salmeterol as judged by protection against asthma treatment failures (p = 0.0008), lung function (26 L/min difference in a.m. peak expiratory flow rate, p = 0.011), asthma control score (0.22 difference in Asthma Control Questionnaire score, p = 0.038), and markers of inflammation and airway reactivity.


CONCLUSIONS
Patients with moderate asthma similar to those we studied should not substitute the combination of an LTRA and an LABA for the combination of inhaled corticosteroid and an LABA.
Deykin
Aaron
A
Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. Aaron.Deykin@biogenidec.com
Wechsler
Michael E
ME
Boushey
Homer A
HA
Chinchilli
Vernon M
VM
Kunselman
Susan J
SJ
Craig
Timothy J
TJ
DiMango
Emily
E
Fahy
John V
JV
Kraft
Monica
M
Leone
Frank
F
Lazarus
Stephen C
SC
Lemanske
Robert F
RF
Martin
Richard J
RJ
Pesola
Gene R
GR
Peters
Stephen P
SP
Sorkness
Christine A
CA
Szefler
Stanley J
SJ
Israel
Elliot
E
D000085:Acetates / Q000627:therapeutic use*; D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D003131:Combined Modality Therapy; D003521:Cyclopropanes; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011804:Quinolines / Q000627:therapeutic use*; D000068299:Salmeterol Xinafoate; D013440:Sulfides; D016896:Treatment Outcome
D000085:Acetates; D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D010919:Placebos; D011804:Quinolines; D013440:Sulfides; D000068299:Salmeterol Xinafoate; C093875:montelukast; D000420:Albuterol