A Comparison of Short-term Treatment with
Inhaled Fluticasone Propionate and Zafirlukast for
Patients with Persistent Asthma
Robert A. Nathan, MD, Eugene R. Bleecker, MD,
Chris Kalberg, PhD, and the Fluticasone Propionate Study Group
PURPOSE: To compare the short-term efficacy and safety of
low-dose fluticasone propionate with that of oral zafirlukast
therapy for patients previously treated with beta-2-agonists
alone, and to evaluate the potential therapeutic benefit of
switching from zafirlukast to a low-dose inhaled corticosteroid.
SUBJECTS AND METHODS: This study consisted of a 4-week
randomized, double-blind treatment period followed by a
4-week open-label period. Two hundred ninety-four patients
Ն12 years old with asthma previously uncontrolled with beta-
2-agonists alone were randomly assigned to treatment with low-
dose inhaled fluticasone (88
g twice daily) or oral zafirlukast
(20 mg twice daily). After 4 weeks, all patients discontinued
their double-blind therapy and received open-label fluticasone
(88
g twice daily). Outcomes included pulmonary function,
asthma symptoms, albuterol use, asthma exacerbations, and ad-
verse events.
RESULTS: During the double-blind treatment period, flutica-
sone patients had significantly greater improvements in morn-
ing peak flow (29.3 L/min vs. 18.3 L/min), percentage of symp-
tom-free days (19.8% vs. 11.6%), and daily albuterol use (Ϫ1.8
puffs per day vs. Ϫ1.1 puffs per day) compared with zafirlukast
patients (P Յ0.025, each comparison). During the open-label
treatment period, patients switched from zafirlukast to flutica-
sone experienced additional improvements in morning peak
flow (17.2 L/min), evening peak flow (13.6 L/min), and FEV
1
(0.11 liter) and daily albuterol use (Ϫ0.9 puffs daily) compared
with values obtained at the end of the double-blind treatment
period (P Յ0.001, each comparison).
CONCLUSION: Low-dose fluticasone was more effective than
zafirlukast in improving pulmonary function and symptoms in
patients with persistent asthma. In addition, switching patients
from zafirlukast to fluticasone further improved clinical
outcomes. Am J Med. 2001;111:195–202. ᭧2001 by Excerpta
Medica, Inc.
T
he recognition that asthma is a chronic inflamma-
tory disease has resulted in treatment guidelines
that emphasize the use of anti-inflammatory med-
ications for treating persistent asthma (1,2). Inhaled cor-
ticosteroids are recognized as the most effective anti-in-
flammatory agents available for treating asthma (1). The
clinical effects of inhaled corticosteroids extend beyond
improving traditional measures of efficacy. Studies have
shown that inhaled corticosteroid therapy reduces the
risk of hospitalization and death from asthma, reduces
costs associated with the disease, and improves quality of
life, and it may reduce airway remodeling (3–11). Fluti-
casone propionate is an inhaled corticosteroid drug with
greater efficacy and reduced oral bioavailability com-
pared with other inhaled corticosteroids (12–18). Fluti-
casone has been shown to improve pulmonary function
and symptom control of mild, moderate, and severe per-
sistent asthma (19,20).
Leukotriene modifiers, a relatively new class of drugs
for asthma treatment, inhibit the effects of endogenously
produced leukotrienes by either enzymatic inhibition of
leukotriene synthesis or receptor antagonism (21).
Zafirlukast, a leukotriene receptor antagonist, is ap-
proved for treating persistent asthma (22–24). Leuko-
trienes have bronchoconstrictive effects and also appear
to be proinflammatory, although the latter effect has not
yet been conclusively demonstrated in humans. Pub-
lished data regarding the anti-inflammatory effects of
leukotriene modifiers are somewhat limited, and there
are no data comparing the anti-inflammatory activity of
leukotriene modifiers with that of inhaled corticoste-
roids.
Supported by a grant from Glaxo Wellcome Inc., Research Triangle
Park, North Carolina.
From Asthma and Allergy Associates, P.C. (RN), Colorado Springs,
Colorado; Wake Forest University School of Medicine (ERB), Winston-
Salem, North Carolina; and Glaxo Wellcome Inc. (CK), Research Tri-
angle Park, North Carolina.
Requests for reprints should be addressed to Robert A. Nathan, MD,
Asthma and Allergy Associates, P.C., 2709 N Tejon Street, Colorado
Springs, Colorado 80907.
The following investigators participated in this study (Protocol
FLTA5001): Donald W. Aaronson, MD, Des Plaines, IL; James W.
Baker, MD, Portland, OR; Robert Berkowitz, MD, Atlanta, GA;
Jonathan Bernstein, MD, Cincinnati, OH; Michael Z. Blumberg, MD,
Richmond, VA; Paul Chervinsky, MD, North Dartmouth, MA; Arthur
C. Degraff, MD, Hartford, CT; Karen D. Dunn, MD, Raleigh, NC;
Thomas B. Edwards, MD, Albany, NY; Roger Fox, MD, Tampa, FL; Jay
Grossman, MD, Tucson, AZ; Phillip E. Korenblat, MD, St. Louis, MO;
Nicholas A. Nayak, MD, Normal, IL; Harold S. Nelson, MD, Denver,
CO; David S. Pearlman, MD, Aurora, CO; Andrew J. Pedinoff, MD,
Princeton, NJ; Lewis Smith, MD, Chicago, IL; Sheldon L. Spector, MD,
Los Angeles, CA; Julius H. Van Bavel, MD, Austin, TX; Suzanne Weak-
ley, MD, Houston, TX; John M. Weiler, MD, Iowa City, IA; Steven F.
Weinstein, MD, Huntington Beach, CA; Michael J. Welch, MD, San
Diego, CA; Mark Wencel, MD, Wichita, KS; and John Yarbrough, MD,
Gainesville, GA.
Manuscript submitted December 6, 2000, and accepted in revised
form May 15, 2001.
᭧2001 by Excerpta Medica, Inc. 0002-9343/01/$–see front matter 195
All rights reserved. PII S0002-9343(01)00800-2