422
adrenocortical axis suppression in pre-
pubertal children. Fluticasone propi-
onate is a new ICS for the treatment of
asthma. It has a potent glucocorticoid
anti-inflammatory action with few sys-
temic effects
2
and is as efficacious as
beclomethasone dipropionate, even
when administered at half the dose.
2-4
Studies in adults with the use of simi-
lar doses,
5-7
and in children with mild
asthma receiving 400 μg/d,
8
comparing
FP and BUD showed them to be
equally effective. Differences in poten-
cy may be more important in children
with moderate to severe asthma re-
quiring high doses of ICS in whom a
lower effective dose might be associat-
ed with less likelihood of adverse ef-
fects. To determine whether FP in half
the dose was as efficacious and as safe
in controlling asthma as budesonide,
we assessed the effects of these drugs
in a group of prepubertal children with
moderate to severe chronic asthma.
The study was of randomized, double-
blind, double-placebo, parallel-group
design comparing the clinical efficacy
and safety/tolerability of daily FP, 400
μg, administered through a Diskus in-
haler (GlaxoWellcome) with BUD,
800 μg, administered through a Tur-
buhaler inhaler (Astra Pharma Inc),
both dry powder formulations.
Inhaled corticosteroids have an impor-
tant role in the treatment of chronic
asthma in children.
1
Despite the avail-
ability of several formulations, their ef-
E
Efficacy and safety of high-dose inhaled steroids in
children with asthma: A comparison of fluticasone
propionate with budesonide
Alexander C. Ferguson, MD, Sheldon Spier, MD, Ahmed Manjra, MD, Florens G. A. Versteegh, MD,
Stephen Mark, BSc, RT, and Paul Zhang, MSc
ficacy relative to each other has not
been widely studied, nor has the risk of
long-term adverse effects, especially on
growth and hypothalamo-pituitary-
From the B.C. Children’s Hospital, Vancouver, British Columbia, Canada; Alberta Children’s Hospital, Calgary,
Alberta, Canada; Westville Hospital, Durban, South Africa; Groene Hart Ziekenhuis, Gouda, Netherlands; and
Glaxo Wellcome Inc, Mississauga, Ontario, Canada.
Submitted for publication Aug 5, 1998; revision received Nov 16, 1998; accepted Dec 15, 1998.
Reprint requests: Alexander C. Ferguson, MD, University of British Columbia, B.C. Children’s
Hospital, 4480 Oak St, Vancouver, BC, V6H 3V4, Canada.
Copyright © 1999 by Mosby, Inc.
0022-3476/99/$8.00 + 0 9/21/96626
BDP Beclomethasone dipropionate
BUD Budesonide
FEV
1
Forced expiratory volume in 1 second
FP Fluticasone propionate
ICS Inhaled corticosteroid
PEF Peak expiratory flow
Objective: To compare the efficacy and adverse effects of inhaled flutica-
sone propionate (FP), 400 μg/d, with those of budesonide (BUD), 800 μg/d,
in children with moderate to severe asthma.
Methods: Three hundred thirty-three children, ages 4 to 12 years, receiv-
ing inhaled corticosteroids were enrolled in a double-blind, double-dummy,
randomized, parallel-group study. After a 2-week run-in phase, 166 chil-
dren received FP and 167 received BUD for 20 weeks. The primary out-
come variable was mean morning peak expiratory flow; the 2 treatments
were to be regarded as equivalent if the 90% CI for the treatment difference
was within ± 15 L/min. Pulmonary function, height, and diary cards were
assessed at each visit; and morning serum cortisol levels were determined
before and after treatment.
Results: Baseline peak expiratory flow was similar, FP 236 ± 72 (SD)
L/min and BUD 229 ± 74, increasing after treatment to 277 ± 41 and 257 ±
28, a difference between treatments of 12 L/min (90% CI 6-19 L/min; P =
.002). Symptom control and use of rescue medication were the same. Corti-
sol levels after treatment were 199 nmol/L (FP) and 183 nmol/L (BUD)
(treatment ratio = 1.09; 90% CI 0.98-1.21; P = .172). Linear growth was less
in those receiving BUD (mean difference, 6.2 mm; 95% CI 2.9-9.6; P =
.0003).
Conclusion: FP at half the dose was superior to BUD in improving peak
expiratory flow and comparable in controlling symptoms. Growth was re-
duced with BUD compared with FP, but there was no difference in serum
cortisol suppression or hepatic or renal function. (J Pediatr 1999;134:422-7)