Professional Documents
Culture Documents
Methods
Patients
Results
Study population
Characteristic
CIC 160 lg
once daily*
Patients (n)
416
Age (yr)
Median (range)
9 (611)
Height (cm)
Median (range)
135 (112169)
Mean s.d.
135.5 10.9
Sex (male/female, %)
63/37
1.53 0.38
Mean FEV1, l s.d.
Mean FEV1, % predicted s.d.
77 10
20 8.8
Mean reversibility: change in
FEV1, % s.d.
Mean PEF fluctuation, % s.d.
14 9
Severity of asthma based on GINA/NIH guidelines, n (%)
Intermittent
11 (3)
Mild persistent
29 (7)
Moderate persistent
158 (38)
Severe persistent
218 (52)
ICS pretreated/non-ICS pretreated,
219 (53)/197 (47)
n (%)
Asthma symptom score sum (mean)
1.62
BUD 400 lg
once daily
205
9 (611)
137 (112164)
136.8 10.9
65/35
1.58 0.38
78 10
21 8.9
12 8
5 (2)
12 (6)
73 (36)
115 (56)
100 (49)/105 (51)
1.66
Asthma symptoms and use of rescue medication. Ciclesonide 160 lg once daily and budesonide 400 lg once daily achieved statistically
signicant improvements in asthma symptom
score sum after 12 wk of treatment ()1.18 and
)1.19, respectively, ITT; )1.21 and )1.21,
respectively, PP; all p < 0.0001 vs. baseline,
two-sided). The improvement in asthma symptom score sum was not signicantly dierent
between treatment groups (ITT: 95% CI: )0.14
to 0.21, p 0.8379, two-sided; PP: 95% CI:
)0.20 to 0.25, p 0.8868, two-sided). Ciclesonide and budesonide treatment also achieved a
statistically signicant reduction in the need for
rescue medication after 12 wk of treatment (ITT:
)1.58 and )1.64 pus/day, respectively;
p < 0.0001 vs. baseline). The improvement in
use of rescue medication was not signicantly
dierent between treatment groups (ITT: 95%
CI: )0.26 to 0.29 pus/day, p 0.8593, twosided).
The percentage of days without asthma
symptoms and without need for rescue medication was 73% and 70% for patients in the
ciclesonide 160 lg once daily and budesonide
400 lg once daily treatment groups, respectively, and there were no dierences between
treatment groups (ITT). The percentage of
nocturnal awakening-free days was 98.5% in
both treatment groups (ITT).
The percentage of patients with asthma exacerbations was small in both treatment groups
(2.6% and 1% in the ciclesonide 160 lg once
daily and budesonide 400 lg once daily treatment groups, respectively), and no signicant
between treatment dierence in the time-to-onset
of the rst asthma exacerbation was observed.
Quality of life
PP
1529
1566
1526
1556
232 12
<0.0001
250 17
<0.0001
220 13
<0.0001
253 18
<0.0001
)19
)59 to 22
0.8158
)33
)75 to 10
0.9347
1.838
1.891
1.838
1.879
0.207 0.014
<0.0001
0.230 0.019
<0.0001
0.204 0.015
<0.0001
0.236 0.020
<0.0001
)0.024
)0.068 to 0.021
0.8531
)0.032
)0.079 to 0.015
0.9106
202.1
204.6
199.3
201.2
22.7 2.0
<0.0001
25.0 2.8
<0.0001
22.5 2.2
<0.0001
26.3 3.0
<0.0001
)2.3
)8.9 to 4.3
0.7551
)3.7
)10.9 to 3.4
0.8491
215.1
221.0
211.2
216.7
14.6 1.9
<0.0001
11.3 2.7
<0.0001
14.5 2.1
<0.0001
14.9 2.8
<0.0001
3.3
)3.0 to 9.6
0.1537
)0.4
)7.0 to 6.3
0.5411
Changes in body height. Baseline height measurements in the total population are provided in
Table 1. For the stadiometry subgroup, there
were 58 children in the ciclesonide group and 26
in the budesonide group, with similar numbers of
children aged 69 and 1011 yr across the two
treatment groups. Baseline mean s.d. height
396
24-H urinary cortisol adjusted for creatinine. Treatment with ciclesonide 160 lg once
daily and budesonide 400 lg once daily resulted
in statistically signicant decreases ()2.17 and
)5.16 nmol/mmol creatinine, respectively, in 24h urinary cortisol adjusted for creatinine after
12 wk of treatment, amounting to median percentage decreases of )6.9% and )22.9%, respectively; both p < 0.0001 vs. baseline; Fig. 3). The
decrease in 24-h urinary cortisol was signicantly
greater in the budesonide group compared with
the ciclesonide group (dierence between ciclesonide and budesonide treatment groups
2.989 nmol/mmol creatinine; p < 0.0001, onesided).
Fig. 3. Change in 24-h urinary cortisol adjusted for creatinine after 12 wk of treatment with ciclesonide (n 353) or
budesonide (n 179) (intention-to-treat population). Urine
samples with creatinine values in the normal range were
included. Ciclesonide 160 lg is a delivered dose, equivalent
to a nominal dose of 200 lg. Data are presented as least
squares mean standard error of the mean p < 0.0001 vs.
baseline for both groups. *p-Value vs. budesonide is onesided. CIC, ciclesonide; OD, once daily; BUD, budesonide.
References
1. Global Initiative for Asthma. Global Strategy for
Asthma Management and Prevention 2006. Available at
www.ginasthma.com. Accessed 2006.
2. Fuhlbrigge AL, Davis KJ, Guilbert T, Spahn J,
Peden D. Children and asthma in America 2004 survey.
J Allergy Clin Immunol 2005: 115: S589.
3. Poulos LM, Toelle BG, Marks GB. The burden of
asthma in children: an Australian perspective. Paediatr
Respir Rev 2005: 6: 207.
4. Sennhauser FH, Braun-Fahrlander C, Wildhaber
JH. The burden of asthma in children: a European
perspective. Paediatr Respir Rev 2005: 6: 27.
5. Georgitis JW. The 1997 Asthma Management Guidelines and therapeutic issues relating to the treatment of
asthma. National Heart, Lung, and Blood Institute.
Chest 1999: 115: 2107.
6. National Asthma Education and Prevention Program.
Expert Panel Report: guidelines for the diagnosis and
management of asthma update on selected topics
2002. J Allergy Clin Immunol 2002: 110: S141219.
7. British Guideline on the Management of Asthma: a
National Clinical Guideline. Available at www.brit_
thoracic.org.ule. Last accessed 2006.
8. Allen DB. Systemic eects of inhaled corticosteroids in
children. Curr Opin Pediatr 2004: 16: 4404.
9. Gillissen A. Managing asthma in the real world. Int J
Clin Pract 2004: 58: 592603.
10. Williams LK, Pladevall M, Xi H, et al. Relationship
between adherence to inhaled corticosteroids and poor
outcomes among adults with asthma. J Allergy Clin
Immunol 2004: 114: 128893.
11. Mealy NE, Baycs M, Castaner J. Ciclesonide: treatment of allergic rhinitis antiallergy/antiasthmatic.
Drugs Future 2001: 26: 10339.
12. Richter K, Kanniess F, Biberger C, Nave R,
Magnussen H. Comparison of the oropharyngeal
deposition of inhaled ciclesonide and uticasone propionate in patients with asthma. J Clin Pharmacol 2005: 45:
14652.
13. Nave R, Fisher R, Zech K. In vitro metabolism of
ciclesonide in human lung and liver precision-cut tissue
slices. Am J Respir Crit Care Med 2003: 167: A1510.
14. Nave R, Bethke T, van Marle S, Zech K. Pharmacokinetics of [14C] ciclesonide after oral and intravenous
administration to healthy subjects. Clin Pharmacokinet
2004: 43: 47986.
15. Rohatagi S, Luo Y, Shen L, et al. Protein binding and
its potential for eliciting minimal systemic side eects
with a novel inhaled corticosteroid, ciclesonide. Am J
Ther 2005: 12: 2019.
16. Nave R, Gunawardena KA, Zech K, Bethke TD.
Pharmacokinetic disposition of inhaled ciclesonide and
its metabolite desisobutyryl-ciclesonide in healthy subjects and patients with asthma are similar. Int J Clin
Pharmacol Ther 2006: 44: 17.
17. Newman S, Salmon A, Nave R, Drollmann A. High
lung deposition of 99mTc-labeled ciclesonide administered via HFA-MDI to patients with asthma. Respir
Med 2006: 100: 37584.
18. Gelfand EW, Georgitis JW, Noonan M, Ruff ME.
Once-daily ciclesonide in children: ecacy and safety in
asthma. J Pediatr 2006: 148: 37783.
19. Pedersen S, Garcia Garcia ML, Manjra A, Theron
I, Engelstatter R. A comparative study of inhaled
ciclesonide 160 microg/day and uticasone propionate
399
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
400
176 microg/day in children with asthma. Pediatr Pulmonol 2006: 41: 95461.
Skoner D, Maspero J, Kundu S, Lloyd M, Banerji D.
Ciclesonide, administered once daily, has no eect on
growth velocity in prepubertal children with mild, persistent asthma. J Allergy Clin Immunol 2006: 117: S11.
Pearlman DS, Berger WE, Kerwin E, Laforce C,
Kundu S, Banerji D. Once-daily ciclesonide improves
lung function and is well tolerated by patients with
mild-to-moderate persistent asthma. J Allergy Clin
Immunol 2005: 116: 120612.
Juniper EF, Guyatt GH, Feeny DH, Ferrie PJ,
Griffith LE, Townsend M. Measuring quality of life
in children with asthma. Qual Life Res 1996: 5: 3546.
Selroos O, Pietinalho A, Lofroos AB, Riska H.
Eect of early vs late intervention with inhaled corticosteroids in asthma. Chest 1995: 108: 122834.
Dluhy RG. Clinical relevance of inhaled corticosteroids and HPA axis suppression. J Allergy Clin Immunol
1998: 101: S44750.
Shapiro G, Bensch G, Lanier R, et al. Once-daily
treatment with ciclesonide is eective and well-tolerated
in children with persistent asthma. J Allergy Clin
Immunol 2005: 115: S6.
Pulmicort Turbohaler 400. The Electronic Medicines Compendium. Available at: http://emc.medicines.org.uk/, accessed 2007.
Selroos O, Edsbacker S, Hultquist C. Once-daily
inhaled budesonide for the treatment of asthma: clinical
evidence and pharmacokinetic explanation. J Asthma
2004: 41: 77190.
Alvesco 160 Inhaler. The Electronic Medicines Compendium. Available at: http://emc.medicines.org.uk/,
accessed 2007.
Postma DS, Sevette C, Martinat Y, Schlosser N,
Aumann J, Kafe H. Treatment of asthma by the
inhaled corticosteroid ciclesonide given either in the
morning or evening. Eur Respir J 2001: 17: 10838.
Chapman KR, Patel P, DUrzo AD, et al. Maintenance of asthma control by once-daily inhaled ciclesonide
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.