Symbicort - the budesonide component
Inhaled corticosteroids are first
line maintenance therapy
Laitinen LA, et al. J Allergy Clin Immunol 1992;90(1):32-42
LAA / ICS rationale
Early intervention with budesonide in
children provides long-term improvement
in lung function
FEV1
% change from
baseline
Budesonide (N = 216, age = 3-11yrs)
Controls (N = 62, age = 3-11yrs)
40
30
***
20
10
***p<0.001
0
-10
0
0.5
1
1.5
2
2.5
3
3.5
Treatment duration (years)
Agertoft L, et al. Respir Med 1994;88:373-81
Budesonide
Early intervention with budesonide is
associated with greater subsequent
improvement in lung function in children
Annual change in %
predicted FEV1
n = 216
p = 0.02 for correlation
12
10
8
6
4
2
0
<2
2–3
3–5
>5
Asthma duration at start of budesonide (years)
Agertoft L, et al. Respir Med 1994;88:373-81
Budesonide
Budesonide, 400µg once daily significantly
improved evening PEF compared to 200 µg
twice daily in children
Change in PEF
(L/min)
N = 167
30
25
Age = 5-12 yrs
p = 0.01
20
15
10
Week 4
5
Week 8
0
Budesonide
400 µg
once daily
Budesonide
200 µg
twice daily
Campbell LM, et al. Int J Clin Pract 1998;52:213-9
Budesonide
A similar reduction in bronchodilator usage
was seen in children receiving either 400g
once daily or 200g twice daily
N=167
Age=5-12 years
ß2-agonist use per day
(no. of actuations)
2.5
Budesonide
Turbuhaler®
400 µg once
daily evening (n=71)
2.0
1.5
Budesonide
Turbuhaler®
200 µg twice
daily (n=86)
1.0
0.5
0
Baseline
Week 4
Week 8
Campbell LM, et al. Int J Clin Pract 1998;52:213-9
Each group vs
baseline p=0.0001
Budesonide
Budesonide once daily is as effective as
budesonide twice daily in protecting against
exercise induced bronchoconstriction
Budesonide Turbuhaler®
Maximum % fall in FEV1
30
Baseline
12 weeks
25
20
N = 57
Mean age = 9.7
years
15
10
5
0
200 µg
once daily
100 µg
twice daily
100 µg
once daily
Jónasson G, et al. Pediatr Allergy Immunol 2000;11:120-5
Placebo
Budesonide
Adjusting the dose of budesonide to respond
to a sudden deterioration is effective in
controlling asthma in children
Percent of
children
N =150
Age=1-14 years
50
40
Initial dose of budesonide =
800 - 1,600 g/day,
reducing to 400 g/day
over 4 - 8 days
30
20
10
0
<1
1 to 2
2 to 3
>3
Mean time from onset of treatment
to control of exacerbation (Days)
Volovitz B, et al. Clin Pediatr (Phila) 2001;40(2);79-86
Budesonide
Long-term growth in children is
unaffected by budesonide
Mean daily dose of budesonide
decreased from 710 to 430 g
during the treatment period
Height SDS
0.2
0
-0.2
-0.4
-0.6
-0.8
-1
Controls (n = 62, age = 3 -11 yrs)
Budesonide (n = 216, age = 3 -11 yrs)
Run-in
-2 -1.5 -1 -0.5 0
0.5 1
1.5
2
2.5
3
3.5
Time (years)
Agertoft L et al. Respir Med 1994;88:373-81
Budesonide
Final adult height is unaffected by
budesonide in children
Measured target height (cm)
200
190
Boys
180
Girls
170
Mean predicted = 172.9 cm
Mean measured = 173.2 cm
160
150
150
160
170
180
190
200
Predicted target height (cm)
Agertoft L et al. N Engl J Med 2000;343:1064-9
Budesonide
Bone mineral density (BMD) in children is
unaffected by budesonide
BMD
g/cm2
NS
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
n= 157
0.917 g/cm2
0.915 g/cm2
Control
Budesonide
(average daily dose
= 504 g for 3-6 years)
0.2
0.1
0
Agertoft L. Am J Respir Crit Care Med 1998;157:178-83
Budesonide
No effect on HPA-axis was seen in children
receiving budesonide over 12 weeks
Baseline
After 12 weeks
Plasma cortisol (mmol/litre)
600
ns
ns
ns
ns
Placebo
100 µg
200 µg
400 µg
500
400
300
200
100
0
Pulmicort Turbuhaler twice daily
Shapiro et al. J Pediatr 1998; 132:976-982.
Budesonide
Clinical trials have provided great
reassurance of the safety of budesonide
Clinical adverse events
>38,000 patients and healthy volunteers
>580 clinical trials
• no difference compared to placebo in type of event or
frequency
• No gender difference
• No particular pattern in children or adults
• No influence on final adult height
• No influence on bone density
Budesonide
Pulmicort® postmarketing exposure
• Pulmicort® first launched in 1982 as a pMDI.
• Pulmicort Turbuhaler® is marketed in 59 countries (first
launch 1989).
• The estimated exposures to Q3/2001 is more than 10
billion treatment days (Pulmicort Turbuhaler®
7.2 billion treatment days).
• 4041 received case reports.
Budesonide