asthma-symbicort smart mar 2013
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asmaaaTRANSCRIPT
A A NNew ew AApproach to pproach to AAsthma sthma MManagementanagement
Handoko MDHandoko MD
Pulmonary and Respiratory Medicine Division Pulmonary and Respiratory Medicine Division
Department of Internal MedicineDepartment of Internal Medicine
dr. Ramelan Navy Hospital, Surabayadr. Ramelan Navy Hospital, Surabaya
World asthma prevalence
Estimated 300 million affected individuals worldwideEstimated 300 million affected individuals worldwide
The global prevalence of asthma in children and The global prevalence of asthma in children and adults ranges from 1-18% of the population adults ranges from 1-18% of the population
in different countries in different countries
The percentage of children reported The percentage of children reported to have had asthma increased significantly to have had asthma increased significantly
The increases prevalence in The increases prevalence in Africa, Latin America and Asia Africa, Latin America and Asia indicate that global burden of asthma indicate that global burden of asthma
is continuing to rise is continuing to rise
Annual worldwide deaths from asthma Annual worldwide deaths from asthma have been estimated at 250,000 have been estimated at 250,000
Chronic inflammatory disorder of the airways in which many cells and cellular elements play a role.
The chronic inflammation causes an associated increase in airway
hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest thightness,
and coughing, particularly at night or in the early morning.
These episodes are usually associated with widespread but variable airflow obstruction that is often reversible
either spontaneously or with treatment.
Definition Definition (GINA, 20(GINA, 201212))
Many cells and mediators are involved in asthma Many cells and mediators are involved in asthma and have several effects in the airways and have several effects in the airways (Barnes, 2004)(Barnes, 2004)
Inflammatory cells
Mast cellsEosinophilsTh2 cellsBasophylsNeutrophilsPlatelets
Structural cells
Epithelial cellsSmooth muscle cellsEndothelial cellsFibroblastsNerves
Mediators
HistaminesLeukotrienesProstanoidsPAFKininsAdenosineEndothelinsNitric oxideCytokinesChemokinesGrowth factors
Effects
BronchospasmPlasma exudationMucus secretionAHRStructural changes
Pathology of asthma (Barnes, 2004)
The Pathophysiology of asthmaThe Pathophysiology of asthma (Barnes, 2004)(Barnes, 2004)
The participation of several interacting inflammatory cells results in The participation of several interacting inflammatory cells results in acute and chronic inflammatory effects in the airwayacute and chronic inflammatory effects in the airway
Factors the development & expression of asthma Factors the development & expression of asthma (GINA, 20(GINA, 201212))
Host factorsHost factors
GeneticGenetic Genes pre-disposing to atopyGenes pre-disposing to atopy
Genes pre-disposing to airway Genes pre-disposing to airway hyperresponsivenesshyperresponsiveness
ObesityObesity
SexSex
Environmental Environmental factorsfactors
AllergensAllergens
Indoor: Indoor: Domestic mites, furred animals (dog, Domestic mites, furred animals (dog, cats, mice), cockroach allergen, fungi, cats, mice), cockroach allergen, fungi, molds, yeastsmolds, yeasts
Outdoor: Outdoor: Pollens, fungi, molds, yeastsPollens, fungi, molds, yeasts
Infections (predominantly viral)Infections (predominantly viral)
Occupational sensitizersOccupational sensitizers
Tobacco smoke (passive & active smoking)Tobacco smoke (passive & active smoking)
Outdoor/indoor air pollutionOutdoor/indoor air pollution
DietDiet
controlled
partly controlled
uncontrolled
exacerbation
Level of controlLevel of control
maintain and find lowest controlling step
consider stepping up to gain control
step up until controlled
treat as exacerbation
Treatment of actionTreatment of action
TREATMENT STEPSREDUCEREDUCE INCREASE
STEP1
STEP2
STEP3
STEP4
STEP5
RED
UC
EIN
CR
EA
SE
Asthma education
Environment control
As needed SABA
As needed SABA
Controller options
Select one Select one Add one or more
Add one or both
Low dose inhaled ICS
Low-dose ICS + LABA
Medium-dose ICS +
LABA
Oral glucocorticoi
d (lowest dose)
Leukotriene modifier
Medium / high-dose ICS
Leukotriene modifier
Anti-IgE treatment
Low dose ICS + leukotriene
modifierTheophylline
SRLow dose ICS + Theophylline SR
Step 1 Step 2 Step 3 Step 4 Step 5
Reduce Increase
What are the current asthma management goals?
Global Initiative for Asthma (GINA) guidelines state that asthma management should: prevent asthma exacerbations achieve and maintain control of symptoms maintain pulmonary function as close to normal
as possible maintain normal activity levels, including exercise prevent asthma mortality avoid adverse effects from asthma medications
GINA 2012
The challenges of asthma management
Over-reliance on rescue medication1 Suboptimal control1
Poor adherence to maintenance therapy1
Lack of clinical evidence to support the benefit of doubling ICS dose during worsenings2
Complexity of current treatments1
Lack of education and understanding among patients1
1FitzGerald JM, et al. Can Resp J 2006;13:253–259; 2Harrison TW, et al. Lancet 2004;363:271–275.
What is Symbicort® SMART™?
Symbicort® SMART™
Patients take a regular daily maintenance dose of Symbicort®, with additional inhalations if needed to provide rapid symptom relief and improved control
Patients do not require a separate SABA
Symbicort® SMART™ is an asthma management approach using only one inhaler where the underlying inflammation is treated with every inhalation, even when used as-needed
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Maintenance and reliever therapy in one inhaler
Symbicort® SMART™ provides maintenance and reliever therapy
in ONE inhaler
Daily maintenance dose, and Reliever use if needed for rescue
A separate rescue inhaleris not required
Budesonide(anti-inflammatory therapy that acts within hours)
Formoterol(rapid relief and long-acting bronchodilation)
Balanag VM, et al. Pulm Pharm Ther 2006;19:139-147Balanag VM, et al. Pulm Pharm Ther 2006;19:139-147
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Optimised dailymaintenance dose
Symptom relief
Conventional approach
Symbicort® SMART™
Optimised dailymaintenance dose
Symptom relief 1 and a timely increase
in anti-inflammatorytherapy
Symbicort® SMART™ is a new approach to asthma management
1. Balanag VM, et al. Pulm Pharm Ther 2006;19:139-1471. Balanag VM, et al. Pulm Pharm Ther 2006;19:139-1472. Gibson et al, Am J Respir Crit Care Med 2001;163:32-362. Gibson et al, Am J Respir Crit Care Med 2001;163:32-36
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Why is maintenance and reliever therapy possible with Symbicort® ?
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Time after drug administration (minutes)
3.50
3.90
3.82
3.74
3.66
3.58
–5 0 30 60 90 120 180150
Serum K+ (mmol/l)FEV1 (% from baseline)
Symbicort® 1280/36 µg (n = 55)
Salbutamol 1600 µg (n= 48)
–5 0 30 60 90 120
5
15
25
35
45
150 180
Symbicort® is as effective and well tolerated as salbutamol in treating acute asthma
Balanag VM, et al. Pulm Pharm Ther 2006;19:139–147.
NS
P = 0..66
NS
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Symbicort® is a rapid-acting reliever
Symbicort® 160/4.5 µg 1 inhalation
Sal/Flu 50/250 µg 1 inhalation
*P < 0.001 Symbicort® vs Sal/Flu at both 3 min and 15min
*
25
10
5
2
–50 5 10 15
% increase in FEV1
Time (minutes)
15
20
*
Placebo 1 inhalation
Palmqvist M, et al. Pulm Pharm Ther 2001;14:29–34.
Onset of action of Symbicort® vs Fluticasone/Salmeterol in stable asthma
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Symbicort® SMART™ vs fixed combination or higher ICS doses
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2–4 x Budesonide + SABA
Symbicort® + SABA
Symbicort® SMART™
Symbicort® SMART™ reduces the rate of severe exacerbations requiring medical
intervention
Events/patient/year
***P < 0.001 vs both Symbicort + SABA and 2–4 x Budesonide + SABA
STEAM1 mild to moderate
STEP3 moderate to severe
STAY2
moderate
0
0.1
0.2
0.3
0.4
0.5
0.6
***
***
***
1Rabe KF, et al. Chest 2006;129:246–256; 2O’Byrne PM, et al. Am J Respir Crit Care Med 2005;171:129–136;
3Scicchitano R, et al. Curr Med Res Opin 2004;20:1403–1418.
0.35
0.08
0.350.4
0.19
0.330.18
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Symbicort® SMART™ vs higher fixed doses of combination
treatments
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6-month double-blind, double-dummy
COMPASS study design
Sal/Flu 25/125 µg 2 inhalations bid + Bricasma® as reliever n=1123
Symbicort® 320/9 µg 1 inhalation bid + Bricasma® as reliever n=1105
Symbicort® 160/4.5 µg 1 inhalation bid + Symbicort® as reliever (SMART™) n=1107
Visit: 1 2 3 4 5
Week: –2 0 8 16 24
Regular ICS ≥ 500 µg R
Enrolled: n=4399
Randomised: n=3335
Run-in
Kuna P, et al. Int J Clin Pract 2007:61(5) :725-36
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Symbicort® SMART™ reduces the exacerbation rate compared to fixed dose combinations + SABA
P < 0.001
Symbicort® SMART™ reduces the rate of exacerbations by: 39% vs Sal/Flu + SABA 28% vs Symbicort® + SABA
0.20
0.15
0.10
0.05
0400 60 80 100 120 140 16020
Days since randomisation
P = 0.0048
NS
Sal/Flu + SABA Symbicort® + SABA Symbicort® SMART™
Exacerbations/patients
Kuna P, et al. Int J Clin Pract 2007:61(5) :725-36
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0
20
40
60
Sal/Flu + SABA Symbicort® + SABA Symbicort® SMART™
Similar improvements in daily asthma control
Asthma control days (%)
Run-in Treatment Run-in Treatment Run-in Treatment
NS
Asthma control days = symptom & rescue free days
5.7
43.7
5.9
42.2
5.8
41.3
Kuna P, et al. Int J Clin Pract 2007:61(5) :725-36
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COMPASS study conclusion
Symbicort® SMART™ vs higher fixed doses of Symbicort® or Salmeterol/Fluticasone +SABA : prolongs time to first severe exacerbation reduces number of severe exacerbations
All treatments provide similar improvements in daily asthma control
All treatments are well tolerated
Kuna P, et al. Int J Clin Pract 2007:61(5) :725-36
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Symbicort® SMART™
Regular maintenancebudesonide
Regular maintenanceformoterol
As-needed formoterol• rapid symptom relief²• reduces neutrophilic inflammation³ • prevents exacerbations
As-needed budesonide• anti-inflammatory effect within
hours¹• reduces eosinophilic inflammation¹ • prevents exacerbations
Symbicort® Maintenance And Reliever Therapy
¹Gibson et al, Am J Respir Crit Care Med 2001, Gibson et al, Am J Respir Crit Care Med 2001, ²Balanag VM, et al. Pulm Pharm Ther 2006;19:139-147 ³Maneechotestesuwan et al, Chest 2005;128:1936-1942
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Who is Symbicort® SMART™ suitable for?
Symbicort® SMART™ is SUITABLE for:
Patients who are not controlled on existing ICS therapy
or
Patients already controlled on both inhaled corticosteroids and long-acting beta2-agonists
Symbicort Product Information 2007
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Symbicort ®SMART™ treatment plan
Take Symbicort®
every dayFor maintenance
1. Take one doseevery morning
2. Take one doseevery evening
If needed:
Take an extra dosefor relief (repeatif necessary)
Symbicort Symbicort ®® Product Information 2007 Product Information 2007
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Will Symbicort® SMART™ lead to overuse of steroids?
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Symbicort® SMART™ reduces corticosteroid load compared to fixed-dose combinations + SABA
Level of use1
Seretide50/250 µg bid
(n=1123)
Symbicort320/9 µg bid
(n=1105)
Symbicort SMART160/4.5 µg bid + prn
(n=1107)
Mean inhaled corticosteroid dose (µg/day)
Not adjusted (FP vs BUD) 500 640 483
BDP equivalents* 1000 1000 755
Oral corticosteroid use/group
Total no. of events 148 139 86
Total days with event 1132 1044 619
FP, fluticasone propionate; BUD, budesonide; prn, as needed;
*BDP (beclomethasone dipropionate) equivalents adapted from GINA guidelines 2006.
Observations from the COMPASS study
Kuna P, et al. Int J Clin Pract 2007:61(5) :725-36
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Symbicort® SMART™ is well tolerated
Several large clinical trials have demonstrated that: Symbicort® SMART™ is well tolerated Symbicort® SMART™ is associated with a
low incidence of candidiasis or dysphonia
O’Byrne PM, et al. Am J Respir Crit Care Med 2005;171:129–136; Rabe KF, et al. Lancet 2006;368:744–753; Vogelmeier C, et al. Eur Respir J 2005;26:819–828; Rabe KF, et al. Chest 2006;129:246–256; Scicchitano R, et al. Curr Med Res Opin 2004;20:1403–1418; Kuna P, et al. Int J Clin Pract 2007:61(5) :725-36
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Symbicort® SMART™ in 2012 Global Initiative for Asthma (GINA)
“If a combination inhaler containing formoterol and budesonide is selected, it may be used for both rescue and maintenance.”
“Both components of budesonide-formoterol given as needed contribute to enhanced protection from severe exacerbations in patients receiving combination therapy for maintenance and provide improvements in asthma control at relatively low doses of treatment.”
“The benefit in preventing exacerbations appears to be the consequence of early intervention at a very early stage of a threatened exacerbation…”
GINA 2012
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Other statements about Symbicort® SMART™
“In the context of rescue therapy with budesonide/formoterol, this could prevent the evolution of an acute exacerbation by suppressing the increase in inflammation, thus resulting in marked reduction in the number of mild and severe exacerbations.”
Barnes PJ, ERJ 2007;29:587-595Barnes PJ, ERJ 2007;29:587-595* Single inhaler therapy=maintenance and reliever therapy. Single inhaler therapy=maintenance and reliever therapy.
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Treats the underlying inflammation with every inhalation
Reduces exacerbations1–6
Improves daily asthma control 1–5
Reduces overall steroid load 1–6
Is simple to use with only one inhaler for maintenance and relief
1O’Byrne PM, et al. Am J Respir Crit Care Med 2005;171:129–136; 2Rabe KF, et al. Lancet 2006;368:744–753; 3Vogelmeier C, et al. Eur Respir J 2005;26:819–828; 4Rabe KF, et al. Chest 2006;129:246–256; 5Scicchitano R, et al. Curr Med Res Opin 2004;20:1403–1418; 6. Kuna P, et al. Int J Clin Pract 2007:61(5) :725-36
Symbicort® SMART™
vs ICS or ICS/LABA+SABA:
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Handoko & Peter J Barnes 2012
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