Proceeding to the Future of Asthma Therapy

Proceeding to the Future

of Asthma Therapy

Terry Wu 吳中隆吳中隆吳中隆吳中隆

AstraZeneca Taiwan

氣喘定義定義定義定義

1. 氣喘乃是一種呼吸道持續性的慢性發炎反應，且支氣管對於各種刺激，會產生過度反應 (遺傳體質加上外來過敏原)。

2. 反覆發作的氣流阻滯、會自行緩解或經適當治療而恢復。(可逆性的肺功能障礙)

3. 依嚴重程度，可出現：呼吸困難、哮嗚音、胸悶和咳嗽，尤其是在夜間或清晨，症狀更明顯、有些人會出現多痰。

SMART: Symbicort Maintenance And Reliever TherapryP.3AZT-SYMB-07082

Nov 13th, 2007

Current golden standard treatment manages

the two components of asthma separately*

Maintenance Inhaler

Daily use

Prevention

BronchoconstrictionBronchoconstrictionInflammationInflammation

`Rescue Inhaler

Rapid symptom relief

Does not address underlying inflammation

* Canadian Asthma Consensus Report., CMAJ; 1999


Nov 13th, 2007

1975

1980

1985

1990 19952000

Large use of short-acting

ß2-agonists

“Fear” of short-acting ß2-agonists

Single inhaler therapy

(Symbicort®)

ICS treatment introduced

1972

Adding LAßA to ICS therapyKips et al, AJRCCM 2000

Pauwels et al, NEJM 1997

Greening et al, Lancet 1992

Evolving Treatment Options

Bronchospasm Inflammation Remodelling


Nov 13th, 2007

Patients over-rely on SABAs vs. ICS;

irrespective of asthma severity

Rabe KF at al, Eur Respir J 2000; 16: 802-807


Nov 13th, 2007

Despite ICS or ICS/LABA maintenance, 74%

of patients used rescue therapy each day

SABA Use (puffs/day in last week)

0 10 20 30 40 50

9+

5-8

3-4

1-2

None

Nu

mber

of

inh

ala

tion

s

% of patients

Base: all patients (n=2,406)

Partridge MR at al, BMC Pulmonary Medicine 2006; 6:13


Nov 13th, 2007

Patients adjust their SABAs early and ICS too

late at the time of worsening symptoms

ICS & LABA

ICS no LABA

Seretide

Symbicort

0

1

2

3

4

5

At worst Recovery

Mean no. of puffs per day of SABA

Early adjustment

≥4-fold increase at

worst

When well

Signs/ warnings

Partridge MR at al, BMC Pulmonary Medicine 2006; 6:13

0

1

2

3

4

5

At worst Recovery

Mean no. of puffs per day of ICS

No early adjustment

≤2-fold increase at

worst

When well

Signs/ warnings

*


Nov 13th, 2007


Nov 13th, 2007


Nov 13th, 2007

Your suggestion is???


Nov 13th, 2007

Symbicort SMART

Symbicort Maintenance And Reliever Therapy

• It provides rapid symptom

relief and improved control

Symbicort 維持和緩解雙效療法維持和緩解雙效療法維持和緩解雙效療法維持和緩解雙效療法

Inflammation and Bronchoconstriction

• Patients do not require a

separate SABA


Nov 13th, 2007

What is SMART ？？？？


Nov 13th, 2007

SMART strategy is unique to Symbicort®

Budesonide

• Anti-inflammatory agent

• Fast onset within 3-5 hours

• Demonstrated dose response

• Greater efficacy in combination with formoterol vs. higher doses of budesonide alone

• Long-acting bronchodilator

• Onset as rapid as salbutamol(1-3 minutes)

• Demonstrated dose response 6 µg to 48 µg/day

Only Symbicort® can be

prescribed in this manner

+ Formoterol

SMART features


Nov 13th, 2007

Symbicort SMART has better efficacy over

fixed-dose combination at lower dose

Total daily medication use (maintenance and relief)

Fixed Symbicort+ prn SABA

Fixed Symbicort+ prn Symbicort

(Symbicort SMART)

If a combination inhaler containing formoterol and budesonide is selected, it may be used for both rescue and maintenance. This approach has been shown to result in reductions in exacerbations and improvements in asthma control in adults and adolescents at relatively low doses of treatment (Evidence A) … page60


Nov 13th, 2007

The underlying inflammation is treated with

every inhalation even when used as needed


Nov 13th, 2007

Symbicort SMART reduces asthma

exacerbation rates more effectively than fixed

combination

Exacerbations (events/100 patients/year)

* Extrapolated to one year from six month

result

23

32

38

0

10

20

30

40

Seretide 50/250 µg bid + SABA

Symbicort 320/9 µg bid + SABA

Symbicort SMART 160/4.5 µg bid + as needed

-39%

COMPASS: Kuna P et al, Int J Clin Prac. 2007; 61: 725-736

***

* P<0.001 vs. Seretide+ SABA

** P<0.01 vs. 2x Symbicort + SABA

• A six month double-blind study including 3,335 patients


Nov 13th, 2007

Symbicort SMART improves daily symptom

control*

Change in am PEF from run-in

7.9

10.6

15.3

p=0.004

p<0.001

5

10

15

20

0

-60

-50

-40

-30

-20

-10

0

Totalsymptom score Awakenings

p<0.001

p<0.001

p<0.05

p<0.01

* SMILE: Rabe KF et al, Lancet. 2006; 368: 744-753

Bricanyl Oxis SymbicortMaintenance Symbicort + as

needed:

• A one year double-blind study including 3,394 patients

+94%


Nov 13th, 2007

Symbicort SMART reduces the use of daily

reliever

Inhalations use/patient/24 hours

0.93

0.58

0

0.5

1

Seretide + SABA Symbicort SMART

COSMOS: Vogelmeier C et al, Eur Respir J. 2005; 26: 819-828

-38%

*

* P<0.001

• Maintenance dose of Seretide titrated on clinicians’ judgment to be either 2x50/100 µg; 2x50/250 µg or 2x50/500 µg

• Maintenance dose of Symbicort 160/4.5 µg; 1 or 2 puffs bid based on clinicians’ judgment

• One year randomized real life study including 2,143 patients


Nov 13th, 2007

Symbicort SMART reduces numbers of

hospitalizations and ER treatments

Hospitalizations/ER treatment (events/100

patients/year)

* Extrapolated to one year from six month

result

16

10 10

0

10

20





-39%

*

* P<0.01 vs. Seretide+ SABA



Nov 13th, 2007

Symbicort SMART reduces drug load of oral

corticosteroids

days with use of oral streoids

619

1044

1132

0

400

800

1200






-45%


Nov 13th, 2007

Formoterol provides not only rapid symptom

relief but also anti-inflammatory benefits

Time after drug administration (minutes)

0

5

10

15

20

25

30

0 5 10 15 20 25

FEV1 at 3 minutes after inhalation: p<0.001 for all active treatments compared with placebo

Mean FEV1

(% change from baseline)

Formoterol 9 µg

Formoterol 4.5 µg

Salbutamol 200 µg

Salbutamol 450 µg

Placebo

Seberova E et al, Respiratory Medicine 2000; 94(6): 607 - 611

0

500

1000

1500

2000

2500

Formoterol

P<0.01

Neutrophil count (x103/mm3) P<0.005

P<0.5

Placebo BudesonideBaseline 4 weeks Baseline 4 weeks Baseline 4 weeks

Maneechotesuwan et al, CHEST 2005; 128(4): 1936-1942

rapid symptom relief


Nov 13th, 2007

Budesonide has anti-inflammatory effect much

faster than we thought it’d be

Placebo

Budesonide 800 µg

Time (hours)

FEV1 (L)

-2 -1 0 1 2 3 4 5 6 7 8 9 10

4

3

2

1

*****

0

Treatment at the start of the late response

* p<0.05

Paggiaro PL et al, Am J Crit Care Med 1994;149:1447–51.

rapid symptom relief

Sputu

m e

osin

ophils

(%)

60

50

40

30

20

10

0

Placebo

Budesonide

Eosinophils

p<0.05

Gibson P et al: Am J Respir Crit Care Med 2001; 163: 32-36

Single dose of budesonide(2,400 µg) within 6 hours


Nov 13th, 2007

Balanag V.M et al, Pulm Pharm Thera 2006;

19(2): 139-147prn Symbicort


Nov 13th, 2007

Symbicort is as effective and well tolerated as

salbutamol in treating acute asthma

Balanag VM et al, Pulm Pharm Thera 2006; 19(2): 139-147

prn Symbicort


Nov 13th, 2007

Timing is more important than overall dosage

Number of days using oral steroids over 6 months

0

20

40

60

80

100

120

p<0.001

Budesonide 100 µg bid + placebo qd

Budesonide 100µg bid +budesonide 200µg qd

Budesonide 800 µg bid + placebo qd

Foresi A et al, CHEST 2000; 117(2): 440-446

It is the timing of the increase in ICS dose, resulting from as-needed use of budesonide/formoterol to treat symptoms, rather than the total inhaled dose of ICS that improves efficacy.

O’Byrne PM et al, J Allergy Clin Immuno 2007; 119: 1332-1336

Prof. O’Byrne is the member of GINA scientific committee


Nov 13th, 2007

Symbicort Maintenance And Reliever Therapy

Symbicort 維持和緩解雙效療法維持和緩解雙效療法維持和緩解雙效療法維持和緩解雙效療法

Symbicort SMART license has been received on Sep 26th, 2007

Symbicort® Turbuhaler® 160/4.5μg/dose (Budesonide/formoterol)

衛署藥輸字第023265號

….. B. 以吸必擴®作為氣喘症之維持和緩解療法

成人和青少年（12歲及以上）：一般維持劑量是每天一般維持劑量是每天一般維持劑量是每天一般維持劑量是每天1111次次次次，，，，每次吸入每次吸入每次吸入每次吸入2222劑劑劑劑；；；；或每天或每天或每天或每天2222次次次次，，，，每次吸入每次吸入每次吸入每次吸入1111劑劑劑劑。有些病人可能需要使用每天2次，每次吸入2劑的維持劑量。病患應視症狀需求而增加吸入劑量，但單次使用不得吸入超過單次使用不得吸入超過單次使用不得吸入超過單次使用不得吸入超過6666劑劑劑劑。。。。每日可在短每日可在短每日可在短每日可在短時間內使用最高可至共時間內使用最高可至共時間內使用最高可至共時間內使用最高可至共12121212劑之總劑量劑之總劑量劑之總劑量劑之總劑量。

一般原則

為緩解症狀而增加吸入劑數的病人，如果在2222週內週內週內週內，氣喘控制情況仍未見改善，應考慮重新評估氣喘的治療。成人和青少年每日通常不需要吸入每日通常不需要吸入每日通常不需要吸入每日通常不需要吸入8888劑以上劑以上劑以上劑以上。特殊情況下，成人和青少年每日可在短時間內最高吸入可在短時間內最高吸入可在短時間內最高吸入可在短時間內最高吸入12121212劑劑劑劑。


Nov 13th, 2007

Symbicort SMART means more effective

treatment, yet simpler

Current treatment plan Symbicort SMART

P.28AZT-SYMB-07082

Nov 13th, 2007

P.29AZT-SYMB-07082

Nov 13th, 2007

How to use Turbuhaler®

1.旋轉並移去瓶蓋

2. 一手拿直瓶身,另一手推底盤,先向右再向左轉到底,聽到“卡嚓”一聲,即填藥完成

3. 先請吐氣,含住吸嘴後深深快速地吸飽一口氣,閉氣5秒後,輕輕且慢慢的吐氣,即完成一次吸入動作勿對著藥瓶吐氣

4. 將瓶蓋旋轉歸位

不要忘了漱口

P.30AZT-SYMB-07082

Nov 13th, 2007

Turbuhaler® – checking dose


Nov 13th, 2007

One or many?

or

Which treatment would you choose?Which treatment would you choose?


Nov 13th, 2007

謝謝聆聽

Documents

Proceeding to the Future of Asthma Therapy