A talk given in 2014 on the use of formoterol budesonide as SMART or single inhaler therapy in asthma

1. Emerging Evidence with Formoterol/ Budesonide as
SMART therapy in achieving guidelines based asthma
control
Dr. Aditya Jindal
Interventional Pulmonologist & Intensivist
Jindal Clinics
SCO 21, Sec 20D, Chandigarh
DM Pulmonary and Critical Care Medicine (PGI Chandigarh)

2. Definition of bronchial asthma (GINA 2014)
• Asthma is a heterogeneous disease, usually characterized by chronic
airway inflammation
• It is defined by the history of respiratory symptoms such as wheeze,
shortness of breath, chest tightness and cough that vary over time
and in intensity, together with variable expiratory airflow limitation

3. Asthma management cycle

4. STEP 1 STEP 2 STEP 3 STEP 4 STEP 5
Reliever:
SABA
Reliever:
SABA
Reliever:
SABA / Formoterol containing ICS (Low)
Controller:
Low ICS
Controller:
Low ICS
Add On:
LTRA or
Low dose
theophylline
Controller:
Low ICS +
LABA or
Med/High
ICS
Add On:
LTRA or
Low dose
theophylline
Controller:
Med/High
ICS + LABA
Add On:
LTRA or
Low dose
theophylline
Controller:
As Step 4
Add On:
• As in Step 4
• Anti-IgE
• Bronchial
Thermoplasty
• Sputum guided
treatment
• Oral steroids
Environmental control, Education, Written Action Plan
Regularly Assess:
• Asthma Control
• Asthma triggers
• Spirometry /PEFR
• Watch inhaler technique
• Ensure adherence
• Treat comorbidities
Asthma Pharmacotherapy

5. 8 am 8 pm
ICS + LABA
1-2 puffs
ICS + LABA
1-2 puffs
SABA
1-2 puffs
SABA
1-2 puffs
Fluticasone + Salmeterol
Budesonide + Formoterol
Salbutamol or
Levosalbutamol
80% asthmatics
2014
Current treatment with ICS/LABA
combination for moderate to severe asthma
Symptoms
Night time awakenings
Lung function
Activities and QoL
Exacerbations
Asthma control

6. Asthma Treatment: The Purple View
Time
Asthma signs
Maintain
Regular dosing
Achieve
regular dosing
1 × 2 1 ×2
500 250

7. 2014

8. GOAL study
Patients achieving control at the end of 1 year
Am J Respir Crit Care Med 2004; 170: 836-44
30% do not achieve a good level of control;
needed relievers and experienced exacerbations
In a recent study of > 600 patients who began combination
therapy, 10-14% needed oral steroids in the first 6 months

9. Completely
controlled,2%
Wellcontrolled,
29%
Somewhat
controlled,60%
Poorlycontrolled,
7%
Notcontrolled at
all, 2%
Patients’ perception of
Asthma Control
Partly controlled,
60%
Uncontrolled,
40%
GINA defined Asthma
Control
0% had controlled asthma
31 % patients felt had well
controlled or completely
controlled asthma

10. Status of Asthma Control in India: Unmet
needs of today
• 0% of asthma patients in India achieved guideline-defined asthma control
• 66% of asthma patients in India report exacerbations in the previous year
• 83% of Indian asthma patients report using rescue medication in the
previous month, the highest in the Asia-Pacific region
Respirology. 2013 Aug; 18(6):957–967

11. Proportion of patients reporting rescue and controller
medication use in previous
month

12. Asthmatics Overuse Relievers to Control Symptoms

13. Current Asthma Control is poor in
Indian Patients
Need interventions to improve

14. Single Inhaler Therapy (SIT)
• SMART – single inhaler for maintenance and reliever therapy in
asthma
• Formoterol plus ICS delivered by a ‘good’ device
• Provides additional anti-inflammatory therapy (ICS) and rapid
symptom relief (formoterol) during symptomatic periods
• Enables patient to rapidly adjust the ICS during the warning phase of
the exacerbation, while offering effective and rapid relief from
symptoms

15. 8 am 8 pm
ICS + Form
1-2 puffs
ICS + Form
1-2 puffs
ICS + Form
1 puff
ICS + Form
1 puff
Budesonide + Formoterol
Same inhaler as Controller Medication as
well as reliever medication
2014

16. Asthma Management : RED View

18. Formetrol is Long Acting Bronchodilator

19. In subjects with moderate asthma who use ICS regularly,
inhaled Budesonide caused a transient dose-dependent
vasoconstriction in the airway, thereby reversing one
manifestation of airway inflammation. These results
suggest that a pure controller medication can have
immediate beneficial effects not paralleled by changes in
airflow.
Effects observed at 60-90 minutes
Immediate anti-inflammatory effects of Inhaled
Budesonide in Patients with Asthma
(Mendes ES et al, Annals of American Thoracic Society
2014; 11: 706-711)

20. Increasing ICS Frequency can Achieve more Control in
Unstable Asthma
-10
0
10
20
30
40
Toogood et al: JACI 1982
400 800 1600
-200
-150
-100
-50
0
50
100
150
400 800 1600
Change in PEF L/min Change in Blood Eosinophils cells/mm3
Daily ICS dose in doubling steps (mg)
ICS given as 4 doses
ICS given as 2 doses
ICS given as 4 doses
ICS given as 2 doses

21. Budesonide-Formoterol can replace SABA, thus
ensuring simultaneous ICS with every puff

22. Synergy in SMART approach

23. Mean FEV1 over time
2.1
2.3
2.5
2.7
1 (-0.5) 2 (0) 3 (1) 4 (4) 5 (8) 6 (12)
Visit number (month)
After visit 2
Budesonide-formoterol+as-needed:
Bud/form + Terbutaline
Budesonide-formoterol+
terbutaline
p=0.0001
p=0.043
p=0<0001
Bud/form + Formoterol
Budesonide-formoterol SMART
Mean
FEV
1
(L)
Lancet 2006368:744-53

24. SMART: do patients ‘feel’ relief with FB Rescue
?
Patients have confirmed that they feel relief from breathlessness within the
first minute of taking the puff
Pulmonary Pharmacology & Therapeutics 19 (2006) 139–147

25. SMART to achieve Optimum Asthma Control
(7 Studies performed in Over 16,500 patients)

26. Better Asthma control with SMART

27. Why to prevent an exacerbation?
Exacerbations activate pathways of inflammation and remodeling resulting in deterioration of
lung function. Accelerated loss of lung function in turn puts patients at increased risk of
recurrent exacerbation resulting in a vicious cycle that may promote the exacerbation prone
phenotype
Clin Exp Allergy 2009; 39(2): 193–202
Accelerated loss in lung function due to
exacerbation can be up to 30.2 ml / year decline
in FEV1 after one severe exacerbation annually

28. 2/3rd asthmatics in India suffered
Exacerbations in past 12 months

29. Indians fear asthma exacerbations the most

31. 100
80
60
40
20
0
-15 -5
-10 5
0 10 15
%
change
from
day
–14
value
Day
Rescue ß2-agonist
Morning PEF
Night time symptoms
Tattersfield AE et al: AJRCCM 1999
425 severe exacerbations
Asthma Exacerbations in FACET Trial
Rescue medication usage increases
Morning PEFR decreases
Night time symptoms increase
approx. 5 days before the full-blown exacerbation (i.e. Day 0) when the
oral steroids treatment is initiated.
Evolution of an exacerbation- the clinical picture

32. 100
80
60
40
20
0
-15 -5
-10 5
0 10 15
%
change
from
day
–14
value
Day
Rescue ß2-agonist
Morning PEF
Night time symptoms (most
specific indicator)
Tattersfield AE et al: AJRCCM 1999
Opportunity?
Oral Steroids – Too Late!
425 severe exacerbations
Asthma Exacerbations in FACET Trial
Can exacerbation be prevented?

34. 0
20
40
60
80
100
120
ICS 800 µg bid
+ placebo qid
ICS 100 µg bid
+ ICS 200 µg qid
ICS 100 µg bid
+ placebo qid
Foresi et al., Chest 2000
Number of days using oral
steroids over 6 months
Management of Asthma Exacerbations:
Early Intervention with Increased Doses of ICS
***
***

35. SMART gives Extra ICS when needed most

36. 36% , p= 0.0012
52% , p< 0.001
17% , p= 0.43
28% , p= 0.52
Bud/form reduces the risk of future exacerbations versus all
conventional treatments such as ICS and ICS+LABA as
controllers and SABA as relievers
Eur Respir J 2011; 38: 584–593

37. Exacerbations leading to hospitalizations & ER
treatment are reduced with SMART

38. All at Lesser dose of Steroids

39. More well controlled & Less Uncontrolled
Asthmatics in SMART

40. Is
SMART
safe
for
patients
in
Severe
Exacerbations
If SMART
regimen
leads to
delays in
patients
seeking
medical
care
during
severe
asthma
exacerbati
ons
Increasing use of budesonide–
formoterol during worsening
asthma with the SMART
regimen does not lead to
greater delay in seeking medical
help

41. Adjustable Maintenance Dosing

43. SMART with Formeterol + Budesonide achieves Targets of
Asthma control in 21st Century

44. Does
SMART
work
in
our
population
too
?
Inadequately controlled asthmatic patients with bud/form maintenance and
reliever therapy, significant improvement in patients’ asthma control and
reductions in asthma symptoms and as-needed medication use was observed

45. Medication
Use
Maintenance
+ prn SABA
Adjusted
Maintenance
+ prn SABA
Maintenance
+ prn Bud-Form
BHR, eosinophils
or symptoms
(all with action plans)
One inhaler:
Maintenance & relief
Rapid adjustments in
controller replacing
SABA
No adjustment in
controller
Guided adjustment in
maintenance therapy
Use of FB for asthma control with 3 different
approaches

46. Stepwise treatment (GINA 2014)
Single inhaler therapy

47. Take home message
• Single inhaler therapy (SIT)
• It is the approach rather than the device which is more important
• Any device that does not require extra effort and has good lung
deposition should do the job
• SIT approach should be adopted as the standard of care for asthma
management