Transcript New Therapeutic Options for COPD - Site Title

Prepared by: Christine Liew (F0158)
Preceptor: Lee Chuey Ee



Chronic Obstructive Pulmonary Disease
(COPD) is characterized by progressive,
partially reversible airflow obstruction,
associated
with
an
enhance
chronic
inflammatory response in the airways.
It is a preventable and treatable respiratory
disorder.






Preventing disease progression
Reduce frequency and severity of
exacerbations
Reduce patient’s symptoms
Improve exercise tolerance
Improve lung function and general health
Improve quality of life
1.
a)
b)
c)
d)
e)
2.
3.
Bronchodilators
Inhaled short-acting β2-agonist (SABA)
Inhaled short-acting anticholinergics (SAAC)
Inhaled long-acting β2-agonist (LABA)
Inhaled long-acting anticholinergics (LAAC)
Methylxanthines
Corticosteroids
Phosphodiesterase-4 (PDE4) inhibitors
1.
2.
3.
4.
5.
6.
7.
SABA : Fenoterol and Salbutamol
SAAC: Ipratropium
LAAC: Tiotropium
Inhaled corticosteroid (ICS): Fluticasone,
budesonide, beclomethasone
Combinations of LABA and ICS:
Salmeterol/ fluticasone,
formeterol/budesonide
Systemic corticosteroid: Prednisolone
Methylxanthines: Theophylline


1. Tiotropium
Restricted usage in the hospital. Only 100
patients approved to receive subsidized
treatment.
2. Patients still having multiple exacerbations
despite on treatment. Current therapy is
insufficient to adequately control COPD.


-
-
Class: Long-acting β2-agonist (LABA)
Mechanism of Action (MOA):
Stimulate intracellular adenyl cyclase which is
responsible for catalyzing the conversion of
adenosine triphosphate (ATP) to cyclic
adenosine monophosphate (AMP).
Increased AMP levels cause relaxation of
bronchial smooth muscles.


This review comprises of four placebocontrolled clinical studies of indacaterol
treatment in patients with moderate-tosevere COPD.
Details on the studies is shown in the next
slide.
1.
2.
3.
4.
Clinical diagnosis of moderate-to-severe COPD
Aged 40 years and above
Smoking history of at least 20 packs/year
Exclusion criteria:
-Had recent chest infection or had been
hospitalised for an exacerbation or respiratory
infection in the 6 weeks before screening
- History of asthma
- Patient with clinically significant condition that
might compromised their safety eg unstable
ischemic heart disease, uncontrolled
hypertension, uncontrolled diabetes
1.
2.
3.
4.
5.
6.
7.
Mean duration of COPD from diagnosis of 7 years
Mean smoking history of 40-57 packs per year
Mean age of 63-64 years old
More males (52-80%) than females
Patients are allowed to be on ICS, provided the dose
and regimen remain unchanged.
Spirometry measurements at baseline showed an
FEV1 of 53–56% predicted and FEV1/FVC ratio of
0.51–0.53 (both values assessed within 30 min
after inhalation of salbutamol 400 μg).
Concomitant cardio- or cerebro-vascular conditions
were present in 20% of patients, hypertension in
50%, diabetes mellitus in 10%, and hyperlipidaemia
in 35%.
Figure 1: Bronchodilator effect (FEV1) of
Treament
Figure 2: Effect of Treatment on Breathlessness
(assessed using transition dyspnoea index
[TDI] )
Figure 3: Effect of Treatment on Use of asneeded Salbutamol
Figure 4: Effect of Treatment on COPD
Exacerbation Rate
1.
2.
3.
4.
Indacaterol is an once-daily LABA with a rapid
onset of action (within 5 minutes), a peak effect
at approximately 3 hours, and a duration of
bronchodilation lasting at least 24 hours.
One of its attraction is its once-daily dosing as
compared to the other twice-daily dosing
bronchodilators. It might improve adherence.
It provides a level of bronchodilation that is
similar to tiotropium but greater than the
twice-daily agents, formoterol and salmeterol.
Indacaterol has a good safety profile.
5.
6.
Indacaterol is an effective and beneficial
maintenance bronchodilator treatment for
patients with moderate-to-severe COPD.
Indacaterol would be a reasonable first
choice for maintenance bronchodilator
therapy.


-
-
Class: PDE-4 inhibitor
Mechanism of Action (MOA):
Selectively inhibit PDE-4 enzyme, thus
preventing the breakdown of cAMP which
plays an important role in regulating
inflammatory cell activity.
Consequently,
result
in
reduced
inflammation.


There are 4 clinical trials which will be
discussed.
Details on the trials are shown in the next
slide.
1.
2.
3.
Roflumilast is the first selective PDE4 inhibitor
approved in Europe as an add-on antiinflammatory therapy in patients with symptomatic
severe COPD with frequent exacerbations.
From the clinical trial data, it is shown that
roflumilast improves lung function and reduces
exacerbation rates in COPD compared with placebo.
When used as an add-on treatment to concomitant
bronchodilator
therapy,
roflumilast
shows
significant and sustained improvement in lung
funtion as compared to placebo.
4.
5.
6.
Significant
adverse
effects
of
PDE4
inhibitors includes nausea, diarrhoe, weight
loss and headache.
Data should be collected to determine the
long-term safety of roflumilast.
In conclusion, more studies are needed to
solidifies roflumilast place in COPD therapy.
7.
Other important areas for further research
includes thorough evaluations of the
potential synergies and additive effects of:
• roflumilast and ICS therapy
• roflumilast versus ICS/theophylline as
add-on therapy to long-acting
bronchodilators.
1.
2.
3.
4.
5.
6.
7.
Global Initiative for Chronic Obstructive Lung Disease (GOLD).
Global Strategy for the Diagnosis, Management and Prevention of
Chronic Obstructive Pulmonary Disease. UK; 2011.
Clinical Practice Guidelines: Management of Chronic Obstructive
Pulmonary Disease. Ministry of Health Malaysia. 2nd;2009.
Micromedex
Paul W Jones, Neil Barnes, Claus Vogelmeier, David Lawrence,
Benjamin Kramer. Efficacy of Indacaterol in the Treatment of
Patients with COPD. Primary Care Respiratory Journal. UK; 2011.
Marcos Ribeiro, Kenneth R Chapman. Comparative Efficacy of
Indacaterol in COPD. International Journal of COPD. Canada; 2012.
David Price, Alison Chisholm, Dermot Ryan, Alan Crockett, Rupert
Jones. The Use of Roflumilast in COPD: a primary care perspective.
Primary Care Respiratory Journal. UK; 2010.
Sabina Antonela Antoniu. New Therapeutic Options in the
Management of COPD – focus on roflumilast. UK; 2011.
THANK YOU