CURRICULUM VITAE

Nama : Reza Kurniawan Tanuwihardja

Tempat / tgl. Lahir : Jakarta / 20 Januari 1978
Alamat : Jl. Gandapura no.12, Bandung 40113
Telepon : (022) 7231263
Handphone : 085883723592
Email : reza.tanuwihardja@yahoo.com ,
reza.tanuwihardja@gmail.com

RIWAYAT PENDIDIKAN

1996 - 2002 Pendidikan dokter umum, Fakultas Kedokteran Universitas Udayana, Bali

2004 - 2006 Internal Medicine Residency training, Department of Internal Medicine, San Juan de
Dios Hospital, Manila, Philippines
2007 - 2009 Pulmonary Medicine Fellowship training, Institute of Pulmonary Medicine, St. Luke's
Medical center, Manila, Philippines
2010 - 2011 Program adaptasi spesialis paru, Departemen Pulmonologi dan Ilmu Kedokteran
Respirasi, Fakultas Kedokteran Universitas Indonesia / RS Persahabatan, Jakarta
 Maximizing
Dual Bronchodilators
For COPD Patient’s Benefit

dr. Reza Kurniawan T, SpP., FCCP

 COPD Definition

“Chronic Obstructive Pulmonary Disease (COPD) is a

common, preventable and treatable disease that is
characterized by persistent respiratory symptoms and
airflow limitation that is due to airway and/or alveolar
abnormalities usually caused by significant exposure to
noxious particles or gases.”
Chronic respiratory diseases account for a large
proportion of global mortality

• In 2008, of the 57 million deaths that occurred globally 63% (35.9

million) were due to non-communicable diseases, comprising
mainly:1,2
1.3 million

Cardiovascular disease
4.5 million

Cancers
17.2 million
7.5 million Chronic respiratory disease

Diabetes

• COPD prevalence estimates vary by country owing to differences

in survey methods, diagnostic criteria and analytical approaches
(e.g. self-reporting of COPD diagnosis)3
1. World Health Organization. Global Action Plan for the Prevention and Control of NCDs 2013–2020; 2. World Health Organization. Deaths from NCDs 2014; 3. Halbert
RJ, et al. Eur Respir J 2006
 Estimated COPD prevalence varies across
Asia–Pacific countries
10
Projected prevalence of COPD (%)

8
6.5 6.7
6.1 6.3
5.9
6 5.6 5.4
5.0
4.7 4.7

4 3.5 3.5

Model projections of the prevalence of moderate-to-severe COPD in individuals ≥30 years for 12
countries in the Asia–Pacific region, based on a systematic review of published literature for the
identification and quantification of major COPD risk factors

Regional COPD Working Group. Respirology 2003

 Inactivity in patients with COPD leads to
deconditioning, anxiety and depression, and a
reduction in HRQoL

HRQoL = health-related quality of life

Adapted from Cooper CB. Respir Med 2009 ZuWallack R. COPD 2007
 COPD will be the third biggest
global killer by 2030

World Health Organization. World Health Statistics 2008

 Burden of COPD may be greater than
estimated owing to underdiagnosis

Diagnosed

Undiagnosed,
but symptomatic

The National Outcomes Strategy for COPD, UK Department of Health 2011; Jones RC et al. Lancet Respir Med 2014
 Diagnosis of COPD must be
confirmed by spirometry

1. GOLD 2017; 2. Freeman D, Price D. BMJ 2006

Pharmacologic
interventions:
Bronchodilators
 Bronchodilators:
the cornerstone of COPD treatment

• Improve FEV1 and reduce bronchoconstriction

• Inhibit dynamic hyperinflation and improve exercise capacity

• Reduce breathlessness
• Improve day and night symptoms
• Reduce the need for rescue medication
• Improve quality of life

• Reduce exacerbations

FEV1 = forced expiratory volume in 1 second

GOLD 2017
 LABAs and LAMAs improve lung function, reduce
breathlessness, improve quality of life, reduce
exacerbations
1. LABAs (e.g. indacaterol and salmeterol) and LAMAs (e.g. glycopyrronium
and tiotropium) significantly reduce airflow limitation in COPD, as measured
by trough FEV11,2
2. LABAs (e.g. indacaterol and salmeterol) and LAMAs (e.g. glycopyrronium
and tiotropium) significantly reduce breathlessness in COPD, as measured by
TDI3,4
3. LABAs (e.g. indacaterol) and LAMAs (e.g. glycopyrronium and tiotropium)
significantly improve HRQoL n COPD, as measured by SGRQ5,6
4. LABAs (e.g. indacaterol) and LAMAs (e.g. glycopyrronium) significantly
reduce the rate of exacerbations in COPD7,8

HRQoL = health-related quality of life

1. Kornmann O, et al. Eur Respir J 2011; 2. Adapted from Kerwin E, et al. Eur Respir J 2012; 3. Kornmann O, et al. Eur Respir J 2011; 4. Adapted from Kerwin E, et al. Eur Respir J 2012; 5.
Donohue JF, et al. Am J Respir Crit Care Med 2010; 6. Kerwin E, et al. Eur Respir J 2012; 7. Chapman KR, et al. Chest 2011; 8. Kerwin E, et al. Eur Respir J 2012
 Combining bronchodilators in COPD

In accordance with GOLD, there is considerable evidence and

guidance to support use of the combination of a LAMA and a
LABA in COPD1,2

• Long-acting bronchodilator combinations significantly increase lung

function and reduce patient symptoms compared with bronchodilator
monotherapy,1,3 and reduce exacerbations compared with
bronchodilator monotherapy and ICS/LABA4,5
• A number of free and fixed-dose LAMA and LABA combinations have
been studied and results indicate significant benefit for this approach2–6

GOLD = Global initiative for chronic Obstructive Lung Disease LABA = long-acting β2-agonist
LAMA = long-acting muscarinic antagonist

1. GOLD 2017; 2. Tashkin DP, et al. Respir Res 2013; 3. Tashkin DP, et al. COPD 2009; 4. Wedzicha J, et al. NEJM. 2016; 5. Wedzicha J, et al. Lancet Respir
Med 2013; 6. Bateman ED, et al. Expert Rev Respir Med 2014
 LABA plus LAMA combinations provide greater
improvements in lung function versus individual
components
SHINE1: W eek 26 NCT013136502 Day 169
∆=200 mL p<0.001

∆=80 mL p<0.001 All p<0.001 vs placebo

∆=90 mL p<0.001 ∆=95 mL, p≤0.001

1.5 ∆=70 mL p<0.001 0.20 ∆=52 mL, p≤0.01

Trough FEV1 (L) difference vs placebo

1.45 0.167

0.15
1.4 1.37 1.38
Trough FEV1 (L)

1.36 0.115

0.10
0.072
1.3
1.25
0.05

1.2
0 0.00
Placebo Open- Glycopyrro- Indacaterol QVA149
Umeclidinium 62.5 Umeclidinium 62.5 Vilanterol 25 μg q.d.
(n=232) label nium 150 μg q.d. 110/50 μg
tiotropium 50 μg q.d. (n=476) q.d. μg/Vilanterol 25 μg μg q.d. (n=418) (n=421)
18 μg q.d. (n=473) (n=474) q.d. (n=413)
(n=480)

FEV1 = forced expiratory volume in 1 second

LABA = long-acting β2-agonist; LAMA = long-acting muscarinic antagonist; q.d. = once daily
1. Bateman ED, et al. Eur Respir J 2013; 2. Donohue JF, et al. Respir Med 2013
 LABA plus LAMA provides greater improvements in
breathlessness versus placebo
Week 26 Day 168
p<0.01

p<0.05

p<0.05
Patients with ≥1-point improvement in TDI total score

p≤0.001
70 p=ns 68.1% 70%
70 p≤0.05
63.7% 64.6%
59.2% 60% p≤0.01 58%
60 57.5% 60
53%
51%
50 50%
50

TDI Responder (%)

41%
40 40%
40

30 30%
30

20 20%
20

10 10%
10

0 0%0
Placebo Open-label Glycopyrronium Indacaterol QVA149 Placebo
(n=232) tiotropium 50 μg q.d. 150 μg 110/50 μg
Placebo Umeclidinium Umeclidinium Vilanterol 25 μg
18 μg q.d. (n=473) q.d. q.d. (n=280) 62.5 μg/Vilanterol 62.5 μg q.d. q.d. (n=421)
(n=480) (n=476) (n=474) 25 μg q.d. (n=418)
(n=413)

LABA = long-acting β2-agonist; LAMA = long-acting muscarinic antagonist; ns = not statistically significant q.d. = once daily; TDI = transitional dyspnea index

1. Bateman ED, et al. Eur Respir J 2013; Donohue JF, et al. Respir Med 2013
 SPARK: LABA plus LAMA reduced the risk of
exacerbations vs LAMA
• 64-week treatment, multicenter, randomized, double-blind, parallel-group study in patients with
severe-to-very severe airflow limitation* and ≥1 COPD exacerbation requiring treatment with
antibiotics, systemic corticosteroids or both in the past year

*FEV1 <50% predicted; †mild/moderate/severe

Open-label tiotropium 18 μg q.d. (n=737)
GLY = glycopyrronium; IND = indacaterol
LAMA = long-acting muscarinic antagonist
Wedzicha JA, et al. Lancet Respir Med 2013
 FLAME: LABA plus LAMA demonstrated superiority
versus LABA/ICS for rate of all exacerbations
• 52-week, multicenter, randomized, double-blind, double-dummy, non-inferiority study in
patients with moderate-to-very severe airflow limitation*, mMRC grade ≥2 and a documented
history of ≥1 COPD exacerbation in the past year
Rate ratio (95% Cl)
Superiority Non-inferiority
margin margin

Per-protocol set 0.83 0.89 0.96

(Primary analysis)
IND/GLY N=1518; SFC N=1544 p=0.003

Full analysis set 0.82 0.88 0.94

(Supportive analysis)
IND/GLY N=1651; SFC N=1656 p<0.001

0.8 0.9 1.0 1.15

Favors IND/GLY Favors SFC
110/50 μg q.d. 50/500 μg b.i.d.
*FEV1 of at least 25% to <60% predicted; †mild/moderate/severe
GLY = glycopyrronium; ICS = inhaled corticosteroid; IND = indacaterol LABA = long-acting β2-agonist; mMRC = modified Medical Research Criteria SFC = salmeterol fluticasone

Wedzicha JA, et al. N Engl J Med 2016

FLAME: Dual bronchodilation significantly delayed
time to first exacerbation versus LABA/ICS

Analysis of the FAS. GLY = glycopyrronium; HR = hazard ratio; ICS = inhaled corticosteroid; IND = indacaterol; LABA = long-acting β2-agonist; mMRC = modified Medical
Research Criteria; SFC = salmeterol fluticasone
Wedzicha JA, et al. N Engl J Med 2016
Fixed-dose LABA/LAMA combinations: convenience
and compliance
Fixed-dose combinations (FDCs) offer the potential of improved
convenience and compliance over use of separate inhalers1–2
Patients with COPD who use a single inhaler versus multiple inhalers consistently
show a longer time to first exacerbation2
Single inhaler users also have fewer exacerbations, a lower risk of exacerbation,
and lower healthcare resource use and costs2
–
Multiple-inhaler users Single-inhaler users
50
Patients experiencing first

46.4%
40
exacerbation (%)

30 28.2% 36.5%
16.8%
20
21.5%
8.2%
10 12.6%
5.5%
0
0 90 180 270 360
Number of days until first exacerbation
LABA = long-acting β2-agonist
LAMA = long-acting muscarinic antagonist

1. Tashkin DP, et al. Respir Res 2013; 2. Yu AP, et al. Respir Med 2011
 Patients using the Breezhaler® made fewer critical
handling errors than patients using other inhalation
devices
1. GPs (n=212) and pulmonologists (n=50) assessed COPD patients (n=2935)
handling of 3,993 devices
– Patients used their own medication/device
– Patients used their usual inhalation technique, with no instruction
– Physicians paid particular attention to dose preparation and delivery
46.9
50 43.8 (43.0–50.8)
involved ≥1 critical handling error*

(39.1–48.6)
% device handing episodes that

40
32.1
(27.7–36.6) 30.0
29.3
(25.6–32.9) (28.5–31.6)
30
21.2
(17.5–25.0)
20 15.4
(13.0–17.8)

10

0
Breezhaler® Diskus® Handihaler® pMDI Respimat® Turbohaler® Total#
(n=876) (n=452) (n=598) (n=422) (n=625) (n=420) (n=3,393)

Data presented as % (95% CI). *Errors were considered critical if they could have substantially affected dose delivery to the lungs; #total number of evaluated devicesCI = confidence interval; n =
number of devices; pMDI = pressurised metered-dose inhaler
Molimard M, et al. Eur Respir J 2016
 Patients prescribed devices requiring similar
inhalation techniques did better than those
prescribed devices requiring different techniques
• Patients prescribed devices with similar inhalation techniques had a significantly lower rate of
moderate/severe exacerbations and were less likely to require a higher dose of rescue
medication versus patients using devices requiring them to mix techniques
Adjusted* IRR/proportional OR for similar devices cohort, with 95% CI

*IRR adjusted by antibiotic course, asthma diagnosis and paracetamol use. OR adjusted by baseline SABA and osteoporosis. CI = conf idence interval; IRR = incidence rate ratio; OR = odds
ratio; SABA = short-acting β2-agonist.

Bosnic-Anticevich S, et al. Int J COPD 2017

Critical errors in inhaler technique were associated
with moderate-to-severe and severe exacerbations
• The rate moderate-to-severe and severe exacerbations in the previous 3 months
was significantly higher in patients with at least one critical error vs no error in
device technique (both p<0.01)
45 No error (n=857)
38.5* Non-critical error (n=1,236)
40
% patients experiencing exacerbations

35.6 (35.4–41.5) Critical error (n=1,019)

32.1 (32.9–38.4)
35
(28.9–35.4)
in the previous 3 monthsa

30

25

20

15

10 6.9*
4.6 (5.3–8.5)
3.3 (3.4–5.8)
5 (2.0–4.5)

0
Moderate-to-severe# exacerbation Severe¶ exacerbation
Data presented as % (95% CI). aRestricted to patients treated for at least 3 months with the device (no error n=794; non-critical error n=1,153; critical error n=975); *p<0.01 for critical errors
vs no error; #antibiotics, systemic corticosteroids, emergency room visit or hospitalization; ¶emergency room visits or hospitalization. CI = confidence interval; n = total number of errors

Molimard M, et al. Eur Respir J 2016

 Efficacy of fixed-dose LABA/LAMA combinations
• A number of FDCs are now available or are currently in
development1
– In all cases, there is evidence of significantly improved clinical outcomes with
the combinations versus monotherapy2,3

• Improve FEV1 and reduce bronchoconstriction

• Reduce breathlessness
• Reduce the need for rescue medication
• Improve quality of life

• Reduce exacerbations

FDC = fixed-dose combination;

FEV1 = forced expiratory volume in 1 second;
LABA = long-acting β2-agonist
LAMA = long-acting muscarinic antagonist

1. GOLD 2017; 2. Tashkin DP, et al. Respir Res 2013; 3. Bateman ED, et al. Expert Rev Respir Med 2014
 Safety of combining LABAs and LAMAs1–7

• LABAs and LAMAs have been found to be generally well

tolerated in clinical trials in patients with COPD
• Good safety profiles have been established with
LABA/LAMA fixed-dose combinations in studies of up to 64
weeks duration
• Free combinations of LAMA/LABA also seem well tolerated

LABA = long-acting β2-agonist

LAMA = long-acting muscarinic antagonist

1. Tashkin DP, et al. Respir Res 2013; 2. Wedzicha JA, et al. Respir Med 2014; 3. Welte T, et al. Eur Respir J 2013; 4. Wedzicha JA, et al. Lancet Respir Med 2013; 5. Wedzicha
JA, et al. N Engl J Med 2016; 6. Oba Y, et al. Thorax 2016; 7. Vincken W, et al. Int J Chron Obstruct Pulmon Dis 2014
Thank You