2 DR Reza Maximizing Dual Bronchodilators For COPD Patient's Benefit DR Reza Kurniawan T, SPP FCCP
2 DR Reza Maximizing Dual Bronchodilators For COPD Patient's Benefit DR Reza Kurniawan T, SPP FCCP
2 DR Reza Maximizing Dual Bronchodilators For COPD Patient's Benefit DR Reza Kurniawan T, SPP FCCP
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
Cardiovascular disease
4.5 million
Cancers
17.2 million
7.5 million Chronic respiratory disease
Diabetes
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
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
• Reduce breathlessness
• Improve day and night symptoms
• Reduce the need for rescue medication
• Improve quality of life
• Reduce exacerbations
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
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
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
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)
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
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
(Supportive analysis)
IND/GLY N=1651; SFC N=1656 p<0.001
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.
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
• Reduce breathlessness
• Reduce the need for rescue medication
• Improve quality of life
• Reduce exacerbations
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
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