MD Conference Express ATS 2013 - (Page 19)
Written by Wayne Kuznar
A once-daily inhaled dual bronchodilator consisting of
a long-acting b2-agonist and a long-acting muscarinic
antagonist (QVA149) significantly improved self-reported
shortness of breath and lung function compared with
placebo and tiotropium in patients with moderate to
severe chronic obstructive pulmonary disease (COPD).
Donald A. Mahler, MD, Dartmouth-Hitchcock Medical
Center, Lebanon, New Hampshire, USA, presented results
of the Effect of QVA149 on Dyspnea in Patients With
Chronic Obstructive Pulmonary Disease study [BLAZE;
NCT01490125], a multicenter, randomized, blinded, doubledummy, placebo-controlled, 3-period, crossover trial.
Dyspnea in COPD is not always controlled adequately
by bronchodilator monotherapy, providing the rationale for
combining two bronchodilators with different mechanisms
of action [Rabe KF et al. Am J Respir Crit Care Med 2007;
Vestbo J et al. Am J Respir Crit Care Med 2013]. QVA149 is
an investigational fixed-dose combination of indacaterol
maleate 110 µg and glycopyrronium bromide 50 µg.
QVA149 had previously demonstrated improvements in
dyspnea versus its individual components, tiotropium,
and salmeterol/fluticasone using the interviewer-based
Transition Dyspnea Index (TDI) [Bateman ED et al. Eur
Respir J 2013; Vogelmeier C et al. Respir Med 2013].
In BLAZE, patients with moderate to severe COPD
(n=246) were randomized to once-daily QVA149, tiotropium
18 µg, or placebo. Patients were current or former smokers,
had a Modified Medical Research Council scale of >2 at
screening, a postbronchodilator forced expiratory volume
in 1 second (FEV1) ≥30 and <80% predicted, and FEV1/
forced vital capacity <0.7. There was a 2-week washout
between crossover periods.
The primary objective was superiority of QVA149 versus
placebo on the improvement in patient-reported levels
of breathlessness during daily activities using the SelfAdministered Computerized (SAC) version of the Baseline
Dyspnea Index (BDI)/TDI after 6 weeks. The SAC version of
the BDI/TDI was developed as a tool to provide direct patientreported ratings of dyspnea and to provide a standard method
to reduce the potential bias with an interviewer [Mahler DA
et al. COPD 2004]. The secondary objective was superiority of
QVA149 versus tiotropium on the same endpoint.
Other secondary objectives included evaluation for lung
function by FEV1 area under the curve from 0 to 4 hours
(AUC0−4h) and rescue medication use over 6 weeks.
Figure 1. Subgroup Analysis by COPD Severity
Placebo
QVA149
Tiotropium
∆=1.16; p=0.002
∆=0.76; p=0.042
∆=1.92; p<0.001
2.0
1.48
∆=0.75; p<0.004
∆=0.36; p=ns
1.5
∆=1.11; p<0.001
Total TDI Score
Once-Daily QVA149 Improves
Breathlessness in COPD Patients
After 6 weeks of treatment, QVA149 significantly
improved patient self-reported shortness of breath during
daily activities versus placebo (∆=1.37; p<0.001) and
versus tiotropium (∆=0.49; p=0.021). Significantly more
moderate COPD patients achieved ≥1 point TDI total
score improvement on QVA149 (35.9%) versus placebo
(18.1%; p<0.001) and tiotropium (24.4%; p=0.012).
Subgroup analysis showed that the improvement in the
SAC TDI with QVA149 was more pronounced in patients
with severe COPD (Figure 1).
0.72
0.62
1.0
0.27
0.5
0
-0.5
-0.48
-1.0
Moderate COPD
-0.44
Severe COPD
COPD=chronic obstructive pulmonary disease; LS=least squares; NS=nonsignificant;
SE=standard error; TDI=Transition Dyspnea Index.
Reproduced with permission from DA Mahler, MD.
QVA149 produced significant and clinically meaningful
improvements in FEV1 AUC0–4h versus placebo and
versus tiotropium on Day 1 and Week 6 (p<0.001 for both
comparisons; Figure 2).
Figure 2. FEV1 Area Under the Curve
Placebo
QVA149
1.7
210 mL*
Tiotropium
230 mL*
140 mL*
70 mL*
330 mL*
110mL*
1.6
FEV 1 AUC 0-4H (L)
This study was published simultaneously with its
presentation at ATS 2013: Wenzel S et al. N Engl J Med 2013.
1.5
1.4
1.3
1.2
0
1.35
1.56
1.5
Day 1
1.3
1.64
1.53
Week 6
AUC 0−4h=area under the curve from 0 to 4 hours; FEV1=forced expiratory volume in 1 second;
LS=least squares; SE=standard error.
Reproduced with permission from DA Mahler, MD.
Official Peer-Reviewed Highlights From the American Thoracic Society International Conference 2013
19
Table of Contents for the Digital Edition of MD Conference Express ATS 2013
MD Conference Express ATS 2013
Contents
Prevention and Early Treatment of Acute Lung Injury
Nocturnal Noninvasive Ventilation Improves Outcomes in Multiple Disorders
Hospital Readmissions: Challenges and Opportunities
EBUS-TBNA: Accurate and Safe for Detecting Sarcoidosis
Data Link Obstructive Sleep Apnea and Type 2 Diabetes
Statin Use Improves Respiratory-Related Mortality in Patients With COPD
Addition of Spironolactone to Ambrisentan May Be a Novel Treatment Strategy to Improve Outcome in Patients With PAH
Haloperidol Does Not Prevent Delirium in Ventilated ICU Patients
Beraprost Plus Sildenafil Effective in Pulmonary Arterial Hypertension
Dupilumab Is Safe and Effective for Controlling Asthma Attacks
Once-Daily QVA149 Improves Breathlessness in COPD Patients
CPAP in CVD and OSA Does Not Significantly Improve Cardiovascular Biomarkers
CPAP Reduces BP in Patients With Resistant Hypertension and Obstructive Sleep Apnea
Effects of Obesity on COPD
Pulmonary Embolism
Ventilator-Associated Pneumonia
Lung Cancer Screening
Idiopathic Pulmonary Fibrosis
Non-Small-Cell Lung Cancer
MD Conference Express ATS 2013
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