MD Conference Express ATS 2013 - (Page 18)
CLINICAL TRIAL HIGHLIGHTS
Adverse events such as headache, diarrhea, nausea,
dizziness, and jaw pain occurred significantly more
frequently in the combination arm, as compared with the
monotherapy arm. Flushing and extremity pain occurred
with similar frequency among both study groups.
Prof. Jing said that, in his opinion, the BEST Study
suggests that adding beraprost to sildenafil therapy in the
treatment of PAH is effective and well tolerated, but should
be further evaluated in additional studies.
Dupilumab Is Safe and Effective for
Controlling Asthma Attacks
Written by Maria Vinall
Dupilumab (SAR231893/REGN668) reduces symptoms
and improves lung function with side effects similar to
placebo in patients with moderate to severe, persistent
asthma. Dupilumab, a fully human monoclonal
interleukin (IL) antibody, is a potent inhibitor of both IL-4
and IL-13. Sally E. Wenzel, MD, University of Pittsburgh,
Pittsburgh, Pennsylvania, USA, presented the results of
a Phase 2, randomized, double-blind study comparing
the effect of dupilumab and placebo on the incidence
of asthma exacerbations in patients with persistent
moderate-to-severe eosinophilic asthma [NCT01312961].
Patients (n=52 in each group) with persistent
(≥12 months) asthma defined as airway inflammation likely
to be eosinophilic (≥300 cells/µL or sputum eosinophils
≥3%), with asthma partially controlled or uncontrolled on
inhaled corticosteroid (ICS) plus long-acting b-agonist
(LABA) therapy and on a stable dose of either fluticasone/
salmeterol, budesonide/formoterol, or mometasone/
formoterol combination therapy for ≥1 month prior to screening
were enrolled in the study. The study consisted of a maximum
2-week screening period, followed by 12 weeks of treatment (or
until asthma exacerbation), and 8 weeks of follow-up.
Patients were switched to fluticasone/salmeterol
for 4 weeks at randomization, after which LABA was
withdrawn. The primary outcome was the number of
patients experiencing an asthma exacerbation after 12
weeks. Exacerbation was defined as ≥30% reduction
from baseline in morning expiratory flow rate (PEF) on 2
consecutive days, ≥6 additional reliever inhalations per 24
hours on 2 consecutive days, or exacerbation of asthma
requiring systemic glucocorticoid treatment, an increase
in inhaled glucocorticoids of at least 4 times the most
recent dose, or hospitalization for asthma, as determined
by the investigator.
There were seven secondary outcomes including
changes in forced expiratory volume in 1 second (FEV1),
morning/ evening PEF, reliever use, 5-item Asthma Control
Questionnaire (ACQ5), asthma symptom scores, nocturnal
18
July 2013
awakenings, and the Sino-Nasal Outcome Test (SNOT-22).
Tolerability measures included the proportions of patients
with treatment-emergent adverse events (TEAEs), serious
adverse events (SAEs) and discontinuations due to TEAEs.
Dupilumab (300 mg) was administered subcutaneously
QW for 12 weeks.
The percentage of predicted baseline FEV1 values (~72%),
ACQ scores (2.08), mean number of asthma exacerbations
in the past 2 years (1.38), and percentage of prior ICS/
LABA combination therapy doses were similar between the
groups. At the end of treatment, 3 (6%) patients treated with
dupilumab had an asthma exacerbation compared with
23 (44%) on placebo, corresponding to an 87% relative risk
reduction (OR 0.08; 95% CI, 0.02 to 0.28; p<0.0001).
Time to asthma exacerbation was longer and risk of
exacerbation reduced with dupilumab (Table 1). The
cumulative exacerbation rate increased over the 12-week
study period in the placebo group while remaining little
changed in the dupilumab group. All secondary endpoint
measures favored dupilumab (Table 1).
Table 1. Secondary Endpoints
Outcome
Difference, Dupilumab
vs Placebo (95% CI)
p Value
KM estimate for asthma exacerbation
probability at 12 weeks
0.10 (0.03 to 0.34)
<0.001
Change in FEV1
0.27 (.011 to 0.42)
<0.001
Change in AM PEF
34.6 (10.6 to 58.5)
0.005
Change in PM PEF
22.7 (–0.7 to 46.0)
0.06
Change in ACQS
–0.73 (–1.15 to -0.30)
Change in AM symptom score
–0.7 (–0.9 to –0.4)
<0.001
0.001
Change in PM symptom score
–0.7 (–0.9 to –0.4)
<0.001
Change in number of
nocturnal awakenings
–0.2 (–0.5 to 0.0)
0.05
Change in SNOT-22
–8.49 (–13.96 to –3.03)
Change in number of reliever
inhalations
–0.2 (–2.9 to –1.2)
0.003
<0.001
TEAEs were observed in a similar proportion of patients
in each group (81% of the dupilumab- and 77% of placebotreated patients ). The AEs were generally nonspecific and
of mild-to-moderate intensity. Injection site reactions,
nasopharyngitis, nausea and headache occurred more
often in the dupilumab group. Upper respiratory tract
infections were more common among placebo-treated
patients. There were 4 SAEs (3 in the placebo group and 1 in
the dupilumab group); none were considered to be related
to the study drug. There were no deaths.
Dupilumab appears to be effective and safe for
preventing and controlling protocol defined asthma
exacerbations and improving lung function and asthma
control both after addition to ICS/LABA and following
ICS/LABA withdrawal in patients with moderate to severe,
persistent asthma with elevated eosinophil levels.
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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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