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 Patients were switched to fluticasone/salmeterol for 4 weeks at randomization, after which LABA was withdrawn.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. www.mdconferencexpress.com http://www.mdconferencexpress.com

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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