An open-label extension study found a consistent safety profile and a maintained efficacy of dupilumab over up to 96 weeks. The LIBERTY ASTHMA TRAVERSE trial included asthma patients with uncontrolled moderate-to-severe asthma who had been enrolled in phase 2 and 3 randomised controlled trials for dupilumab treatment . On the other hand, fevipiprant for therapy of severe asthma did not reach significance in the primary objective of the LUSTER-1 and LUSTER-2 trials .
The LIBERTY ASTHMA TRAVERSE trial included 2,282 patients from 4 parent studies: QUEST (phase 3), DRI (phase 2b), EXPEDITION (phase 2a), and VENTURE (phase 3) . VENTURE assessed the IL-4 receptor alpha antagonist dupilumab for the treatment of asthma patients taking oral corticosteroids (OCS). In the open-label extension study, all patients were treated with add-on 300 mg of dupilumab every second week. Due to an amendment to the study design, 96% of the subject received therapy over 48 weeks and 54% over 96 weeks during the long-term extension. Dr Michael Wechsler (National Jewish Cohen Family Asthma Institute, USA) presented data from DRI, QUEST, and VENTURE for the safety findings and efficacy data for the non-OCS dependent patients from DRI and QUEST.
The primary endpoint of the extension study was the rate of patients with any kind of treatment-emergent adverse events up to week 96. Secondary endpoints included annualised severe exacerbation rate and forced expiratory volume over 1 second (FEV1). “The dupilumab safety profile of the open-label extension was consistent with that in the previously published shorter duration parent studies,” said Dr Michael Wechsler (National Jewish Cohen Family Asthma Institute, USA). A treatment-emergent AE emerged in 76.3% to 87.6% of patients in the different groups; the most common included nasopharyngitis (17.5%-25.9%), bronchitis (9.3%-19%), and injection-site erythema (2.2%-23.4%). Serious treatment-emergent AE occurred in 9.3%-12.6% of participants, and 2.3%-5.6% of treatment-emergent AEs led to permanent discontinuation of dupilumab.
As for exacerbations in the open-label phase, the unadjusted annualised severe exacerbation rate ranged from 0.31-0.35 in non-OCS dependent patients. The corresponding values for dupilumab-treated patients at the end of the parent studies DRI and QUEST were 0.31-0.69 and 0.48-0.56, respectively. In DRI and QUEST, the baseline values for FEV1 were 1.79-1.86 litres and 1.75-1.78 litres, respectively. “By week 96 of the open-label extension, absolute mean FEV1 ranged from 2.02-2.12 litres representing a 13%-22% mean percent change from parent study baseline in the overall population,” stated Dr Wechsler.
He concluded that “long-term treatment with dupilumab was generally well tolerated. Patients exposed to dupilumab for up to 96 weeks, demonstrated maintenance in the clinical efficacy that was observed in the parent studies, including a persistently low exacerbation rate and sustained improvements in lung function.”
Disappointing results of the LUSTER trials
The phase 3 LUSTER-1 and LUSTER-2 studies evaluated patients with severe asthma, including those with high blood eosinophils, treated with GINA step 4 and 5 therapy . Results of the over 1,700 patients randomised within both studies revealed a favourable safety and tolerability profile of the PGD2-receptor antagonist fevipiprant compared with placebo. However, in terms of efficacy, the reduction in exacerbations and improvements in lung function observed were only numerical and did not meet statistical significance.
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- Wechsler M. Dupilumab long-term safety and efficacy in patients with asthma: LIBERTY ASTHMA TRAVERSE. LBA 4613, ERS International Virtual Congress 2020, 7-9 Sept.
- Brightling CE. LUSTER-1 and -2: randomised controlled trials of fevipiprant in severe asthma. LBA 4614, ERS International Virtual Congress 2020, 7-9 Sept.
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Table of Contents: ERS 2020
Letter from the Editor
ERS 2020 Highlights Podcast
COVID-19 and the Lung
COVID-19 infections: Bronchoscopy provides additional diagnostic certainty
COVID-19 vaccines: An ongoing race
COVID-19: What is the risk of reinfection?
COVID-19 App: The Dutch experience
Secondary pulmonary fibrosis: a possible long-term effect of severe COVID-19
COVID-19 survivors benefit from structured follow-up
Early pulmonary rehabilitation post-COVID-19 aids recovery
Asthma – What's New
Mild asthma: A fundamental change in management
Dupilumab shows long-term efficacy in asthma patients
Severe asthma: Oral corticosteroids maintenance therapy associated with toxicity
First-in-class tyrosine kinase inhibitor shows promise in severe asthma
Predicting individual effectiveness of biologics in severe asthma
IL-5 antagonist showed efficacy in chronic rhinosinusitis with nasal polyps
Treatment according to genotype: The future of asthma therapy?
COPD – The Beat Goes On
The role of chronic symptoms as early biomarkers of COPD development
Urgent call for studies in COPD patients aged 40-60 years
Nasal high-flow therapy: a novel treatment option for hypercapnic COPD patients
Exacerbation history is a reliable predictor of future exacerbations
Singing training effective as physical rehabilitation in COPD
Current prediction tools underestimate exacerbation risk of severe COPD patients
Exercise and Sleep: From Impaired Function to New Therapeutic Strategies
CPAP withdrawal has negative consequences for sleep apnoea patients
Physical activity improves AHI in sleep apnoea patients
The Tobacco Epidemic: From Vaping to Cannabis
Poly-use of nicotine products and cannabis: a deadly combination
E-cigarettes: A source of chronic lung inflammation
Social smoking: Do not underestimate the risks
Chronic Cough – State of the Art
LEAD study shows multiple phenotypes in many chronic cough patients
First-in-class P2X3 receptor antagonist shows promise for chronic cough treatment
Lung Cancer Detection
Lung cancer screening: Most patients not eligible 1-2 years prior to diagnosis
Biomarkers: a novel tool to improve lung nodule classification
Distinct changes in lung microbiome precede clinical diagnosis of lung cancer
Best of Posters
Smartphone-based cough detection helpful in predicting asthma deterioration
Reduced lung function associated with cognitive decline in the elderly
Longer hospital stay and fewer transplants for frail ILD patients
Digital asthma intervention improves health and reduces costs
Atezolizumab results show benefit for selected NSCLC patients