Dataset Information

Dupilumab reduced impact of severe exacerbations on lung function in patients with moderate-to-severe type 2 asthma.

ABSTRACT:

Background

Severe asthma exacerbations increase the risk of accelerated lung function decline. This analysis examined the effect of dupilumab on forced expiratory volume in 1 s (FEV₁ ) in patients with moderate-to-severe asthma and elevated type 2 biomarkers from phase 3 LIBERTY ASTHMA QUEST (NCT02414854).

Methods

Changes from baseline in pre- and post-bronchodilator (BD) FEV₁ and 5-item Asthma Control Questionnaire (ACQ-5) scores were assessed in patients with elevated type 2 biomarkers at baseline (type 2-150/25: eosinophils ≥150 cells/μl and/or fractional exhaled nitric oxide [FeNO] ≥25 ppb; type 2-300/25: eosinophils ≥300 cells/μl and/or FeNO ≥25 ppb), stratified as exacerbators (≥1 severe exacerbation during the study) or non-exacerbators.

Results

In exacerbators and non-exacerbators, dupilumab increased pre-BD FEV₁ by Week 2 vs placebo; differences were maintained to Week 52 (type 2-150/25: LS mean difference (LSMD) vs placebo: 0.17 L (95% CI: 0.10-0.24) and 0.17 L (0.12-0.23); type 2-300/25: 0.22 L (0.13-0.30) and 0.21 L (0.15-0.28)), in exacerbators and non-exacerbators, respectively (p < .0001). Similar trends were seen for post-BD FEV₁ . Dupilumab vs placebo also showed significantly greater improvements in post-BD FEV₁ 0-42 days after first severe exacerbation in type 2-150/25 (LSMD vs placebo: 0.13 L [0.06-0.20]; p = .006) and type 2-300/25 (0.14 L [0.06-0.22]; p = .001) patients. ACQ-5 improvements were greater with dupilumab vs placebo in both groups.

Conclusion

Dupilumab treatment led to improvements in lung function independent of exacerbations and appeared to reduce the impact of exacerbations on lung function in patients who experienced a severe exacerbation during the study.

SUBMITTER: Papi A

PROVIDER: S-EPMC10087924 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Dupilumab reduced impact of severe exacerbations on lung function in patients with moderate-to-severe type 2 asthma.

Papi Alberto A Corren Jonathan J Castro Mario M Domingo Christian C Rogers Linda L Chapman Kenneth R KR Jackson Daniel J DJ Daizadeh Nadia N Pandit-Abid Nami N Gall Rebecca R Jacob-Nara Juby A JA Rowe Paul J PJ Deniz Yamo Y Ortiz Benjamin B

Allergy 20220809 1

<h4>Background</h4>Severe asthma exacerbations increase the risk of accelerated lung function decline. This analysis examined the effect of dupilumab on forced expiratory volume in 1 s (FEV<sub>1</sub> ) in patients with moderate-to-severe asthma and elevated type 2 biomarkers from phase 3 LIBERTY ASTHMA QUEST (NCT02414854).<h4>Methods</h4>Changes from baseline in pre- and post-bronchodilator (BD) FEV<sub>1</sub> and 5-item Asthma Control Questionnaire (ACQ-5) scores were assessed in patients wi ...[more]

PMID: 35899469

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Project description:Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation. In the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) in patients with uncontrolled, moderate-to-severe asthma, add-on dupilumab 200 mg or 300 mg every 2 weeks reduced exacerbations and improved forced expiratory volume in 1 s (FEV1) and quality of life over 52 weeks. This analysis evaluates dupilimab's effect on lung function in the overall population, and subgroups with baseline elevated type 2 inflammatory biomarkers. Patients were randomised to 52 weeks of subcutaneous dupilumab 200 mg every 2 weeks, 300 mg every 2 weeks, or matched-volume placebos. Lung function outcomes were analysed in the overall population, in patients with ≥150 eosinophils·µL-1, ≥300 eosinophils·µL-1, ≥25 ppb fractional exhaled nitric oxide (FeNO), and both ≥150 eosinophils·µL-1 and ≥25 ppb FeNO, at baseline. Dupilumab treatment (200 mg and 300 mg every 2 weeks) resulted in significant improvements versus placebo after 52 weeks in pre-bronchodilator FEV1 (0.20 and 0.13 L, respectively, versus placebo) and post-bronchodilator FEV1 (0.19 and 0.13 L, respectively), forced vital capacity (FVC) (0.20 and 0.14 L, respectively), forced expiratory flow (0.19 and 0.13 L·s-1, respectively) and pre-bronchodilator FEV1/FVC ratio (1.75% and 1.61%, respectively) in the overall population (p<0.001). Difference versus placebo in post-bronchodilator FEV1 slope of change (weeks 4-52) was significant (0.04 L·year-1; p<0.05). Greater improvements were achieved in patients with elevated baseline blood eosinophil and/or FeNO levels for most outcomes. Dupilumab improves lung function outcomes, including large and small airway measurements and fixed airway obstruction, in patients with uncontrolled, moderate-to-severe asthma; particularly in patients with elevated biomarkers of type 2 inflammation.

Project description:BackgroundAsthma affects millions of patients across the globe and also accounts for numerous mortalities every year. The current pharmacologic approach to the treatment of asthma includes the use of glucocorticoids and beta-agonists mainly. However, these conventional therapies have poor controllability of moderate-to-severe asthma and also produce several side effects on their long-term use. These limitations had led to the development of biologics targeting the mediators involved in T helper 2-inflammation associated with the pathogenesis of asthma such as interleukin (IL) 4, IL-5, and IL-13. dupilumab, a fully human monoclonal antibody, an IL-4 receptor alpha-antagonist targeting IL-13 and IL-4 has a potential role in treatment of moderate-to-severe asthma and was approved by the Food and Drug Administration on October 19, 2018. The dual-antagonistic action of dupilumab on IL-4 and IL-13 receptors renders it more efficient in asthma treatment.ObjectivesTo review the efficacy and safety profile of dupilumab in the treatment of moderate-to-severe asthma.MethodsSystematic search was performed via PubMed, Cochrane library, Embase, and ClinicalTrials.gov using the key words dupilumab, moderate-to-severe asthma, interleukin, IL-13, IL-4, and monoclonal antibody. Randomized controlled trials that compared between placebo and dupilumab in patients with uncontrolled asthma were included and observational studies were excluded in this review.ResultsThe review of selected literature reveals that addition of dupilumab to conventional therapy improves forced expiratory volume in 1 second and reduces the risk of severe asthma exacerbations in patients. No significant differences in incidence of adverse drug reactions/adverse drug events were observed between dupilumab and placebo groups except higher rates of injection site reactions in the dupilumab group.ConclusionsConcomitant use of dupilumab with long-acting beta agonists used in combination with inhaled corticosteroids, improves clinical outcomes and quality of life in patients with moderate to severe asthma. Although dupilumab has a promising role in treatment of patients with asthma, it is still in the emerging stage for its acceptance globally. Ongoing studies will help to determine dupilumab's long-term efficacy and safety for its future extensive use.

Dataset Information

Dupilumab reduced impact of severe exacerbations on lung function in patients with moderate-to-severe type 2 asthma.

Background

Methods

Results

Conclusion

Publications

Dupilumab reduced impact of severe exacerbations on lung function in patients with moderate-to-severe type 2 asthma.

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