Dataset Information

Dupilumab in the management of moderate-to-severe asthma: the data so far.

ABSTRACT: Severe asthma constitutes illness in a relatively small proportion of all patients with asthma, but it is a major public health problem - with considerable effect on morbidity, mortality, as well as a high burden on health care resources. Regardless of effective treatments being widely available and the existence of treatment guidelines, a large population of severe asthma cases remain uncontrolled. Achieving and maintaining asthma control in this group of patients is, therefore, of utmost importance. The recognition of distinct inflammatory phenotypes within this population has driven the development of targeted biological therapies - particularly, selective targeted monoclonal antibodies (mAbs). It is noteworthy that in approximately 50% of these patients, there is strong evidence of the pathogenic role of T helper type-2 (Th2) cytokines, such as interleukin (IL)-4 and IL-13, orchestrating the eosinophilic and allergic inflammatory processes. Among the recently developed antiasthma biologic drugs, the mAb dupilumab is very promising given its ability to inhibit the biological effects of both IL-4 and IL-13. In this review, we focused on IL-4 and IL-13, as these interleukins are considered to play a key role in the pathophysiology of asthma, and on dupilumab, an anti-IL-4 receptor human mAb, as a forthcoming treatment for uncontrolled severe asthma in the near future.

SUBMITTER: Barranco P

PROVIDER: S-EPMC5589101 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Dupilumab in the management of moderate-to-severe asthma: the data so far.

Barranco Pilar P Phillips-Angles Elsa E Dominguez-Ortega Javier J Quirce Santiago S

Therapeutics and clinical risk management 20170901

Severe asthma constitutes illness in a relatively small proportion of all patients with asthma, but it is a major public health problem - with considerable effect on morbidity, mortality, as well as a high burden on health care resources. Regardless of effective treatments being widely available and the existence of treatment guidelines, a large population of severe asthma cases remain uncontrolled. Achieving and maintaining asthma control in this group of patients is, therefore, of utmost impor ...[more]

PMID: 28979129

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Project description:Background: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. Methods: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 (F eNO), and both ?150?eosinophils·µL-1 and ?25?ppb F eNO, at baseline. Results: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 F eNO levels for most outcomes. Conclusions: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:Background:Asthma 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. Objectives:To review the efficacy and safety profile of dupilumab in the treatment of moderate-to-severe asthma. Methods:Systematic 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. Results:The 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. Conclusions:Concomitant 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 in the management of moderate-to-severe asthma: the data so far.

Publications

Dupilumab in the management of moderate-to-severe asthma: the data so far.

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