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Review
. 2021 Aug 27;9(9):1096.
doi: 10.3390/biomedicines9091096.

The Role of Dupilumab in Severe Asthma

Fabio Luigi Massimo Ricciardolo  1 , Francesca Bertolini  1 , Vitina Carriero  1
Affiliations
Review

The Role of Dupilumab in Severe Asthma

Fabio Luigi Massimo Ricciardolo et al. Biomedicines. .

Abstract

Dupilumab is a fully humanized monoclonal antibody, capable of inhibiting intracellular signaling of both interleukin (IL)-4 and IL-13. These are two molecules that, together with other proinflammatory cytokines such as IL-5 and eotaxins, play a pivotal role in orchestrating the airway inflammatory response defined as Type 2 (T2) inflammation, driven by Th2 or Type 2 innate lymphoid cells, which is the major feature of the T2 high asthma phenotype. The dual inhibition of IL-4 and IL-13 activities is due to the blockade of type II IL-4 receptor through the binding of dupilumab with the subunit IL-4Rα. This results in the repression of STAT6 and in the suppression of subsequent de novo formation of several molecules involved in the T2 inflammatory signature. Several clinical trials tested the efficacy and safety of dupilumab in large populations of uncontrolled severe asthmatics, revealing significant improvements in lung function, asthma control, and exacerbation rate. Similar results were reported when dupilumab was employed in patients harboring pathogenetic processes related to T2 immune response, such as atopic dermatitis and chronic rhinosinusitis. In this review, we provide an overview of the recent research in the field of respiratory medicine about dupilumab mechanism of action and its effects.

Keywords: IL-13; IL-4; dupilumab; phenotype; severe asthma.

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Conflict of interest statement

Fabio L.M. Ricciardolo reports grants, personal fees, and other compensation from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Guidotti, Lusofarmaco, Menarini, Mundipharma and Novartis, personal fees and grants to support scientific research from Sanofi, all outside of the submitted work. Vitina Carriero received a grant form Sanofi. Francesca Bertolini declares no conflict of interest.

Figures

Figure 1
Figure 1
The role of Th2 and ILC2 in asthma. After injury, epithelial cells release allarmins (IL-25, IL-33, and TSLP) that activate ILC2 cells and dendritic cells (DC). Upon allergen/antigen uptake, processing, and presentation to naïve T cells, DC promote the differentiation of naïve T helper cells into Th2 lymphocytes. ILC2 and Th2 secrete pro-inflammatory cytokines, exerting key roles in T2 immune response. Created with BioRender.com (accessed on 23 July 2021).
Figure 2
Figure 2
Dupilumab exerts dual blockade of IL-4/IL-13 signaling by binding IL-4Rα. Through this mechanism of action, dupilumab can induce beneficial effects in patients with T2 pathologies. AD: atopic dermatitis, CRS: chronic rhinosinusitis, EASI: Eczema Area and Severity Index, FEV1: Forced expiratory volume in the first second, ↓: reduction, ↑: improvement.
See this image and copyright information in PMC

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