Dupilumab: new opportunities for the treatment of asthma and chronic rhinosinusitis with nasal polyps


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Abstract

Airway inflammation plays a crucial role in the development of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The severity of inflammation influences the clinical picture of the disease and, most importantly, the effectiveness of therapy.

To date, the growth in the incidence rate of asthma and CRSwNP is still high and the effectiveness of existing therapy for severe asthma, especially associated with CRSwNP, is unsatisfactory. Therefore, the aim is to investigate novel diagnostic tools and therapies.

The emergence of biologics that target specific inflammatory pathways is a promising step forward to achieve control of severe uncontrolled asthma and recurrent CRSwNP. Dupilumab is one of recently introduced monoclonal antibodies, which has shown significant advances in the treatment of asthma and CRSwNP.

Dupilumab is a fully human monoclonal antibody targeted to interleukin-4 receptor alpha subunit (IL-4Rα) that is a receptor for both IL-4 and IL-13. Thus, it helps to inhibit cytokine T2-signaling (IL-4 and IL-13), since the IL-4/IL-13/STAT6 signaling pathway plays a crucial role in T2-inflammation.

In Russia, dupilumab is currently approved as a treatment for atopic dermatitis (in children over 6 years of age), asthma (in children over 12 years of age) and severe CRSwNP in adults. This article summarizes the main data on dupilumab and its efficacy in patients with asthma and CRSwNP and presents a relevant case report.

About the authors

Miramgul E. Dyneva

National Research Center — Institute of Immunology Federal Medical-Biological Agency of Russia

Author for correspondence.
Email: amanturliva.miramgul@mail.ru
ORCID iD: 0000-0003-1965-8446
SPIN-code: 9504-0251
Scopus Author ID: 57214749322
ResearcherId: D-1943-2019

MD, junior researcher

Russian Federation, 115522, 24 Kashirskoe shosse, Moscow

Gulyumkhan E. Aminova

National Research Center — Institute of Immunology Federal Medical-Biological Agency of Russia

Email: 79263037827@yandex.ru
ORCID iD: 0000-0002-7139-4882
Russian Federation, 115522, 24 Kashirskoe shosse, Moscow

Oksana Kurbacheva

National Research Center — Institute of Immunology Federal Medical-Biological Agency of Russia

Email: kurbacheva@gmail.com
ORCID iD: 0000-0003-3250-0694
SPIN-code: 5698-6436

MD, Dr. Sci. (Med.), Professor

Russian Federation, 115522, 24 Kashirskoe shosse, Moscow

Natalya I. Il'ina

National Research Center — Institute of Immunology Federal Medical-Biological Agency of Russia

Email: instimmun@yandex.ru
ORCID iD: 0000-0002-3556-969X
SPIN-code: 6715-5650

MD, Dr. Sci. (Med.), Professor

Russian Federation, 115522, 24 Kashirskoe shosse, Moscow

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Supplementary files

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2. Fig. 3. Dynamics of CT of the paranasal sinuses: a ― CT picture before treatment (04 March 2019). Signs of CRSwNP. There is the uneven thickening of the mucous membrane of the ethmoid, maxillary, sphenoid sinus; airiness of the sinuses is broken. Soft tissue formation is visualized in left maxillary sinus, probably this is a polyp (blue arrow); b ― CT picture after the start of treatment (28 July 2019). There is a positive trend: airiness is partially restored in the right maxillary, sphenoid sinus, thickening of the mucous membrane is less pronounced in the left maxillary sinus (orange arrows), the size of the polyp also decreased slightly on the left (blue arrow).

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3. Figure 1. IL4 and IL-13 receptor signaling pathways and their key role in the pathogenesis of asthma and CRSwNP Note: IL4 and IL-13 are secreted from several cellular sources and along with other key T2-cytokines such as IL-33, IL-25 and TSLP can stimulate of cells to their secretion. This leads to maintain the inflammatory process in the upper and lower respiratory tract, which explains the severity of asthma and CRSwNP. ILC2 cells, particularly in response to IL-33 secrete large amount IL-13 as well as IL-5. IL-4 has a very high affinity for IL4-Rα with less affinity for γC and IL-13Rα1. IL-4 can signal through either the type 1 or type 2 receptor. IL-13 signals solely via the type 2 receptor. The cell surface density of γC and IL-13Rα1 thus will have significant influence on which receptor combination and which signalling pathway will dominate in cells.

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4. Figure 2. Mechanism of Dupilumab in type 2 inflammation

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