Dupilumab MOA (mechanism of action of Dupilumab) is discussed here. It inhibits IL-4 and IL-13 signaling pathways and IgE-mediated inflammation.
Dupilumab (generic name) is available by the brand name of Dupixent (Regeneron Pharmaceuticals, Inc). It is used to treat patients with moderate to severe atopic dermatitis with or without concomitant use of topical corticosteroids. It has also been approved by the FDA for the treatment of corticosteroid-dependent uncontrolled asthma in adults and children aged 12 years or more.
Dupilumab is not indicated for the emergency treatment of bronchospasm and acute severe asthma.
Dupilumab MOA (Mechanism of action of Dupixent):
Dupilumab is a monoclonal antibody that is produced by recombinant DNA technology in the Chinese hamster ovary cells.
Class of Immunoglobulin:
Dupilumab is a human monoclonal antibody of the IgG4 class. IgG4 antibodies production is enhanced by cytokines produced by T helper type 2 cells in response to allergic conditions.
Dupilumab (Dupixent) Target receptors:
Dupilumab targets Interleukin 4 receptor alpha. It binds to the IL-4α subunit which is a complex receptor shared by both IL-4 and IL-13.
Dupiliumab inhibits IL-4 signaling through Type 1 receptors while it inhibits both IL-4 and IL-13 signaling through Type 2 receptors.
Dupilumab inhibits IL-4 and IL-13 signalling
Where are IL-4α receptors present in the human body?
IL-4α is abundant in inflammatory cells such as mast cells, eosinophils, lymphocytes, and macrophages. It is also present in epithelial cells and goblet cells.
IL-4α receptor inhibition results in the inhibition of proinflammatory cytokines including cytokines, leukotrienes, histamine, chemokines, and eicosanoids), nitric oxide, and IgE.
How Dupilumab helps patients with asthma and Atopic dermatitis?
IL-4 helps in the differentiation and maturation of Th-2 cells and IgE switching in B lymphocytes from IgG1 to IgE. IL-13 is produced by Th-2 cells and is primarily involved in eosinophils chemotaxis that is primarily involved in the pathogenesis of allergic asthma [Ref]. It also is involved in the maturation and differentiation of B-lymphocytes and activation of macrophages.
IL-4 and IL-13 play important roles in downregulating important genes that are essential for skin healing and integrity. These cytokines also prevent the upregulation of peptides that are released in response to bacterial, fungal, and viral infections. This could result in increased susceptibility of the person to infections.
Dupilumab has also been observed to downregulate important chemokines that play a role in the pathogenesis of atopic dermatitis. These include TARC and CCL17. TARC is Thymus and activation-regulated chemokine. Along with these chemokines, it downregulates the cytokines that are associated with activation of eosinophils and T-cells activation, as well as epidermal hyperplasia-related genes [Ref].
Dupilumab is FDA-approved for the treatment of refractory asthma and Atopic dermatitis
In Conclusion:
IL-4 and IL-13 targeting is a novel treatment strategy utilized to control refractory disease states in patients with atopic dermatitis and allergic asthma. Dupilumab is FDA-approved for the treatment of patients with severe and refractory asthma and atopic dermatitis. It primarily targets the key cytokines (IL-4 and IL-13) involved in patients with these disorders.