Use of Targeted Therapy with Dupilumab in Patients with Allergic Diseases
Interleukins (IL) 4 and 13 play an important role in the pathogenesis of allergic diseases. Their blockade is therefore a suitable strategy for a number of these conditions. This is offered by the new monoclonal antibody dupilumab (Dupixent), which is approved for the treatment of atopic dermatitis, asthma with type 2 inflammation, and chronic rhinosinusitis with nasal polyposis. Studies are ongoing to evaluate its efficacy in other diseases where type 2 inflammation predominates.
Mechanism of Action of Dupilumab
Interleukins IL-4 and IL-13 are key cytokines involved in type 2 inflammatory response – inflammation associated with TH2 lymphocytes, secretion of pro-inflammatory interleukins, eosinophilia, and significant antibody production. IL-4 and IL-13 bind to receptors containing the IL-4Rα chain. Dupilumab is a human monoclonal antibody that blocks IL-4 and IL-13 signaling through IL-4Rα.
Indications and Efficacy
Atopic Dermatitis
In atopic dermatitis, dupilumab has demonstrated significant symptom alleviation in several global clinical trials and in real-world practice, including reduction of pruritus and improvement in sleep, subsequently reducing anxiety and depression and enhancing quality of life. Blocking interleukins improves the skin barrier by up-regulating genes coding for proteins involved in epidermal structure and also has an anti-itch effect. Dupilumab also reduces the risk of skin infection in patients with atopic dermatitis.
The drug is indicated for the treatment of moderate to severe atopic dermatitis in adults and adolescents aged 12 years and older who are candidates for systemic therapy. In the Czech Republic, it is funded for adult patients with severe atopic dermatitis after the failure of at least one form of conventional systemic immunosuppressive therapy (except corticosteroids) or for those who cannot use systemic therapy due to intolerance or contraindication. Dupilumab can be used with or without topical corticosteroids. Topical calcineurin inhibitors can also be used concurrently, but only for problematic areas.
Type 2 Inflammatory Asthma
Dupilumab has proven efficacy and safety in the treatment of refractory asthma, especially in patients with type 2 inflammation. It is indicated as add-on maintenance therapy for adults and adolescents aged 12 years and older with severe asthma characterized by elevated blood eosinophils or increased levels of exhaled nitric oxide, whose disease is not adequately controlled with high-dose inhaled corticosteroids and an additional maintenance medication.
Chronic Rhinosinusitis with Nasal Polyposis
Favorable phase III study results led to the approval of dupilumab for the treatment of adult patients with severe chronic rhinosinusitis with nasal polyposis. It is indicated as add-on therapy to intranasal corticosteroids when disease control is inadequate with systemic corticosteroids or surgery.
Administration of the Drug
Dupilumab is available in pre-filled syringes for subcutaneous administration every 2 weeks. Therapy should be initiated by a specialist experienced in treating conditions for which dupilumab is indicated.
Conclusion
In the Czech Republic, dupilumab can now be indicated as a funded treatment for adult patients with atopic dermatitis who fail to achieve remission with systemic immunosuppressive therapy or who do not tolerate it. General practitioners should refer such patients to a specialist (allergist, dermatologist, or clinical immunologist) for dupilumab therapy.
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Sources:
1. Matsunaga K., Katoh N., Fujieda S et al. Dupilumab: basic aspects and applications to allergic diseases. Allergol Int 2020; 69 (2): 187−196, doi: 10.1016/j.alit.2020.01.002.
2. SPC Dupixent. Available at: www.ema.europa.eu/en/documents/product-information/dupixent-epar-product-information_cs.pdf
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