Dupilumab – The First Biologic Umbrellaing Type 2 Inflammation Treatment: How Does It Work and Who Is It For?

The product is currently covered in the Czech Republic for adult patients with severe atopic dermatitis after the failure (insufficient efficacy) of at least one conventional systemic immunosuppressive therapy (excluding corticosteroids) or for those who cannot be treated with systemic therapy due to intolerance or contraindication.

Indications

• Atopic Dermatitis

The drug is indicated for the treatment of moderate to severe atopic dermatitis (AD) in adults and adolescents over 12 years of age who are suitable candidates for systemic therapy.

• Asthma

The drug can be used as an add-on maintenance treatment in adults and adolescents 12 years and older with severe asthma with type 2 inflammation characterized by elevated blood eosinophils and/or increased levels of exhaled nitric oxide (FE_NO), whose condition is not adequately controlled with high-dose inhaled corticosteroids and another maintenance therapy.

• Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP)

The drug can be used as add-on therapy to intranasal corticosteroids in adults with severe disease where systemic corticosteroid therapy and/or surgery have not provided adequate disease control.

Mechanism of Action

Dupilumab is a recombinant human monoclonal IgG4 antibody produced by recombinant DNA technology. It inhibits the interleukin 4 (IL-4) signaling pathway via the type I receptor (IL-4Rα/γc) and the IL-4 and IL-13 signaling pathway via the type II receptor (IL-4Rα/IL-13Rα). IL-4 and IL-13 are key drivers of type 2 inflammatory diseases in humans, such as AD, asthma, and chronic rhinosinusitis with nasal polyposis. Blocking the IL-4/IL-13 pathway with dupilumab leads to a reduction in a number of type 2 inflammation mediators.

Pharmacodynamics

In clinical studies of AD, treatment with dupilumab was associated with a reduction in the concentration of type 2 immunity biomarkers such as the chemokine TARC/CCL17 (thymus and activation-regulated chemokine), total serum IgE, and allergen-specific serum IgE. A reduction in lactate dehydrogenase (LDH), a biomarker associated with the activity and intensity of AD, was also observed.

In clinical studies, treatment with dupilumab in asthmatics led to a significant reduction in FE_NO and circulating concentrations of eotaxin 3, total IgE, allergen-specific IgE, TARC, and periostin compared to placebo. This reduction was comparable for both 200 mg and 300 mg regimens, administered once every 2 weeks. The values of these markers approached maximum suppression after 2 weeks of treatment, except for IgE, which decreased more slowly. These effects persisted throughout the treatment.

Where to Refer Patients with Severe Asthma and/or Severe Atopic Dermatitis?

Patients with severe asthma should be referred to one of the 13 centers operating at regional and university hospitals. A complete list can be found at the following link: www.tezke-astma.cz/index.php?pg=narodni-centrum-pro-tezke-astma. Experts in diagnosing and treating patients with severe asthma will assess complicating factors and comorbidities, confirm the diagnosis, and propose the most appropriate treatment plan, which may include biologic therapy not available through the patient's attending physician. Similarly, patients with severe atopic dermatitis should be referred to one of the 18 biologic treatment centers. The complete list, along with contact details, is available here: www.dermanet.cz/cs/kozni-ordinace/centra-biologicke-lecby.

(mir)

Sources:

1. Dupixent 300 mg inj. sol. 2× 2 ml Available at: www.ema.europa.eu/en/documents/product-information/dupixent-epar-product-information_en.pdf
2. Sedlák V. Difficult-to-treat asthma. Czech Initiative for Asthma, 2019. Available at: www.cipa.cz/tezke-a-obtizne-lecitelne-astma-bronchiale