Specifically Targets a Source of Underlying Inflammation in Atopic Dermatitis

IL-4 and IL-13 are important in the development of Type 2 inflammation and its downstream effects.1-3

Multiple cell types that express IL-4Rα (eg, mast cells, eosinophils, macrophages, lymphocytes, epithelial cells) and inflammatory mediators (eg, histamine, eicosanoids, leukotrienes, cytokines, chemokines) are involved in Type 2 inflammation.1

DUPIXENT inhibits signaling of IL-4 and IL-13, Type 2 cytokines1,2


Inhibits IL-4 and IL-13 cytokine‑induced responses, including the release of1:

  • Proinflammatory cytokines and chemokines
  • IgE

The first treatment of its kind to target IL-4 and IL-13 receptor signaling1

Atopic dermatitis, or AD, is a chronic inflammatory skin disease that leads to dry, scaly, itchy skin and eczematous lesions. Moderate-to-severe AD is a potentially debilitating disease. The pathophysiology of AD is complex and multifactorial, involving immune and epidermal barrier components influenced by genetic and environmental factors. Patients with AD have a mix of lesional and nonlesional skin.

Although normal-looking, nonlesional skin has persistent underlying inflammation due to activation of the immune system. In patients with AD, there are 2 main converging pathophysiological features: increased skin inflammation coupled with abnormalities of epidermal barrier structures and function.

Antigens are recognized by resident cells such as Langerhans cells and innate lymphoid Type 2 cells and are presented to T cells in the skin and in lymph nodes driving immune inflammatory response in AD. This results in the initiation of a Type 2 including Th2, immune response, such as IL-4, IL-13, and IL-31 release of chemokines. Cytokines that were historically known as Th2 cytokines, such as IL-4 and IL-13, are also produced by other cell types, including ILC2s, eosinophils, mast cells, basophils, and macrophages and are thus now known as Type 2 cytokines.

In the acute phase of lesion development there is an increase in T cells and continued release of the Type 2 cytokines IL-4 and IL-13, along with other cytokines and chemokines that promote inflammation. As the lesion progresses due to chronic disease, there is persistent Type 2, including Th2, signaling.

IL-4 and IL-13 are cytokines involved in the development of AD and play roles in the regulation of the immune response. IL-4 and IL-13 signal mainly through 2 receptor complexes.

The Type I receptor, consisting of IL-4Rα and γ-chain subunits, only binds IL-4. The Type II receptor, consisting of IL-4Rα and IL-13Rα1 subunits, is the primary receptor for IL-13 but also binds IL-4. In AD, increased levels of IL-4 and IL-13 lead to amplified signaling of Type 2 cytokines and chemokines and activation of subsequent proinflammatory signaling pathways.

Dupilumab is a human monoclonal antibody that binds specifically to the IL-4Rα subunit of the receptor complexes for IL-4 and IL-13, two Type 2 cytokines that play roles in the pathogenesis of AD. Dupilumab inhibits IL-4 signaling via the Type I receptor and both IL-4 and IL-13 signaling through the Type II receptor resulting in decreased IL-4 and IL-13 cytokine-induced responses, including the release of proinflammatory cytokines, chemokines, and IgE.

Identifying Adult Patients DUPIXENT may be an appropriate treatment for adults with uncontrolled moderate-to-severe atopic dermatitis. Identify Adult Patients
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Reference:
References:
  1. DUPIXENT Prescribing Information. March 2019.
  2. Simpson EL, Bieber T, Guttman-Yassky E, et al; SOLO 1 and SOLO 2 Investigators. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335-2348.
  3. Blauvelt A, de Bruin-Weller M, Gooderham M, et al. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet. 2017;389(10086):2287-2303.
  4. Data on file, Regeneron Pharmaceuticals, Inc.
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  11. Data on file, Regeneron Pharmaceuticals, Inc.
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  13. Simpson EL, Bieber T, Guttman-Yassky E, et al; SOLO 1 and SOLO 2 Investigators. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335-2348.
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  34. Data on file, Regeneron Pharmaceuticals, Inc.
  35. DUPIXENT Prescribing Information. March 2019.
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  37. DUPIXENT Prescribing Information. March 2019.
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  39. Data on file, Regeneron Pharmaceuticals, Inc.