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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 DUPIXENT Patients DUPIXENT may be an appropriate treatment for patients aged 12 years and older with uncontrolled moderate-to-severe atopic dermatitis. Identify Patients
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EASI, Eczema Area and Surface Index; IGA, Investigator’s Global Assessment; NRS, numerical rating scale; Q2W, once every 2 weeks; TCS, topical corticosteroids.

Reference:
References:
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  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.
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  11. Data on file, Regeneron Pharmaceuticals, Inc.
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  17. Data on file, Regeneron Pharmaceuticals, Inc.
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  47. Data on file, Regeneron Pharmaceuticals, Inc.
  48. DUPIXENT Prescribing Information.
  49. Blauvelt A, Simpson EL, Tyring SK, et al. Dupilumab does not affect correlates of vaccine‑induced immunity: a randomised, placebo‑controlled trial in adults with moderate‑to‑severe atopic dermatitis. J Am Acad Dermatol. 2019;80(1):158‑167.
  50. DUPIXENT Prescribing Information.
  51. Data on file, Regeneron Pharmaceuticals, Inc.
  52. Phan NQ, Blome C, Fritz F, et al. Assessment of pruritus intensity: prospective study on validity and reliability of the visual analogue scale, numerical rating scale and verbal rating scale in 471 patients with chronic pruritus. Acta Derm Venereol. 2012;92(5):502‑507.
  53. DUPIXENT Prescribing Information.
  54. Data on file, Regeneron Pharmaceuticals, Inc.
  55. Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M; the EASI evaluator group. The eczema area and severity (EASI): assessment of reliability in atopic dermatitis. Exp Dermatol. 2001;10(1):11‑18.
  56. EASI User Guide. HOME–Harmonising Outcome Measures for Eczema website. http://www.homeforeczema.org/documents/easi-user-guide-jan-2017-v3.pdf. Accessed January 4, 2019.
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