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DUPIXENT Targets Immune Mediators Within the Type 2 Pathway Associated with Atopic Dermatitis1,2

IL-4 and IL-13 signaling contribute to perpetuating underlying Type 2 inflammation1-5


IL-4 and IL-13, among other Type 2 cytokines, lead to1,4-7:

  • IgE production
  • Weakening of the epidermal barrier, including reduction in antimicrobial peptides
  • Recruitment of mast cells and eosinophils

Helps Repair the Skin By Specifically Targeting a Source of Type 2 Inflammation1,2,4,8

DUPIXENT is the first and only treatment of its kind to inhibit the signaling of IL-4 and IL-13, Type 2 cytokines1,2

HOW DUPIXENT WORKS

DUPIXENT targets immune mediators within the Type 2 pathway associated with atopic dermatitis.1,2
Watch the video to see how it works.

Transcript

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.

Though 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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References:
  1. DUPIXENT Prescribing Information.
  2. Gandhi NA, Bennett BL, Graham NMH, Pirozzi G, Stahl N, Yancopoulos GD. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35-50.
  3. Kaiko G, Horvat J, Beagley K, et al. Immunological decision-making: how does the immune system decide to mount a helper T-cell response? Immunology. 2008;123(3):326-338.
  4. Guttman-Yassky E, Bissonnette R, Ungar B. et al. Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis. J Allergy Clin Immunol. 2019;143(1):155-172.
  5. Guttman-Yassky E, Nograles KE, Krueger JG. Contrasting pathogenesis of atopic dermatitis and psoriasis—part II: immune cell subsets and therapeutic concepts. J Allergy Clin Immunol. 2011;127(3):1420-1432.
  6. Eyerich K, Eyerich S. Immune response patterns in non-communicable inflammatory skin diseases. J Eur Acad Dermatol Venereol. 2017;32(5):629-703.
  7. Albanesi C, Fairchild HR, Madonna S, et al. IL-4 and IL-13 negatively regulate TNF-alpha- and IFN-gamma-induced beta-defensin expression through STAT-6, suppressor of cytokine signaling (SOCS)-1, and SOCS-3. J Immunol. 2017;179(2):984-992.
  8. Callewaert C, Nakatsuji T, Knight R, et al. IL-4Rα blockade by dupilumab decreases staphylococcus aureus colonization and increases microbial diversity in atopic dermatitis [published online June 25, 2019]. J Invest Dermatol. doi:10.1016/j.jid.2019.05.024