DUPIXENT is the first biologic for adult patients with uncontrolled moderate‑to‑severe atopic dermatitis.1-3
An Injectable Biologic, Inhibitor of IL-4 and IL-13 Signaling1
DUPIXENT is the first biologic for adults with uncontrolled moderate‑to‑severe atopic dermatitis. It is the first treatment of its kind and targets the signaling of IL-4 and IL-13, two of the cytokines involved in the underlying inflammatory process.1,4
IL-4 and IL-13 are two of the Th2 cytokines involved in the underlying inflammatory process in atopic dermatitis.1,4 Increased signaling of IL-4 and IL-13 leads to amplified signaling of Th2 cytokines and chemokines and the activation of subsequent proinflammatory signaling pathways.5
The relationship between the pharmacodynamic activity and the mechanism(s) by which dupilumab exerts its clinical effects is unknown.1
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 two 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 critical roles in the regulation of the immune response. IL-4 and IL-13 signal mainly through two 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.
Important Safety Information and Indication
CONTRAINDICATION: DUPIXENT is contraindicated in patients with known hypersensitivity to dupilumab or any of its excipients.
WARNINGS AND PRECAUTIONS
Hypersensitivity: Hypersensitivity reactions, including generalized urticaria and serum sickness or serum sickness-like reactions, were reported in <1% of subjects who received DUPIXENT. If a clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue DUPIXENT.
Conjunctivitis and Keratitis: Conjunctivitis and keratitis occurred more frequently in subjects who received DUPIXENT. Conjunctivitis was the most frequently reported eye disorder. Advise patients to report new onset or worsening eye symptoms to their healthcare provider.
Comorbid Asthma: Safety and efficacy of DUPIXENT have not been established in the treatment of asthma. Advise patients with comorbid asthma not to adjust or stop their asthma treatments without consultation with their healthcare provider.
Parasitic (Helminth) Infections: Patients with known helminth infections were excluded from participation in clinical studies. It is unknown if DUPIXENT will influence the immune response against helminth infections.
ADVERSE REACTIONS: The most common adverse reactions (incidence ≥1%) are injection site reactions, conjunctivitis, blepharitis, oral herpes, keratitis, eye pruritus, other herpes simplex virus infection, and dry eye.
DRUG INTERACTIONS: Avoid use of live vaccines in patients treated with DUPIXENT.
USE IN SPECIFIC POPULATIONS
Pregnancy: There are no available data on DUPIXENT use in pregnant women to inform any drug associated risk. Human IgG antibodies are known to cross the placental barrier; therefore, DUPIXENT may be transmitted from the mother to the developing fetus.
Lactation: There are no data on the presence of DUPIXENT in human milk, the effects on the breastfed infant, or the effects on milk production. Human IgG is known to be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for DUPIXENT and any potential adverse effects on the breastfed child from DUPIXENT or from the underlying maternal condition.
Please see accompanying full Prescribing Information
DUPIXENT is indicated for the treatment of adult patients with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. DUPIXENT can be used with or without topical corticosteroids.
In atopic dermatitis, increased signaling of IL-4 and IL-13 leads to5:
DUPIXENT is a human monoclonal antibody that inhibits the signaling of Th2 cytokines IL-4 and IL-131