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DUPIXENT is indicated as an add-on maintenance treatment in adult patients with inadequately controlled chronic rhinosinusitis with nasal polyposis or CRS with NP. CRS with NP is predominantly characterized by Type 2 inflammation of the nose and paranasal sinuses and is frequently associated with comorbidities. IL-4 and IL-13 are Type 2 cytokines that play key roles in CRS with NP, including Th2 cell differentiation, eosinophil trafficking, and B cell switching to IgE release. DUPIXENT is the first and only dual inhibitor of IL-4 and IL-13 signaling addressing Type 2 inflammation that contributes to CRS with NP. In the inflammatory process, IL-4 binds to the IL-4 receptor alpha subunit at the Type 1 receptor and IL-13 binds to the IL-13 receptor alpha 1 subunit at the Type 2 receptor. IL-4 can also bind to the IL-4 receptor alpha subunit at the Type 2 receptor, and each interaction transmits its own signal downstream. DUPIXENT binds to IL-4 receptor alpha subunit, blocking IL-4 and IL-13 intracellular signaling. This results in reduced expression of proinflammatory cytokines, ultimately leading to decreased total and specific IgE. In addition, there is an impact on eosinophil activation and trafficking, along with other mechanisms that decrease Type 2 inflammation. DUPIXENT is the first and only dual inhibitor of IL-4 and IL-13 signaling, two cytokines that contribute to underlying Type 2 inflammation in CRS with NP.
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, rash, erythema nodosum, anaphylaxis and serum sickness or serum sickness-like reactions, were reported in <1% of subjects who received DUPIXENT in clinical trials. If a clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue DUPIXENT.
Conjunctivitis and Keratitis: Conjunctivitis occurred more frequently in subjects with chronic rhinosinusitis with nasal polyposis who received DUPIXENT. There were no cases of keratitis reported in the CRSwNP development program. Advise patients to report new onset or worsening eye symptoms to their healthcare provider.
Eosinophilic Conditions: Patients being treated for asthma may present with serious systemic eosinophilia sometimes presenting with clinical features of eosinophilic pneumonia or vasculitis consistent with eosinophilic granulomatosis with polyangiitis (EGPA), conditions which are often treated with systemic corticosteroid therapy. These events may be associated with the reduction of oral corticosteroid therapy. Physicians should be alert to vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients with eosinophilia. Cases of eosinophilic pneumonia were reported in adult patients who participated in the asthma development program and cases of vasculitis consistent with EGPA have been reported with DUPIXENT in adult patients who participated in the asthma development program as well as in adult patients with co-morbid asthma in the CRSwNP development program. A causal association between DUPIXENT and these conditions has not been established.
Reduction of Corticosteroid Dosage: Do not discontinue systemic, topical, or inhaled corticosteroids abruptly upon initiation with DUPIXENT. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.
Patients with Co-Morbid Asthma: Advise patients with co-morbid asthma not to adjust or stop their asthma treatments without consultation with their physicians.
Parasitic (Helminth) Infections: It is unknown if DUPIXENT will influence the immune response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with DUPIXENT. If patients become infected while receiving treatment with DUPIXENT and do not respond to anti-helminth treatment, discontinue treatment with DUPIXENT until the infection resolves.
ADVERSE REACTIONS: The most common adverse reactions (incidence ≥1%) in patients with CRSwNP are injection site reactions, eosinophilia, insomnia, toothache, gastritis, arthralgia, and conjunctivitis.
DRUG INTERACTIONS: Avoid use of live vaccines in patients treated with DUPIXENT.
USE IN SPECIFIC POPULATIONS
- Pregnancy: There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to DUPIXENT during pregnancy. Healthcare providers and patients may call 1-877-311-8972 or go to https://mothertobaby.org/ongoing-study/dupixent/ to enroll in or obtain information about the registry. Available data from case reports and case series with DUPIXENT use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. 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. Maternal 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 as an add-on maintenance treatment in adult patients with inadequately controlled chronic rhinosinusitis with nasal polyposis (CRSwNP).
DUPIXENT Targets Upper and Lower Airway Inflammation in CRSwNP and Asthma
DUPIXENT is the first and only dual inhibitor of IL-4 and IL-13 signaling, two cytokines that contribute to underlying Type 2 inflammation in CRSwNP1,2,a
CRSwNP is predominantly characterized by Type 2 inflammation of the nose and paranasal sinuses and is frequently associated with comorbidities of the lower airway.2,5-7
a The mechanism of dupilumab action in asthma has not been established.
DUPIXENT is indicated as an add-on maintenance treatment in patients with moderate-to-severe asthma aged 12 years and older with an eosinophilic phenotype or with oral corticosteroid dependent asthma. Limitation of Use: DUPIXENT is not indicated for the relief of acute bronchospasm or status asthmaticus.