What is Dupixent (Dupilumab)?
Dupixent (dupilumab) is a fully human monoclonal antibody that blocks the interleukin-4 receptor α (IL-4Rα) subunit, inhibiting both IL-4 and IL-13 signaling pathways to reduce type 2 inflammation in multiple diseases including chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis, and asthma. 1, 2
Mechanism of Action
Dupilumab works through a specific mechanism:
- Targets the IL-4 receptor α subunit shared by IL-4 and IL-13 receptor complexes 2
- Blocks both IL-4 signaling via Type I receptor and IL-4/IL-13 signaling through Type II receptor 2
- Inhibits type 2 inflammation by preventing these cytokines from activating inflammatory pathways 3
- Reduces inflammatory mediators including proinflammatory cytokines, chemokines, and IgE 2
FDA-Approved Indications
Dupixent is FDA-approved for:
- Moderate-to-severe atopic dermatitis in adults and children 6 months and older
- Maintenance treatment of moderate-to-severe asthma in adults and children 6 years and older
- Maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in adults and children 12 years and older
- Eosinophilic esophagitis (EoE) in adults and children 1 year and older weighing at least 15 kg
- Prurigo nodularis (PN) in adults
- Maintenance treatment of inadequately controlled chronic obstructive pulmonary disease (COPD) in adults with high eosinophil counts
- Chronic spontaneous urticaria (CSU) in adults and children 12 years and older
- Bullous pemphigoid (BP) in adults 2
Clinical Efficacy in CRSwNP
In phase 3 clinical trials, dupilumab demonstrated significant improvements in:
- SNOT-22 scores (quality of life measure) with a mean decrease of 19.61 points 1
- Rhinosinusitis disease severity (VAS) with a mean decrease of 2.54 1
- Nasal congestion/obstruction scores with a mean decrease of 0.86 1
- Smell function (UPSIT score) with a mean improvement of 10.83 points 1
- Nasal polyp score with a mean decrease of 1.79 1
- CT scan findings (Lund-Mackay score) with significant improvement 1
- Lung function (FEV1) in patients with comorbid asthma 1, 4
Administration and Dosing
- Administered as a subcutaneous injection
- For CRSwNP: typically 300 mg every two weeks 1, 2
- Used as add-on therapy to intranasal corticosteroids in patients with inadequately controlled disease 4
Safety Profile
The most common adverse events include:
- Nasopharyngitis
- Injection site reactions
- Headache
- Epistaxis (nosebleed)
Notably, adverse events were actually more frequent with placebo than with dupilumab in CRSwNP trials 1
Important safety considerations:
- Conjunctivitis and keratitis may occur (more common in atopic dermatitis than in CRSwNP) 2
- Potential for eosinophilic conditions (monitor for eosinophilic pneumonia or eosinophilic granulomatosis with polyangiitis) 2
- Live vaccines should not be given immediately before or during treatment 2
- New-onset psoriasis has been reported 2
- Potential for helminth (parasitic) infections 2
Clinical Positioning
Dupilumab is the first monoclonal antibody approved for CRSwNP treatment 1. The European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS 2020) recommends dupilumab for patients with CRSwNP who fulfill criteria for biologic therapy, particularly those with:
- Severe, inadequately controlled disease despite standard treatments
- Comorbid conditions like asthma or NSAID-exacerbated respiratory disease
- History of previous nasal polyp surgery with recurrence 1, 4
Dupilumab is particularly valuable for patients with multiple type 2 inflammatory conditions (like concurrent CRSwNP and atopic dermatitis or asthma) as it can effectively treat these conditions simultaneously 5.
Human Immunoglobulin G4 (IgG4) structure of dupilumab allows for minimal immune system activation while effectively blocking the target receptor, contributing to its favorable safety profile 6.
In summary, Dupixent represents a significant advancement in treating type 2 inflammatory conditions, offering targeted therapy that addresses the underlying pathophysiology rather than just managing symptoms.