What is Dupixent (dupilumab)?

What is Dupixent (Dupilumab)?

Dupixent (dupilumab) is a fully human monoclonal antibody that blocks interleukin-4 receptor alpha (IL-4Rα), thereby inhibiting both IL-4 and IL-13 signaling pathways that drive type 2 inflammatory diseases. 1

Mechanism of Action

Dupilumab works by specifically binding to the IL-4Rα subunit, which is shared by both Type I (IL-4 only) and Type II (IL-4 and IL-13) receptor complexes. 2, 1 By blocking this receptor, dupilumab prevents the downstream inflammatory cascade that characterizes multiple allergic and inflammatory conditions. 3

Key molecular effects include:

• Inhibition of IgE synthesis by blocking IL-4 and IL-13-mediated B cell class switching 2
• Prevention of eosinophil activation, chemotaxis, and tissue infiltration 2
• Blockade of mucus hypersecretion from goblet cells 2
• Prevention of airway remodeling by inhibiting fibroblast and smooth muscle cell proliferation 2
• Restoration of epidermal barrier function by reversing IL-4/IL-13-induced downregulation of filaggrin in keratinocytes 2
• Reduction of proinflammatory mediators including IL-5, IL-9, IL-13, TARC, and eotaxin 2

FDA-Approved Indications

Dupixent is administered as a subcutaneous injection and is approved for multiple type 2 inflammatory conditions: 1

Atopic Dermatitis:

• Adults and children ≥6 months with moderate-to-severe disease inadequately controlled by topical therapies 1, 4

Asthma:

• Adults and children ≥6 years with moderate-to-severe asthma as add-on maintenance therapy 1, 3
• Helps prevent severe exacerbations and improves lung function 1
• May reduce oral corticosteroid requirements 1

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP):

• Adults and children ≥12 years with inadequately controlled disease 1, 5
• Dupilumab is the only monoclonal antibody approved for CRSwNP treatment 6

Eosinophilic Esophagitis (EoE):

• Adults and children ≥1 year weighing at least 15 kg (33 lbs) 1

Prurigo Nodularis (PN):

• Adults with this chronic inflammatory skin condition 1

Chronic Obstructive Pulmonary Disease (COPD):

• Adults with inadequately controlled COPD and elevated blood eosinophils 1
• Reduces exacerbations and improves breathing 1

Clinical Efficacy in CRSwNP

In two pivotal phase III trials involving 784 participants with severe CRSwNP, dupilumab 300 mg every 2 weeks added to intranasal corticosteroids demonstrated: 6

• SNOT-22 score reduction: Mean difference -19.61 (95% CI -22.53 to -16.69), clinically significant improvement 6
• Nasal polyp score reduction: Mean difference -1.79 (95% CI -2.01 to -1.56) from baseline of ~6 (severe disease) 6
• Smell improvement (UPSIT): Mean difference 10.83 (95% CI 9.59 to 12.08) 6
• Nasal congestion reduction: Mean difference -0.86 (95% CI -0.98 to -0.75) 6
• Lung function improvement in comorbid asthma: FEV1 increase of 0.21 L (95% CI 0.20 to 0.22) 6

Benefits were sustained at 4-6 months and occurred regardless of comorbid asthma, NSAID-exacerbated respiratory disease, or prior nasal polyp surgery history. 5

Comparative Efficacy Among Biologics

Among biologics for CRSwNP, dupilumab and omalizumab demonstrate the greatest benefits for patient-important outcomes, followed by mepolizumab. 6 The 2023 Joint Task Force guidelines note that dupilumab shows higher certainty and magnitude of benefit compared to other available biologics. 6

Safety Profile

Common adverse events (which were actually more frequent with placebo in CRSwNP trials): 6

• Nasopharyngitis
• Headache
• Epistaxis
• Injection-site erythema

Important adverse events to monitor: 6, 1, 7

• Conjunctivitis and keratitis: Occurs in 32-55% of patients, particularly noted in atopic dermatitis trials 6, 7
• Eosinophilic conditions: Potential for eosinophilic pneumonia or vasculitis consistent with eosinophilic granulomatosis with polyangiitis 1
• Head and neck dermatitis, psoriatic lesions, alopecia areata 7
• Arthralgia: New or worsening joint symptoms should be reported 1

Critical safety considerations: 1

• Not for acute asthma or COPD symptoms
• Avoid live vaccines during treatment
• Treat helminth infections before initiating therapy
• Do not abruptly discontinue corticosteroids
• Ophthalmologic examination recommended before initiation 7

Clinical Positioning

For CRSwNP, dupilumab should be considered in patients who have not adequately responded to intranasal corticosteroids and/or surgery. 6 The 2023 guidelines suggest biologics (conditional recommendation) for patients with high disease severity who would value the higher certainty and magnitude of benefits over less invasive therapies. 6

Patients with multiple type 2 inflammatory comorbidities (e.g., atopic dermatitis plus CRSwNP, or asthma plus CRSwNP) may particularly benefit from dupilumab's dual indication coverage, improving compliance and reducing healthcare costs. 8