What is the recommended use and dosing of Dupixent (dupilumab)?

Dupixent (Dupilumab): Recommended Use and Dosing

Dupixent is a subcutaneous monoclonal antibody targeting the IL-4 receptor α subunit that blocks IL-4 and IL-13 signaling, approved for multiple type 2 inflammatory conditions with specific dosing regimens based on indication, age, and weight. 1

Mechanism of Action

Dupilumab is a fully human IgG4 monoclonal antibody that binds to and blocks the IL-4 receptor α subunit, which is shared by both type I IL-4 and type II IL-4/IL-13 receptor complexes. 2 This dual inhibition targets key drivers of type 2 inflammation involved in IgE synthesis, eosinophil activation, mucus secretion, and airway remodeling. 3

FDA-Approved Indications and Dosing

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)

For adults and pediatric patients ≥12 years: 300 mg subcutaneously every 2 weeks (no loading dose required). 1

• Dupilumab is the only monoclonal antibody approved for CRSwNP treatment and should be used in patients fulfilling criteria for monoclonal antibody therapy. 3
• Use as add-on to standard intranasal corticosteroid therapy in patients with severe, inadequately controlled disease. 3
• Demonstrated clinically significant improvements at 4-6 months in:
  • SNOT-22 scores (mean difference -19.61,95% CI -22.53 to -16.69) 3
  • Nasal polyp scores (mean difference -1.79,95% CI -2.01 to -1.56) 3
  • Smell restoration via UPSIT (mean difference 10.83,95% CI 9.59 to 12.08) 3
  • Nasal congestion scores (mean difference -0.86,95% CI -0.98 to -0.75) 3
  • Lund-Mackay CT scores (SMD -1.50,95% CI -1.84 to -1.16) 3

Atopic Dermatitis

Adults: 600 mg loading dose (two 300 mg injections), then 300 mg every 2 weeks. 1

Pediatric patients 6 months to 5 years:

• 5 to <15 kg: 200 mg every 4 weeks 1
• 15 to <30 kg: 300 mg every 4 weeks 1

Pediatric patients ≥6 years:

• 15 to <30 kg: 600 mg loading dose, then 300 mg every 4 weeks 1
• 30 to <60 kg: 400 mg loading dose, then 200 mg every 2 weeks 1
• ≥60 kg: 600 mg loading dose, then 300 mg every 2 weeks 1

Asthma

Adults and pediatric patients ≥12 years:

• Standard dosing: 400 mg loading dose, then 200 mg every 2 weeks OR 600 mg loading dose, then 300 mg every 2 weeks 1
• For oral corticosteroid-dependent asthma, co-morbid moderate-to-severe atopic dermatitis, or co-morbid CRSwNP: 600 mg loading dose, then 300 mg every 2 weeks 1

Pediatric patients 6-11 years:

• 15 to <30 kg: 300 mg every 4 weeks 1
• ≥30 kg: 200 mg every 2 weeks 1
• For co-morbid moderate-to-severe atopic dermatitis: use loading dose per Table 2 1

Eosinophilic Esophagitis

Patients ≥1 year and ≥15 kg:

• 15 to <30 kg: 200 mg every 2 weeks 1
• 30 to <40 kg: 300 mg every 2 weeks 1
• ≥40 kg: 300 mg every week 1

Prurigo Nodularis

Adults: 600 mg loading dose, then 300 mg every 2 weeks. 1

Chronic Obstructive Pulmonary Disease

Adults: 300 mg every 2 weeks (no loading dose). 1

Chronic Spontaneous Urticaria

Adults: 600 mg loading dose, then 300 mg every 2 weeks. 1

Pediatric patients 12-17 years:

• 30 to <60 kg: 400 mg loading dose, then 200 mg every 2 weeks 1
• ≥60 kg: 600 mg loading dose, then 300 mg every 2 weeks 1

Bullous Pemphigoid

Adults: 600 mg loading dose, then 300 mg every 2 weeks, used in combination with a tapering course of oral corticosteroids. 1

Critical Safety Considerations

Ocular Surface Disorders

Before initiating dupilumab in atopic dermatitis patients, screen for pre-existing eye disease, particularly dry eye disease with keratitis and eyelid eczema, as these significantly increase DROSD risk. 3

• Refer to ophthalmology (routine pathway) patients with significant current or chronic corneal/conjunctival disease before starting dupilumab. 3
• Delay dupilumab for patients with corneal transplant history until ophthalmology discussion, or for acute reversible eye conditions (e.g., infectious conjunctivitis) until resolution. 3
• Pre-existing dry eye disease with keratitis increases DROSD risk (OR 6.3, CI 1.3-31.6). 3
• Eyelid eczema increases DROSD risk (OR 8.7, CI 1.8-40.6). 3
• DROSD risk is specific to atopic dermatitis patients; comparable rates to placebo occur in asthma, CRSwNP, and eosinophilic esophagitis. 3
• Conjunctivitis occurs in atopic dermatitis trials but not in asthma or CRSwNP trials. 3

General Adverse Events

In CRSwNP trials, the most common adverse events (nasopharyngitis, worsening nasal polyps and asthma, headache, epistaxis, injection-site erythema) were more frequent with placebo than dupilumab. 3

Clinical Efficacy in CRSwNP

Dupilumab demonstrates sustained efficacy in severe CRSwNP patients who have failed intranasal corticosteroids and often previous surgery. 4

• Significant improvements maintained through 52 weeks with every-2-week dosing. 3
• Benefits observed regardless of comorbid asthma, NSAID-exacerbated respiratory disease, or previous surgery history. 4
• In patients with comorbid asthma, dupilumab improved FEV1 (mean difference 0.21 L, 95% CI 0.20-0.22) and asthma control regardless of baseline eosinophil count. 3
• Reduces need for systemic corticosteroids and nasal polyp surgery. 2, 4

Administration

All dupilumab formulations are administered by subcutaneous injection. 1 The medication can be self-administered after proper training or given by a healthcare provider. 1