What is the recommended use and dosage of Dupilumab (dupilumab) for patients with atopic dermatitis and asthma?

Dupilumab Dosage and Use in Atopic Dermatitis and Asthma

Dupilumab is strongly recommended as the first-line systemic therapy for adults with moderate to severe atopic dermatitis, with a standard dosing of 600 mg subcutaneously at initiation, followed by 300 mg every 2 weeks, and for asthma patients, dosing is weight-based with 200-300 mg every 2 weeks. 1

Atopic Dermatitis Recommendations

Adult Dosing

• Initial dose: 600 mg subcutaneously (loading dose)
• Maintenance dose: 300 mg subcutaneously every 2 weeks 1
• Efficacy: Achieves 75% improvement in eczema severity (EASI-75) in 59-64% of patients by week 16 2

Pediatric Dosing

• Children ≥30 kg: 200 mg subcutaneously every 2 weeks
• Children <30 kg: 300 mg subcutaneously every 4 weeks 2

Clinical Efficacy

• Dupilumab has demonstrated sustained efficacy for up to 5 years in adults with moderate to severe atopic dermatitis 3
• At week 260 (5 years) of continuous treatment:
  • 67.5% of patients achieved clear or almost clear skin (IGA score 0-1)
  • 88.9% achieved at least 75% improvement in EASI score 3
• Mean EASI score decreased from 16.39 at baseline to 2.75 at end of study 3

Asthma Recommendations

• Dupilumab has shown efficacy in patients with moderate to severe asthma
• In patients with both atopic dermatitis and asthma, dupilumab treatment resulted in:
  • Significant improvement in FEV1 from 2.39 L at baseline to 2.60 L after 6 months of treatment
  • Improvement in FEV1pred% from 74.10% at baseline to 77.20% after 6 months 4
  • Significant improvements in Asthma Control Test (ACT) and Mini-Asthma Quality of Life Questionnaire (Mini-AQLQ) scores at 3,6, and 12 months 4

Mechanism of Action

Dupilumab is a monoclonal antibody that:

• Blocks interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling by binding to the IL-4 receptor alpha subunit
• Reduces inflammation by inhibiting Th2 immune responses
• Improves skin barrier function in atopic dermatitis 2, 5

Safety Profile

Common Adverse Effects

• Nasopharyngitis
• Upper respiratory tract infection
• Injection site reactions
• Conjunctivitis (6-26% of patients) - most significant adverse effect 2, 3
• Headache 3

Ocular Complications

• Dupilumab-related ocular surface disorders (DROSD) occur in approximately 5-26% of patients 2
• Risk factors include higher baseline AD severity, elevated eosinophil count, facial/eyelid eczema, and elevated IgE 2
• Patients with pre-existing eye conditions should be referred to ophthalmology before starting treatment 2

Monitoring

• No routine laboratory monitoring required 2
• No routine ophthalmology monitoring required in patients without pre-existing eye conditions 2
• Patients should be educated to report eye symptoms promptly 2

Pre-Treatment Assessment

• Evaluate for pre-existing eye conditions
• Refer to ophthalmology if significant corneal/conjunctival disease, history of corneal transplant, keratoconus, dry eye disease with keratitis, or eyelid eczema is present 2
• No routine laboratory testing required before initiating therapy 2

Treatment Algorithm for Atopic Dermatitis

1. First-line therapy: Optimize topical treatments (corticosteroids, calcineurin inhibitors)
2. If inadequate response: Consider dupilumab as first-line systemic therapy 1
   • All guideline workgroup members favored dupilumab as first-line systemic agent 1
3. For patients with both AD and asthma: Dupilumab provides benefits for both conditions simultaneously 4

Management of Ocular Complications

• Mild DROSD: Preservative-free ocular lubricants 2-4 times daily
• Moderate DROSD: Add topical antihistamine eyedrops (e.g., olopatadine)
• Severe DROSD: Urgent ophthalmology referral within 24 hours 2

Long-term Safety

Dupilumab has demonstrated an excellent safety profile over more than 5 years of follow-up, with exposure-adjusted rates of treatment-emergent adverse events generally stable or declining throughout long-term treatment 3.

Clinical Pearls and Pitfalls

• Pearl: Dupilumab can be used as monotherapy or in combination with topical corticosteroids for enhanced efficacy 5
• Pitfall: Delayed referral for ocular symptoms can lead to preventable complications 2
• Pearl: Baseline ophthalmology assessment has been shown to reduce DROSD incidence from 28% to 12% when pre-existing conditions are treated before starting dupilumab 2
• Pitfall: Patients may discontinue therapy due to conjunctivitis; early management is key to maintaining treatment benefits

In conclusion, dupilumab represents a significant advancement in the treatment of moderate-to-severe atopic dermatitis and asthma, with strong evidence supporting its efficacy and safety profile. Its ability to target the underlying inflammatory pathways makes it particularly valuable for patients with both conditions.