Mechanism of Action

• Fully human IgG4 Monoclonal antibody that inhibits IL4 receptor alpha subunit of heterodimeric IL4 and IL13 receptor, thus inhibiting IL4 and IL13 signaling and reducing Th2 mediated inflammation
• IL4 and IL13 can activate and promote survival of Th2
• Th2 response is implicated in the following:
  • Suppress terminal differentiation of proteins such as filaggrin
  • Inhibits antimicrobial peptide
  • Upregulation of S100As
  • Induction of epidermal hyperplasia
  • Suppression of lipid synthesis
  • Induction of spongiosis
• Also reduces CCL17, (thymus activating regulated chemokines) a key regulator of Th2
• Dupilumab effects
  • Downregulation of markers of epidermal proliferation
  • Downregulation of inflammatory mediators 
  • Upregulation of structural protein
  • Upregulation of lipid metabolism protein 
  • Upregulation of epidermal barrier proteins

Dose

• Subcutaneous
• Adult: loading dose of 600 mg then 300 mg every 2 weeks

Approval

• FDA approved for 6 years old and more with moderate to severe atopic dermatitis not adequately controlled with topical treatment 
• Off label: bullous pemphigoid

Side effects

• Nasopharyngitis
• URTI
• Injection site reaction (MC)
• Skin infection
• Exacerbation of atopic dermatitis
• Hypersensitivity reaction
• Oral HSV (3rd MC)
• Conjunctivitis in 10% of patients (2nd MC)

Management for conjunctivitis

• Monitor for conjunctival injection/ocular symptoms and screen for ocular symptoms before starting dupilumab
• Mild:
  • Lubricating eye drops
• Moderate to severe:
  • Ophthalmological referral 
  • Corticosteroid eyedrops 
  • Cyclosporin eyedrops 
  • Decrease Dupilumab dose/frequency 
  • Discontinue Dupilumab if persistent despite treatment

Notes

• Bioavailability 64%
• 7% develop antibody; some patients with severe antibodies develop serum sickness or serum sickness like reaction
• Avoid using with live vaccine
• Contraindicated in patient with hypersensitivity
• No assigned pregnancy category
• 50% EASI75