What is the role of Dupilumab (dupilumab) in the treatment of atopic dermatitis?

Dupilumab in Atopic Dermatitis

Dupilumab is the first-line systemic therapy for adults with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies, with all American Academy of Dermatology guideline workgroup members favoring it over other systemic agents. 1

Indications and Patient Selection

FDA-approved indications:

• Adults and children ≥6 months with moderate-to-severe atopic dermatitis inadequately controlled by topical prescription therapies or when those therapies are not advisable 2
• Can be used with or without topical corticosteroids 2

Key patient characteristics warranting dupilumab:

• Disease affecting multiple body areas, particularly sensitive locations (face, ears) that significantly impact quality of life 3
• Inadequate response to optimized topical therapy including topical corticosteroids and calcineurin inhibitors 1
• Substantial impairment in quality of life despite topical management 1

Mechanism and Efficacy

Mechanism of action:

• Fully human IgG4 monoclonal antibody targeting the IL-4 receptor α subunit 1
• Blocks signaling from both IL-4 and IL-13 by preventing formation of IL-4 and IL-13 receptor complexes 1, 4

Clinical efficacy:

• Standard dosing: 600 mg subcutaneously at initiation, then 300 mg every 2 weeks 1
• Achieves EASI 75 (≥75% reduction in Eczema Area Severity Index) in 63-64% of patients at 16 weeks when combined with topical corticosteroids 1
• Significantly improves signs, symptoms, quality of life, itch, and sleep compared to placebo (p<0.001) 1
• Real-world data shows pooled EASI 75 of 59% at 16 weeks across 908 patients 1

Comparative efficacy:

• Somewhat less efficacious than higher doses of JAK inhibitors (abrocitinib 200 mg, upadacitinib 30 mg) 1
• Better efficacy than abrocitinib 100 mg daily 1
• Comparable efficacy to upadacitinib 15 mg daily 1
• More effective than tralokinumab at 16 weeks based on network meta-analysis 1

Safety Profile

Overall safety:

• Excellent safety track record in clinical trials with few major emergent safety concerns after more than 5 years in clinical practice 1, 3
• Superior safety profile compared to conventional immunosuppressive drugs like cyclosporine or methotrexate 5

Most common adverse events:

• Ocular complications (most prevalent): Conjunctivitis occurs in 6-15% in clinical trials but up to 26.1% in real-world data 1
• Dry eyes reported frequently in clinical practice 1
• Nasopharyngitis (28% vs 26% placebo) 6
• Injection site reactions 6, 7
• Head and neck dermatitis (19.5% in real-world data) 8
• Skin infections occur less frequently than placebo 7, 5

Important safety considerations:

• No increased risk of serious infections compared to placebo 7
• Mild-to-moderate adverse events that rarely require discontinuation 8, 7
• Only 4.2% of patients discontinue due to ocular complications 1

Management of Ocular Adverse Events

Monitoring and initial management:

• Advise patients to report new onset or worsening eye symptoms 2
• Regular follow-up to assess for ocular symptoms 3

Treatment algorithm for dupilumab-related ocular surface disorders (DROSD):

• Mild symptoms: Preservative-free ocular lubricants and topical antihistamine eyedrops 3
• Moderate symptoms: Add warm compresses for blepharitis/meibomian gland dysfunction; consider tacrolimus ointment to lid margins (adults and children >7 years) 1
• Severe symptoms: Refer to ophthalmology within 4 weeks; short-term topical corticosteroids (dexamethasone 0.1%, prednisolone 0.5%, or hydrocortisone 0.335%) with early introduction of corticosteroid-sparing agents like ciclosporin drops 1

Indications for dupilumab withdrawal:

• Progressive loss of visual acuity unresponsive to treatment (strong recommendation) 1
• Progressive conjunctival cicatrization or scarring (conditional recommendation) 1
• Significant quality of life loss from inadequately controlled DROSD 1
• Requirement for prolonged ocular topical corticosteroid therapy (>8 weeks) with risk of serious adverse effects 1

Dosing and Administration

Standard dosing by age:

• Adults: 600 mg initial dose (two 300 mg injections at different sites), then 300 mg every 2 weeks 2
• Administered subcutaneously into thigh, abdomen (avoiding 2 inches around navel), or upper arm (if caregiver administers) 2
• Rotate injection sites with each administration 2

Administration considerations:

• Pre-filled pen for patients ≥2 years 2
• Pre-filled syringe for patients ≥6 months 2
• Patients ≥12 years may self-inject under adult supervision 2
• Children 6 months to <12 years require caregiver administration 2

Special Populations and Contraindications

Contraindications:

• Known hypersensitivity to dupilumab or any ingredient 2

Precautions:

• Avoid live vaccines immediately before and during treatment 2
• Monitor for eosinophilic conditions (eosinophilic pneumonia, eosinophilic granulomatosis with polyangiitis) 2
• Screen for and treat helminth infections before initiating therapy 2
• Not for acute symptom relief 2

Co-morbid asthma:

• Patients should not adjust or stop asthma treatments without provider consultation 2
• Do not use for acute bronchospasm or status asthmaticus 2

Pregnancy:

• Pregnancy exposure registry available (1-877-311-8972) 2
• Unknown whether dupilumab harms unborn baby 2

Clinical Pearls and Common Pitfalls

Key advantages:

• Can be used concomitantly with topical agents for maintenance, rescue, or flare treatment 1
• No requirement for routine laboratory monitoring unlike conventional immunosuppressants 5
• Reduces systemic inflammation associated with atopic dermatitis 7

Common pitfalls to avoid:

• Failing to counsel patients about ocular adverse events before initiation 1
• Not establishing ophthalmology referral pathway for DROSD management 1
• Discontinuing therapy prematurely for mild ocular symptoms that respond to conservative management 8
• Using in patients with active helminth infections without prior treatment 2

When to consider alternatives:

• Patients with pre-existing severe ocular surface disease 1
• Patients requiring faster onset of action (JAK inhibitors may be more appropriate) 1
• Patients with DROSD refractory to ophthalmologic management should be switched to alternative systemic therapy like JAK inhibitors 9