What are the injectable treatment options for patients with moderate to severe atopic dermatitis, particularly those with a history of allergies or asthma?

Injectable Treatment Options for Moderate to Severe Atopic Dermatitis

For adults and adolescents ≥12 years with moderate-to-severe atopic dermatitis inadequately controlled by topical therapies, dupilumab is the first-line injectable biologic treatment, with tralokinumab as an alternative option. 1, 2

First-Line Injectable Biologic: Dupilumab

Dupilumab (Dupixent) is the only FDA-approved biologic specifically indicated for moderate-to-severe atopic dermatitis and should be the primary injectable treatment choice. 1, 3

Mechanism and Efficacy

• Dupilumab is a fully human IgG4 monoclonal antibody that blocks IL-4 receptor α subunit, inhibiting both IL-4 and IL-13 signaling pathways central to atopic dermatitis pathophysiology 3, 4
• Phase III trials demonstrated significant improvements in disease severity scores (SCORAD, EASI, IGA), pruritus, sleep disturbance, anxiety, depression, and quality of life compared to placebo 3
• Benefits are maintained during long-term treatment up to 1 year, making it suitable for chronic management 3

Dosing Regimens

Adults:

• Loading dose: 600 mg subcutaneous (two 300 mg injections)
• Maintenance: 300 mg every 2 weeks 2
• For patients <100 kg achieving clear/almost clear skin after 16 weeks, consider reducing to 300 mg every 4 weeks 2

Adolescents 12-17 years:

• Loading dose: 300 mg subcutaneous (two 150 mg injections)
• Maintenance: 150 mg every 2 weeks 2

Safety Profile and Adverse Events

• Generally well-tolerated with low rates of serious adverse events and treatment discontinuations 3
• Most common side effects: conjunctivitis (15.6%), injection-site reactions, head and neck dermatitis (19.5%), oral herpes, skin dryness and peeling (10.9%) 3, 5
• Critical advantage: Skin infections occur LESS frequently compared to placebo, unlike traditional immunosuppressants 4
• Most adverse events are mild and do not require discontinuation 5, 6

Managing Dupilumab-Related Adverse Events

For conjunctivitis (most common concern):

• Continue dupilumab while initiating treatment for conjunctivitis 6
• Early ophthalmology referral if symptoms persist or worsen 6

For head and neck dermatitis:

• This paradoxical reaction occurs in approximately 20% of patients 5
• Can be managed with topical corticosteroids while continuing dupilumab 6

For inadequate response:

• Rule out confounding dermatoses before declaring treatment failure 6
• Consider adding adjuvant therapies: methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, or phototherapy (though safety/efficacy data for combinations are limited) 6

Second-Line Injectable Biologic: Tralokinumab

Tralokinumab (Adbry) is an IL-13 antagonist approved for moderate-to-severe atopic dermatitis in adults and adolescents ≥12 years when topical therapies are inadequate or not advisable. 2

Dosing

Adults:

• Loading dose: 600 mg subcutaneous (four 150 mg injections or two 300 mg injections)
• Maintenance: 300 mg every 2 weeks 2

Adolescents ≥12 years:

• Loading dose: 300 mg subcutaneous (two 150 mg injections)
• Maintenance: 150 mg every 2 weeks 2

Special Considerations for Patients with Allergies/Asthma

Dupilumab offers particular advantages for atopic dermatitis patients with comorbid allergic conditions:

• The IL-4/IL-13 blockade addresses multiple disease mechanisms including IgE class switching and TH2 differentiation, which are relevant to allergic comorbidities 4
• Dupilumab is also FDA-approved for asthma and chronic rhinosinusitis with nasal polyposis, potentially treating multiple atopic conditions simultaneously 3

Pre-Treatment Requirements

Complete all age-appropriate vaccinations before initiating injectable biologics, as these medications may theoretically affect vaccine response. 2

Concomitant Therapy Approach

• Injectable biologics can be used with or without topical corticosteroids 2
• Topical calcineurin inhibitors should be reserved for problem areas only (face, neck, intertriginous, genital areas) 2
• This flexibility allows for individualized treatment intensity based on response 2

Traditional Systemic Immunosuppressants (Non-Injectable)

While the question focuses on injectables, it's important to note that traditional oral immunosuppressants (cyclosporine, azathioprine, methotrexate, mycophenolate mofetil) remain options but are considered experimental with inferior safety profiles compared to dupilumab. 7

• These agents have significant toxicity concerns and require intensive monitoring 7
• Dupilumab's superior safety profile makes it the preferred systemic option when injectable therapy is acceptable 3, 4

Critical Pitfalls to Avoid

• Do not use systemic corticosteroids for maintenance therapy—they should only be used for short-term crisis management due to rebound flares upon discontinuation 7
• Do not declare treatment failure prematurely—assess response at 16 weeks and consider patient-reported quality of life outcomes, not just body surface area 6
• Do not discontinue dupilumab for mild adverse events—most can be managed with adjunctive treatments while continuing therapy 6