Biologics in Atopic Dermatitis
Primary Recommendation
For adults with moderate-to-severe atopic dermatitis inadequately controlled by topical therapies, dupilumab is the first-line systemic therapy with a strong recommendation based on moderate-certainty evidence. 1
Treatment Algorithm for Systemic Therapy Selection
First-Line Biologic Therapy
Dupilumab receives the strongest endorsement from the American Academy of Dermatology, with all guideline workgroup members favoring it over other systemic agents for moderate-to-severe atopic dermatitis. 2, 3
- Dosing: 600 mg subcutaneous loading dose, then 300 mg every 2 weeks 2
- Expected efficacy: 63-64% achieve EASI 75 at 16 weeks when combined with topical corticosteroids 2
- Mechanism: Fully human IgG4 monoclonal antibody blocking IL-4 receptor α subunit, inhibiting both IL-4 and IL-13 signaling 2
Alternative Biologic Options (Strong Recommendations)
Tralokinumab is an alternative first-line biologic with a strong recommendation for adults with moderate-to-severe atopic dermatitis. 1
- Approved for patients ≥18 years old 4
- Targets IL-13 specifically 5
- Comparable efficacy and safety profile to dupilumab 4
Patient Selection Criteria
Candidates for Biologic Therapy
Initiate biologics when patients meet these criteria:
- Disease severity: Moderate-to-severe atopic dermatitis affecting multiple body areas 2, 3
- Treatment failure: Inadequate response to optimized topical prescription therapies 1, 6
- Sensitive area involvement: Face, ears, or other high-impact locations 2, 3
- Quality of life impairment: Substantial impact despite topical management 2, 3
FDA Approval Considerations
- Dupilumab: Approved for patients as young as 6 months old 6, 4
- Tralokinumab: Approved for patients ≥18 years old 4
Safety Profile and Adverse Event Management
Overall Safety
Dupilumab demonstrates an excellent safety track record with few major emergent safety concerns after more than 5 years in clinical practice. 2, 3
Ocular Adverse Events (Most Common)
Conjunctivitis is the most prevalent adverse event, occurring in 6-15% of patients in clinical trials and up to 26.1% in real-world data. 2, 7
Management algorithm for ocular complications:
- Mild symptoms: Preservative-free ocular lubricants and topical antihistamine eyedrops 2, 3
- Moderate symptoms: Continue dupilumab while treating ocular symptoms 2
- Severe symptoms: Refer to ophthalmology 2
- Only 4.2% discontinue dupilumab due to ocular complications 2
Indications for dupilumab withdrawal:
- Progressive loss of visual acuity 2
- Progressive conjunctival cicatrization 2
- Significant quality of life loss from ocular symptoms 2
- Requirement for prolonged ocular topical corticosteroid therapy 2
Other Notable Adverse Events
New-onset psoriasis has been reported with dupilumab use—advise patients to report new psoriatic symptoms. 6, 8
Eosinophilic conditions (eosinophilic pneumonia, eosinophilic granulomatosis with polyangiitis) require patient notification to healthcare provider if clinical features develop. 6
Previously unreported adverse events in real-world data include blood eosinophilia, rosacea-like skin lesions, and weight gain, though mechanistic association requires clarification. 7
Critical Clinical Pearls
Concomitant Therapy
Always use dupilumab with topical agents for maintenance, rescue, or flare treatment—do not use as monotherapy without topical support. 2, 3
Pre-Treatment Counseling
Counsel all patients about ocular adverse events before initiating dupilumab and establish an ophthalmology referral pathway for management. 2, 3
Monitoring Requirements
Regular follow-up is essential to assess treatment response and monitor for adverse effects, particularly ocular symptoms. 3, 6
Vaccination Considerations
Live vaccines are not recommended immediately prior to or during dupilumab therapy—patients must inform healthcare providers about dupilumab use before vaccination. 6
Alternative Systemic Therapies
JAK Inhibitors (Strong Recommendations)
The following JAK inhibitors also receive strong recommendations for moderate-to-severe atopic dermatitis:
FDA approval caveat: These JAK inhibitors are approved for patients who have failed other systemic therapies (pills or injections, including biologics) or when use of those therapies is inadvisable. 1
Conditional Recommendations
Phototherapy, cyclosporine, methotrexate, azathioprine, and mycophenolate receive conditional recommendations for use in atopic dermatitis. 1
Strong Recommendation Against
Systemic corticosteroids are conditionally recommended against for atopic dermatitis due to substantial risk of serious adverse events and rebound flares upon discontinuation. 1
Management of Inadequate Response
When Dupilumab Fails
If inadequate response to dupilumab occurs:
- Rule out confounding dermatoses before declaring treatment failure 9
- Consider individual goals and quality of life, not just body surface area 9
- Adjust dosing frequency in some circumstances 9
- Add adjuvant therapies: methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, or phototherapy (though safety and efficacy of combinations are not established) 9
- Switch to JAK inhibitor such as upadacitinib if psoriasiform switch occurs 8
Patients Requiring Alternative Therapies
Consider alternatives to dupilumab for: