What are the treatment options for a patient with moderate to severe eczema, possibly with a history of allergies or asthma, who has failed topical therapies?

Biological Therapy for Moderate to Severe Eczema

For patients with moderate to severe eczema who have failed topical therapies, dupilumab is the first-line biologic with the strongest evidence for efficacy and safety, showing significant improvements in disease severity, pruritus, and quality of life. 1, 2

First-Line Biologic: Dupilumab

Dupilumab should be initiated as the preferred biologic agent for moderate-to-severe atopic dermatitis inadequately controlled by topical therapies. 1

Mechanism and Approval

• Dupilumab is a fully human monoclonal antibody that blocks the IL-4 receptor alpha subunit, thereby inhibiting both IL-4 and IL-13 signaling pathways central to type 2 inflammation in atopic dermatitis 2
• FDA-approved for patients aged 6 months and older with moderate-to-severe AD whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable 2
• Can be used with or without concomitant topical corticosteroids 2

Dosing and Administration

• Adults: Initial dose of 600 mg (two 300 mg injections at different sites), followed by 300 mg every 2 weeks 2
• Administered subcutaneously into the thigh, abdomen (avoiding 2 inches around navel), or upper arm 2
• Patients aged 12 years and older may self-inject under adult supervision; younger children require caregiver administration 2

Efficacy Data

• In pivotal trials (SOLO 1, SOLO 2, CHRONOS), 36-38% of patients achieved clear or almost clear skin (IGA 0/1) at week 16 versus 9-10% with placebo 2
• 44-51% achieved EASI-75 (75% improvement in disease severity) as monotherapy versus 12-15% with placebo 2
• When combined with topical corticosteroids, 69% achieved EASI-75 versus 23% with placebo 2
• 36-41% experienced clinically meaningful itch reduction (≥4-point improvement on pruritus scale) versus 10-12% with placebo 2

Safety Profile

• Generally well-tolerated with low rates of serious adverse events and treatment discontinuations 3
• Most common adverse reactions: conjunctivitis (reported in clinical trials), injection-site reactions, and oral herpes 2, 3
• Approximately 5-16% of patients develop anti-drug antibodies, with only 2-3% showing persistent responses 2
• Two cases of serum sickness or serum sickness-like reactions have been reported in patients with high-titer antibodies 2

Alternative Biologic Options

If dupilumab is contraindicated, ineffective, or not tolerated, tralokinumab represents the next biologic option. 1, 4

• Tralokinumab is an IL-13 monoclonal antibody approved in Europe (2021) for moderate-to-severe AD in adults 4
• The 2024 AAD guidelines make strong recommendations for tralokinumab as an alternative biologic 1

JAK Inhibitors as Systemic Alternatives

The 2024 AAD guidelines make strong recommendations for three JAK inhibitors: abrocitinib, baricitinib, and upadacitinib. 1

• These oral small-molecule therapies inhibit Janus kinases involved in inflammatory signaling pathways 4
• Offer an alternative route of administration (oral versus injectable) for patients who prefer or require non-biologic systemic therapy 1

Traditional Systemic Immunosuppressants

When biologics and JAK inhibitors are not accessible or appropriate, traditional immunosuppressants may be considered, though with conditional recommendations due to safety concerns. 1

Cyclosporine

• The 2024 AAD guidelines provide conditional recommendations for cyclosporine 1
• The only traditional immunosuppressant with regulatory approval for severe AD in some jurisdictions 4
• Requires monitoring: CBC, complete metabolic panel 1

Methotrexate

• Conditional recommendation from 2024 AAD guidelines 1
• Typical dosing: 7.5-25 mg orally once weekly 1
• Requires monitoring: CBC, complete metabolic panel 1
• Key adverse effects: hepatotoxicity, bone marrow suppression, teratogenicity 1

Azathioprine

• Conditional recommendation from 2024 AAD guidelines 1
• Typical dosing: 1-3 mg/kg daily 1
• Requires monitoring: CBC, complete metabolic panel, TPMT testing before initiation 1

Mycophenolate

• Conditional recommendation from 2024 AAD guidelines 1
• Typical dosing: 1.0-1.5 g orally twice daily; pediatric 30-50 mg/kg daily 1
• Requires monitoring: CBC, complete metabolic panel 1

Phototherapy Considerations

Phototherapy should be considered before traditional systemic immunosuppressants if accessible and practical. 1

• Narrowband UVB (311-313 nm) shows the greatest efficacy among phototherapy modalities 1
• The 2024 AAD guidelines provide conditional recommendations for phototherapy 1
• Typical regimen requires 2-3 treatments per week for 10-14 weeks, which limits accessibility for many patients 1
• Long-term skin cancer risk, particularly with PUVA, must be weighed against benefits 1
• Not recommended for children younger than 12 years 1

What NOT to Use

Oral corticosteroids should be avoided for long-term management of moderate-to-severe AD. 1

• The 2024 AAD guidelines make conditional recommendations against the use of systemic corticosteroids 1
• Short-term use (<7 days) may be considered only for severe acute exacerbations, but rebound flares are common upon discontinuation 1
• Recent evidence shows short-term OCS use is associated with increased risk of severe adverse events even in brief courses 1

Treatment Algorithm

Step 1: Optimize Topical Therapy First

• Ensure adequate trial of medium-to-high potency topical corticosteroids with proper application technique 1
• Consider topical calcineurin inhibitors (tacrolimus, pimecrolimus) for maintenance 1
• Maximize emollient use and trigger avoidance 1

Step 2: Address Secondary Factors

• Treat bacterial superinfection (usually S. aureus) with systemic antibiotics before initiating systemic therapy 1
• Consider patch testing if allergic contact dermatitis is suspected (facial/eyelid predominance, unusual distribution patterns) 1
• Evaluate for viral infections, particularly eczema herpeticum, which requires prompt antiviral therapy 1

Step 3: Initiate Dupilumab

• Start dupilumab 600 mg loading dose, then 300 mg every 2 weeks 2
• Can be used with or without continued topical corticosteroids 2
• Assess response at 16 weeks; most patients show significant improvement by this timepoint 2

Step 4: If Dupilumab Fails or Is Contraindicated

• Consider tralokinumab (alternative IL-13 inhibitor) 1, 4
• Consider JAK inhibitors (abrocitinib, baricitinib, or upadacitinib) 1
• Phototherapy (narrowband UVB) if accessible 1

Step 5: Traditional Immunosuppressants as Last Resort

• Cyclosporine, methotrexate, azathioprine, or mycophenolate with appropriate monitoring 1
• These carry higher safety concerns and require regular laboratory monitoring 1

Critical Pitfalls to Avoid

Do not continue ineffective treatments indefinitely—if no response is seen after an adequate trial period (typically 12-16 weeks for biologics, 8-12 weeks for traditional immunosuppressants), switch to an alternative agent 1

Do not initiate systemic therapy without first addressing bacterial or viral superinfection, as persistent infection impairs treatment response 1

Do not use oral corticosteroids as maintenance therapy due to rebound flares and adverse effects; reserve only for short-term (<7 days) management of severe acute exacerbations 1

Do not forget to complete age-appropriate vaccinations before starting dupilumab, as live vaccines are not recommended during treatment 2

Monitor for conjunctivitis in dupilumab-treated patients and advise them to report new or worsening eye symptoms promptly 2