What are the next treatment options for a patient with atopic dermatitis who has failed treatment with Dupixent (dupilumab)?

Next Treatment Options After Dupilumab Failure in Atopic Dermatitis

For patients with atopic dermatitis who have failed treatment with dupilumab, Janus kinase (JAK) inhibitors such as upadacitinib or abrocitinib are strongly recommended as the next line of therapy due to their proven efficacy and different mechanism of action. 1

Understanding Treatment Failure with Dupilumab

Before switching therapies, it's important to determine the nature of the dupilumab failure:

• Inadequate efficacy: Patient doesn't achieve adequate control of symptoms
• Adverse effects: Most commonly dupilumab-related ocular surface disorders (DROSD)
• Loss of response: Initial improvement followed by worsening

Dupilumab-Related Ocular Surface Disorders (DROSD)

If treatment failure is due to ocular complications:

• Assess severity of DROSD using standardized grading
• For mild-moderate DROSD: Consider continuing dupilumab while treating the ocular condition with:
  • Ocular lubricants
  • Topical antihistamines
  • Tacrolimus ointment for lid margins
  • Short-term topical corticosteroid drops for moderate-severe cases 1
• For severe, persistent DROSD requiring >8 weeks of topical corticosteroids or causing significant quality of life impairment, discontinuation of dupilumab is recommended 1

Next-Line Treatment Options

1. JAK Inhibitors (First Choice)

JAK inhibitors are strongly recommended for adults with moderate-to-severe AD who have failed dupilumab 1:

• Upadacitinib: FDA-approved for patients who have failed other systemic therapies including biologics

  • Dosing: 15-30 mg once daily
  • Achieves EASI-75 in approximately 77% of patients with moderate-to-severe AD 1

• Abrocitinib: FDA-approved for patients who have failed other systemic therapies including biologics

  • Dosing: 100-200 mg once daily
  • Strong recommendation based on moderate certainty of evidence 1

Monitoring requirements for JAK inhibitors:

• Complete blood count
• Liver enzymes
• Lipid profile
• Screen for tuberculosis before initiation

2. Alternative Biologics

• Tralokinumab: Anti-IL-13 monoclonal antibody

  • Strong recommendation for adults with moderate-to-severe AD 1
  • May have lower incidence of ocular complications compared to dupilumab 1

• Lebrikizumab: Anti-IL-13 monoclonal antibody (emerging therapy)

  • Similar mechanism to tralokinumab but not yet FDA-approved
  • Note: May still have risk of ocular complications as it targets IL-13 pathway 1

3. Conventional Systemic Therapies

If biologics and JAK inhibitors are not options:

• Cyclosporine: 2.5-5 mg/kg/day

  • Onset of action: 2-4 weeks
  • Requires blood pressure and renal function monitoring

• Methotrexate: 10-15 mg/m²/week

  • Onset of action: 8-12 weeks
  • Requires liver function and complete blood count monitoring

• Azathioprine: 1-2.5 mg/kg/day

  • Onset of action: 8-12 weeks
  • Consider TPMT/NUDT15 testing before initiation 1

4. Phototherapy

• Conditionally recommended for adults with AD 1
• Narrow-band UVB is most commonly used
• Requires specialized equipment and regular visits

Special Considerations

• Cancer history: Dupilumab has shown safety in patients with advanced cancer, while traditional immunosuppressants pose higher risks 2
• Ocular comorbidities: Consider tralokinumab if patient had DROSD with dupilumab 1
• Age considerations: Upadacitinib is approved for patients ≥12 years, while other options may have different age restrictions 1

Treatment Algorithm

1. Confirm true treatment failure with dupilumab (inadequate response after 16 weeks or intolerable adverse effects)
2. Rule out confounding factors (infection, contact dermatitis, medication non-adherence)
3. Select next therapy based on failure reason:
   • If failure due to lack of efficacy: JAK inhibitor (upadacitinib or abrocitinib)
   • If failure due to DROSD: Try managing DROSD first; if unsuccessful, switch to tralokinumab or JAK inhibitor
   • If contraindications to JAK inhibitors: Consider tralokinumab or conventional immunosuppressants

Common Pitfalls to Avoid

• Switching therapy too early before dupilumab has had adequate time to work (16 weeks minimum)
• Failing to address ocular complications that might be manageable without discontinuing dupilumab
• Not considering combination approaches (e.g., adding methotrexate to dupilumab) before switching completely
• Overlooking the need for continued basic therapy (moisturizers, topical anti-inflammatory agents) when transitioning between systemic agents