What are other biological treatments, besides dupilumab (Dupixent), that have received FDA (Food and Drug Administration) approval for the treatment of atopic dermatitis, and what emerging therapies are available for the same indication?

FDA-Approved Biological Treatments for Atopic Dermatitis and Emerging Therapies

Besides dupilumab, tralokinumab is the only other FDA-approved biological treatment for moderate-to-severe atopic dermatitis in adults, while JAK inhibitors like upadacitinib represent emerging therapeutic options for patients who fail first-line biologics. 1, 2

FDA-Approved Biologics for Atopic Dermatitis

Tralokinumab

• Mechanism of action: Human IgG4 monoclonal antibody that specifically targets and neutralizes interleukin-13 (IL-13) 1, 3
• FDA approval status: Approved for adults with moderate-to-severe atopic dermatitis 3, 2
• Dosing regimen: 600 mg subcutaneous injection at initiation followed by 300 mg every 2 weeks 1
• Efficacy:
  • Significantly improves signs, symptoms, and quality of life in moderate-to-severe AD 1, 4
  • Real-world data shows 58% of patients achieve EASI-75 by week 16 4
  • Somewhat less effective than dupilumab in network meta-analyses 1
• Safety profile:
  • Excellent safety record in clinical trials with no major safety concerns identified 1
  • Comparable safety profile to placebo 4

Dupilumab

• Mechanism of action: Monoclonal antibody targeting the interleukin-4 receptor α, blocking both IL-4 and IL-13 signaling 1, 5
• FDA approval status: First FDA-approved targeted systemic treatment for AD, approved for patients as young as 6 months old 1, 2
• Efficacy:
  • Established efficacy in large RCTs, including a 52-week randomized trial 1
  • Meta-analyses show significant improvements in EASI, SCORAD, and pruritus scores 5
• Safety profile: Excellent safety record in clinical trials and few major safety concerns after more than 5 years in clinical practice 1

Emerging Therapies for Atopic Dermatitis

JAK Inhibitors

• Upadacitinib (Rinvoq):
  • Mechanism: Selective JAK-1 inhibitor 6
  • FDA approval status: FDA-approved for moderate-to-severe AD 6
  • Place in therapy: Second-line systemic therapy after failure of other systemic therapies (including biologics) or when those therapies are inadvisable 6
  • Efficacy: Higher efficacy than dupilumab at standard dosing 1
  • Safety concerns: Carries important warnings for serious infections, increased mortality risk, malignancy, major adverse cardiovascular events, and thrombosis 6

Treatment Algorithm for Atopic Dermatitis

1. First-line therapies:

   • Topical treatments and emollients 6

2. Second-line therapies (when topicals fail):

   • Biologics (dupilumab preferred as first-line systemic agent by guideline workgroup members) 1, 6
   • Phototherapy (conditional recommendation, particularly narrowband UVB) 1

3. Third-line therapies (after failure of biologics):

   • JAK inhibitors (upadacitinib) 6
   • Traditional immunosuppressants 6

Clinical Considerations

• Biologic selection: Dupilumab is generally favored as first-line systemic therapy by experts due to its established efficacy and excellent safety profile 1
• Treatment response: Response rates to tralokinumab may be higher in biologic-naive patients (67% EASI-75) compared to those previously treated with biologics or JAK inhibitors (41% EASI-75) 4
• Combination therapy: Topical agents can be used concurrently with systemic agents for maintenance, rescue, or treatment of flares 1

Important Caveats

• There are no head-to-head studies directly comparing tralokinumab against other systemic therapies 1
• JAK inhibitors should not be used as first-line therapy due to their safety profile 6
• When selecting therapy, consider patient factors such as age, comorbidities, and previous treatment responses
• Regular monitoring for adverse effects is essential, particularly with JAK inhibitors