Exploring Newer Nonsteroidal Topical Treatments for Atopic Dermatitis: JAK Inhibitors and AhR Agonists

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Topical Janus kinase (JAK) Inhibitors in Atopic Dermatitis Management

Agents Discussed: Ruxolitinib (Opzelura), Tapinarof

Ruxolitinib (Topical JAK1/JAK2 Inhibitor)

• Indication and Approval:
  • Approved for the treatment of atopic dermatitis in patients aged 12 years and older
  • Maximum recommended body surface area (BSA) coverage is 20%, per FDA labeling
• Efficacy Data:
  • In the TRuE-AD1 study, 54% of patients using 1.5% ruxolitinib cream achieved an IGA score of 0 or 1 (clear or almost clear skin)
  • Demonstrated superiority to medium-potency topical steroids (triamcinolone 0.1% ointment) in a phase 2 head-to-head study, with greater efficacy in reducing inflammation and pruritus
• Tolerability and Safety:
  • Common adverse events include nasopharyngitis, upper respiratory tract infections, and headache.
  • Notable for lack of local adverse effects often associated with corticosteroids, such as atrophy, striae, and hypopigmentation—a key benefit in treating sensitive areas (eg, face, genitals, intertriginous zones)
• Black Box Warning:
  • Important to contextualize: The black box warning stems from a phase 4 safety trial of oral JAK inhibitors (tofacitinib) in older patients with rheumatoid arthritis, where increased risks of thromboembolism and cardiovascular events were observed
  • These findings do not directly apply to topical formulations, which have minimal systemic absorption, yet the warning remains due to the class effect
  • Physicians should educate patients and caregivers about this distinction to mitigate concerns

Tapinarof (Topical Aryl Hydrocarbon Receptor [Ahr] Modulator)

• Study Reference: ADORING Clinical Trial:
  • Included 813 subjects, 18 years or younger, with an average BSA involvement of approximately 17%
• Efficacy:
  • After 8 weeks of treatment, approximately 45% to 46% of participants achieved an IGA score of 0 or 1.
• Adverse Events:
  • Most common: Folliculitis, headache, and nasopharyngitis
  • Folliculitis appears to be the most prominent adverse event in clinical practice
    • Management includes standard treatments such as topical clindamycin or benzoyl peroxide washes
• Clinical Considerations:
  • Generally, well tolerated
  • A nonsteroidal alternative beneficial for patients seeking long-term topical treatment without corticosteroid-associated risks

Clinical Takeaways

• Topical JAK inhibitors like ruxolitinib offer effective nonsteroidal alternatives with notable benefits in itch relief, inflammation reduction, and safety profile, especially in sensitive or chronic-use areas
• Physicians should educate patients on the context of black box warnings, and tailor therapy based on efficacy, tolerability, and anatomical site of involvement
• Tapinarof presents another promising nonsteroidal option, with mild, manageable adverse effects