The prevalence of AD is high, not only in the USA and Europe, but worldwide. An increased understanding of the genetic immune function abnormalities and pathogenesis of underlying AD provides researchers with opportunities to develop more targeted therapies. There is a need for long-term therapies that are safe and effective for chronic atopic dermatitis. Current research and ongoing phase 2 and 3 studies show many promising new agents with increased efficacy and reduced adverse effects, that can be used as monotherapy or as combination oral and topical treatments.

• Clinical treatment options for patient are no longer limited to broad immunosuppressive therapies, as newer more targeted therapies are becoming available.
• AD differs from plague psoriasis over the natural course of the disease spanning many years; disease morphology exhibits change.

• Peripheral monocytes in AD demonstrate elevated phosphodiesterase-4 enzyme activity and decreased cyclic adenosine monophosphate levels.
• PDE inhibition is an effective element in the treatment of AD.
• Difamilast ointment 1% (PDE4B) for the treatment of AD has shown rapid relief of itch with a median time-to-improvement of 5.8 hours, and sustained efficacy to 29 days.

Crisaborole

• Phase 3 studies in children and adolescents with mild to moderate AD [1].
• Crisaborole has demonstrated clinically significant efficacy in two multicenter, double-blind phase 3 studies in achieving primary endpoint of clear or almost clear skin, with a ≥2 grade improvement from baseline measures.
• Reported adverse events (10.2%) included application site pain, and application site infection.

Dupilumab

• Dupilumab shows promise in the treatment of moderate to severe AD at week 16 through inhibition of IL-4 type 1 and 2 receptors [2].
• This demonstrates the role of IL-4 in AD pathogenesis.
• Studies demonstrate efficacy in change in Eczema Area and Severity Index (EASI) score and itch measures from baseline.
• The safety profile demonstrated a risk of conjunctivitis (7-12%) and injection site reactions (10-20%).
• Combination dupilumab and topical corticosteroids.
• Dupilumab can be safely administered in combination with standard topical corticosteroids for the long-term management of moderate-to-severe AD (1 year); clinical studies demonstrate that the addition of topical steroids improves patient outcomes versus administration of dupilumab as monotherapy.

Tralokinumab

• Tralokinumab targets the role of IL-13 in the pathogenesis of AD and has been proven safe and effective in reducing symptoms in phase 2b studies [3].
• Patients with moderate-to-severe AD symptoms demonstrated a clinically significant improvement in EASI score and IGA response over baseline.
• The most frequent AE reported was upper respiratory infection [3].

Nemolizumab

• Nemolizumab targets IL-31 in the treatment of moderate-to-severe AD [4].
• It is indicated for patients who have not achieved adequate control with topical corticosteroids.
• Phase 2, randomized, placebo-controlled, double blind studies demonstrate long-term efficacy in EASI score improvement when injected subcutaneously every 4 weeks or every 8 weeks.
• Nemolizumab overall was well tolerated.

Tradipitant

• The symptomatic role of itch in the EASI score is significant.
• Tradipitant NK 1R antagonist is a new and emerging therapy for AD shown to reduce symptoms of itch and overall disease severity in phase 2 studies [5].

Several new and emerging treatments reflect the trend toward targeted therapies, including JAK inhibitors for the treatment of AD, both as oral and topical treatments [6-9].

Oral JAK Inhibitors

• Oral upadacitinib : inhibits JAK1.
• Oral PF-04965842 : inhibits JAK1.
• Oral baricitinib : inhibits JAK1, JAK2.
• Oral ASN002 : inhibits JAK/SYK, including TYK2.
• Oral tofacitinib : inhibits JAK3, JAK1, JAK2.

Topical JAK Inhibitors

• Topical tofacitinib : inhibits JAK3, JAK1, JAK2.
• Topical ruxolitinib : inhibits JAK1, JAK2.
• Topical delgocitinib/JTE-052 : inhibits JAK1, 2, 3 and TIK2.

JAK inhibitors generally demonstrate favorable safety profiles and efficacy in achieving primary outcomes.