Atopic Dermatitis: Dupilumab, JAK Inhibitors, and Emerging Therapies

Dupilumab: The Biologic Standard of Care

Atopic dermatitis management has been transformed by the arrival of biologic and small-molecule therapies that target the underlying type 2 immune dysregulation rather than broadly suppressing the immune system. For the dermatologist, allergist, or primary care physician managing moderate-to-severe AD, the treatment algorithm now extends well beyond topical corticosteroids and calcineurin inhibitors. Understanding how to select among dupilumab, JAK inhibitors, and emerging agents — and when to escalate from topical to systemic therapy — is essential for providing guideline-concordant care.

Dupilumab, an anti-IL-4/IL-13 monoclonal antibody, established the biologic era for atopic dermatitis (AD). The SOLO 1 and SOLO 2 trials demonstrated that dupilumab 300 mg every 2 weeks achieved IGA 0/1 (clear/almost clear) in 36-38% of patients versus 8-10% with placebo at 16 weeks, with EASI-75 response in 44-51%[1]. Long-term data from LIBERTY AD CHRONOS show sustained efficacy through 52 weeks[2] with an acceptable safety profile. The most notable adverse effect is conjunctivitis (8-25% in trials)[3], managed with artificial tears, topical cyclosporine, or tacrolimus eye drops. Dupilumab is FDA-approved for patients aged 6 months and older.

JAK Inhibitors: Oral Options with Rapid Onset

Three oral JAK inhibitors are approved for moderate-to-severe AD: abrocitinib (JAK1-selective), upadacitinib (JAK1-selective), and baricitinib (JAK1/JAK2). In head-to-head trials, upadacitinib 30 mg demonstrated superiority to dupilumab for EASI-75 at week 16 (71% vs 61%, p = 0.006) in the Heads Up trial[4]. Abrocitinib 200 mg showed similar superiority to dupilumab in JADE DARE (EASI-90 at week 4: 29% vs 15%)[5]. JAK inhibitors offer faster onset of action (significant itch reduction within 2-4 days) compared to dupilumab (2-4 weeks). However, the JAK inhibitor safety profile requires consideration of the ORAL Surveillance-related class warnings including cardiovascular risk, VTE, and malignancy, necessitating appropriate screening and monitoring.

Tralokinumab and Emerging Biologics

Tralokinumab, a selective IL-13 inhibitor, achieved IGA 0/1 in 15.8-22.2% and EASI-75 in 25-33.2% as monotherapy (ECZTRA trials)[6], with improved efficacy when combined with topical corticosteroids (EASI-75 of 56%). Lebrikizumab, another IL-13 inhibitor with a longer dosing interval (every 4 weeks after loading), achieved IGA 0/1 in 33.2-38.4% in the ADvocate trials[7]. Nemolizumab (anti-IL-31 receptor) is advancing through Phase 3 trials with particularly strong efficacy for pruritus, the most bothersome AD symptom, achieving a 42.8% improvement in peak pruritus NRS at week 16[8].