Atopic Dermatitis: OX40, IL-31, Treg Therapy, and the JAK Head-to-Head Era
Emma Guttman-Yassky, MD, PhD, delivered a sweeping update on advances in atopic dermatitis (AD) during her Masterclasses in Dermatology session, “Atopic Dermatitis Treatment Update,” tracing how translational immunology reshaped the treatment landscape.
“Both successes and failures have helped to frame pathogenic concepts and therapeutic directions,” she noted, reflecting on the shift from broad immunosuppressants, such as cyclosporine, methotrexate, and azathioprine, to targeted biologics and small molecules. Traditional agents are effective but carry infection and safety risks, underscoring the need for precision therapy.
Dupilumab, targeting IL-4Rα and blocking IL-4/IL-13 signaling, remains foundational. In pooled SOLO 1 and 2 studies, Eczema Area and Severity Index (EASI)-75 responses at week 16 approached 47% to 50% vs placebo, with durable safety through 172 weeks. Conjunctivitis rates in pediatric populations were comparable to adults.
Selective IL-13 inhibition has expanded options. In ADvocate 1 and 2, lebrikizumab achieved significant EASI-75 and Validated Investigator Global Assessment (vIGA)-AD 0/1 responses at week 16, with maintenance through week 52. Nemolizumab, targeting IL-31, demonstrated statistically significant improvements in pruritus Numeric Rating Scale and lesional severity in ARCADIA 1 and 2, particularly among patients with severe baseline itch. “Highly statistically significant endpoints with nemolizumab” were observed across trials.
Targeting IL-22 also shows promise. Temtokibart, an IL-22 receptor antagonist, achieved significant EASI improvement at week 16 in phase 2b data, with maintenance up to week 32 and a favorable safety profile.
The OX40/OX40L pathway represents a major innovation. Rocatinlimab (anti-OX40) met co-primary endpoints (EASI-75 and vIGA-AD 0/1) in the phase 3 ROCKET-IGNITE trial, with durable EASI-75 responses even after discontinuation. Amlitelimab (anti-OX40L) met all primary and key secondary endpoints in COAST-1.
A novel immunoregulatory approach emerged with rezpegaldesleukin, a selective regulatory T-cell–inducing IL-2 conjugate. In the phase 2b REZOLVE-AD trial, all dose arms met the primary endpoint of mean percent EASI change at week 16 (P<0.001). Higher-dose arms showed clear separation for EASI-75 and EASI-90. Injection site reactions occurred in 70% of patients, mostly early and localized.
Oral JAK inhibitors continue to redefine expectations. In head-to-head data, upadacitinib achieved higher EASI-90 and EASI-100 responses than dupilumab at week 16. Abrocitinib maintained or increased EASI-100 responses through 96 weeks, although herpes zoster and certain safety signals were more frequent in older or smoking populations.
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Reference
Guttman E. Atopic dermatitis treatment update. Presented at: Masterclasses in Dermatology; February 19–22, 2026; Sarasota, FL.
