For Atopic Dermatitis, "The Treatment Drought is Over," Says Expert Dermatologist Emma Guttman, MD, PhD

Atopic dermatitis (AD), the most prevalent inflammatory skin disorder, affects approximately 7% of adults and 15% of children in the US. Notably, 20% to 30% of affected individuals have moderate-to severe disease, according to internationally recognized dermatologist Emma Guttman, MD PhD, the Waldman Professor of Dermatology and Immunology and health system chair of the Department of Dermatology at the Icahn School of Medicine at Mount Sinai in New York, NY.

Emma Guttman, MD, PhD

AD has long posed a challenge in terms of sustained disease control, creating a large unmet need for more effective therapies, Guttman explained. During a “Hot Topics” session on the final day of the 2025 American Academy of Dermatology (AAD) conference in Orlando, FL, however, she offered a topline look at the therapeutic landscape that has experienced an unprecedented transformation in just the past 5 years, declaring as she began her presentation that “the therapeutic drought is over.”

More than a skin disorder. AD has traditionally been viewed as a cutaneous disorder, however, Guttman pointed to a growing body of evidence that supports the systemic nature of AD. Studies have demonstrated its associations with cardiovascular disease and other systemic comorbidities, Pavel et al. (2020) and Silverberg et al. (2015), underscoring the importance of targeted systemic treatments for patients with moderate-to-severe disease affecting 10% or more of body surface area (BSA).

Expanding pipeline: Biologics plus so much more. Guttman reviewed the expanding toolbox of targeted therapies, including IL-13 inhibitors tralokinumab and lebrikizumab—both now FDA-approved—as well as the growing number of novel agents targeting interleukin receptors, Janus kinase (JAK) signaling, and, most recently, OX40/OX40L pathways. While traditional immunosuppressants, including cyclosporine A, methotrexate, and azathioprine have all proven effective, she reminded the audience that they are associated with a significant risk of infection. The roster of newer agents provide targeted immune modulation with safety profiles that are considered far more favorable, Guttman said.

Dupilumab: The first and still leading. Dupilumab, the first FDA-approved biologic for AD, continues to set the standard for efficacy and safety. The fully humanized IgG4 monoclonal antibody inhibits interleukin (IL)-4 and -13 signaling, the key cytokines involved in type 2 inflammatory diseases. Long-term data now extend up to 172 weeks, showing sustained disease control with very low risk for treatment emergent adverse events. Dupilumab also is approved to treat moderate to severe disease in individuals aged 6 months and older. Notably, rates of conjunctivitis—a concern in earlier studies—appear comparable between adult and pediatric populations, Guttman pointed out. In a pooled analysis of clinical trials of dupilumab, the treatment trended for lower rates of cutaneous infections.

Emerging Agents in AD Management

• Lebrikizumab: In phase 3 trials (ADvocate 1 and 2), the IL-13 inhibitor demonstrated significant improvements in EASI-75 and Investigator’s Global Assessment (IGA) responses, with lower conjunctivitis rates than those seen with dupilumab.
• Tralokinumab: In the ECZTEND open label extension trial (participants from ECZTRA 1 , 2, and 5 trials) tralokinumab demonstrated high levels of efficacy with maintenance of effect at 56 weeks and at 2 years across all studies.
• JAK Inhibitors (upadacitinib, abrocitinib): These oral agents exhibit rapid onset of action and robust efficacy, including high EASI-90/100 responses. However, safety concerns—particularly in older adults and those with cardiovascular risk factors—make careful patient selection essential, Guttman commented.
• Nemolizumab: Targeting IL-31, this agent has shown promising results in pruritus reduction and skin lesion improvement.
• OX40/OX40L Inhibitors (rocatinlimab, amlitelimab): These agents, which modulate T-cell activation, are emerging as potential long-term disease-modifying therapies.

Guttman championed a precision-medicine approach when selecting treatments for AD that includes consideration of factors including patient age, comorbidities (eg, asthma, alopecia areata), and safety profiles of the agents being considered. For extensive disease, early initiation of systemic therapy is recommended, while limited disease may be managed effectively with advanced topical therapies such as the topical JAK1/2 inhibitor ruxolitinib or a PDE4 inhibitor like roflumilast.

Guttman concluded with the recognition that the expanding therapeutic armamentarium for AD points to a future of disease management that is increasingly personalized and targeted. Data shared at the 2025 AAD conference, which encompassed all the treatments in Guttman's discussion, come at a point when clinicians can already provide patients with AD both options and alternatives, matching treatment more precisely to their needs and preferences. The extended drought is indeed over and has given way to an era of refined immunomodulation.