NEW YORK CITY – The substantial and ongoing growth in therapeutic options for atopic dermatitis (AD) means that treatments can be personalized across phenotypes, specific symptoms, and patient goals, according to an expert who has published frequently on this inflammatory skin disease.

It is not just more choices but also more mechanisms of action, forms of administration, and combinations that offer an array of strategies to achieve clear or almost clear skin with no or almost no symptoms, according to Mona Shahriari, MD, associate clinical professor of dermatology at Yale University School of Medicine, New Haven, Connecticut, and director of clinical trials at Central Connecticut Dermatology, Avon, Connecticut.

“We are getting to an era in which good control is not enough. We need to get to great control,” Shahriari said.

The premise of individualized therapy is based on the fact that the clinical burden of AD varies by types and severity of symptoms, not all of which share the same drivers of inflammation, which explains why some therapies work better than others in any given patient, according to Shahriari.

AD Pathophysiology Is Heterogeneous

“It is really no surprise that, given how heterogeneous atopic dermatitis is clinically, the pathophysiology of the disease is also heterogeneous,” explained Shahriari, who addressed the “art of choosing AD therapy” at the 28th Annual Mount Sinai Winter Symposium in New York City.

Soon after the first PDE-4 inhibitor — crisaborole — was approved for AD in 2016, the approval of dupilumab for AD in 2017 introduced the era of biologics, which have now been joined by topical and oral JAK inhibitors. These have largely displaced the nonspecific anti-inflammatory drugs, such as steroids or calcineurin inhibitors, in first-line AD therapy, but Shahriari believes that newer therapies should not be considered similar or interchangeable.

Using a series of cases to make her point, Shahriari explained why she would not hesitate to employ dupilumab in a child more than 6 months of age with a substantial burden of symptoms, including impaired sleep. 

“Some might consider this too aggressive, but I would argue no. Skin does not tell us the whole story,” she said. In addition to the adverse impact of inadequate sleep on the child and the caregiver, she pointed out that there are data to link poor sleep in young children with lower height gain, a reduction in bone mineralization, and learning disabilities.

Citing a 2025 study that found greater height gain in children 6 years of age or older on dupilumab compared with those on placebo over 16 weeks of therapy, Shahriari said, “There are a lot of potential complications if we are not treating aggressively.”

She pointed out that this type of evidence can be compelling to parents who are initially reluctant to employ an injectable biologic for AD in a young child.

In a second case, Shahriari explained why she would include a JAK inhibitor as an alternative to dupilumab for specific goals. For example, in a discussion of options for a teenager about to leave for college, she might discuss oral treatment as a substitute for an injectable drug, particularly those with a high itch burden that would potentially be better controlled with a JAK inhibitor. 

Two Conditions Might Be Treated With One Drug

In another scenario involving patients with AD and concomitant atopic diseases, such as asthma or eosinophilic esophagitis, the interleukin (IL)-4 blockade offered by dupilumab might offer relief against multiple conditions. Similarly, she said that IL-13 blockade offered by tralokinumab or lebrikizumab can provide a strong rationale for these biologics in patients with another autoimmune disorder, such as Crohn’s disease.

If patients stop responding to a biologic or plateau in their response after an adequate trial before achieving an acceptable level of disease control, a level that she said might be defined by many as an Eczema Area and Severity Index (EASI) score of 75 or less, Shahriari suggested that the amount of time to wait before a change in strategy should be limited.

In the case of dupilumab, her first step for an inadequate response is more frequent dosing, including weekly dosing, but she recommended moving to a JAK inhibitor when symptoms persist. She cited a 52-week upadacitinib trial extension in which patients randomly assigned to the dupilumab control arm of the prior 24-week double-blind trial were started on upadacitinib. Most of the patients with an inadequate response to dupilumab at 24 weeks improved when switched to upadacitinib.

Of guidelines to determine when to switch therapies, Shahriari pointed to the Aiming High in Eczema/Atopic Dermatitis (AHEAD) recommendations, published in 2024. These emphasize treat-to-target principles in the context of shared decision-making. Although a 6-month trial of treatment, as recommended, might not be long enough for all patients to achieve an optimal response to a given therapy, Shahriari concurred with the goal of aiming for minimal disease activity, not just a “good enough” response, which she said was considered adequate before the introduction of targeted therapies.

A recently introduced screening gene-expression profile for patients with AD might be one tool to facilitate tailored therapy, according to Shahriari. Introduced just weeks before she spoke at the meeting, the 487-gene screening tool, marketed under the name AdvanceAD-Tx (Castle Biosciences) is designed to help clinicians select between biologics and JAK inhibitors as a first-line therapy for AD, based on their gene expression. 

“This will become more widely available next year, but I think this is showing us the progress we are making toward precision medicine in AD,” said Shahriari, who specified that she has no financial relationship with the company introducing this approach.

When contacted about the AHEAD consensus recommendations, the lead author, Jonathan I. Silverberg, MD, PhD, director of clinical research and contact dermatitis at the George Washington University School of Medicine and Health Sciences, Washington, DC, said they are meant to match treatments with patient goals.

“The AHEAD framework is a fusion of treat-to-target with shared decision-making,” he explained. 

Consistent with the concept that AD is heterogeneous and treatment should be tailored to patient goals, “it recognizes that almost no two AD patients are exactly the same, and each has a different symptom complex and consequently different treatment priorities,” Silverberg told Medscape Medical News.

Shahriari reported financial relationships with AbbVie, Bristol Myers Squibb, Cara, Dermavent, Dermira, Eli Lilly, Regeneron, Sanofi, UCB, and Union. Silverberg reported financial relationships with AbbVie, Anacor, AnaptysBio, Arena, Celgene, Dermavent, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Glenmark, Incyte, Kiniksa, LEO Menlo, Novartis, Realm, Regeneron, and Sanofi.