DENVER — Selecting a first-line therapy for moderate-to-severe atopic dermatitis (AD) has been made more complicated by the large number of recent regulatory approvals, but a series of specific questions can provide guidance, according to an expert who has been involved in many of the drug trials.

The questions that clinicians should pose to themselves and to patients include those that elicit a history of infections or autoimmune disease, relative comfort with injections, and the severity of complaints regarding itch relative to rash, according to Matthew J. Zirwas, MD, who is affiliated with Bexley Dermatology in Columbus, Ohio.

In a focus on AD drug selection in adults, Zirwas provided a checklist to help clinicians consider specific characteristics in relationship to the available therapies. 

Questions Are Unique to Adult AD Therapies 

“For the most part, adult-onset AD is acquired, not-flexural, and is associated with no or minimal history of atopic comorbidities, including childhood AD,” said Zirwas. 

He maintained that the options in adults are generally quite different than in children, when he outlined his approach in a presentation at the Society of Dermatology Physician Associates (SDPA) Annual Summer Conference 2026. 

The questions he uses to guide treatment selection is based on more than 25 variables. He did not compare all systemic therapies currently approved for moderate-to-severe AD for each of these variables, but he provided a sample of differences between selected therapies. 

The AD treatments he reviewed were the anti-immunoglobulin E (IgE) monoclonal antibody dupilumab, which blocks interleukin (IL)-4/IL-13 signaling; the anti-IL-31RA monoclonal antibody nemolizumab; the JAK inhibitors abrocitinib and upadacitinib; and the anti-IL-13 monoclonal antibodies tralokinumab and lebrikizumab. He grouped the two JAK inhibitors together because of their similarities, but he discussed relative strengths of the anti-IL-13 monoclonal antibodies separately because of their differences. 

Of the 25 variables Zirwas evaluated, he only cautioned about two absolute contraindications. These involve the use of JAK inhibitors abrocitinib and upadacitinib for patients with a known pregnancy or a solid-organ malignancy. Both contraindications are reflected in their labels.

By some measures, JAK inhibitors are among the most versatile of the therapies used for moderate to severe AD, according to Zirwas. He identified them as attractive for patients with comorbid psoriasis or psoriatic arthritis, and any other comorbid autoimmune disease known to be responsive to JAK inhibitors.

Zirwas also considers JAK inhibitors attractive for treatment of patients with substantial itching looking for fast relief, for patients who have a preference for an oral therapy, and for those who find it difficult to refrigerate their medications, such as those who travel frequently. 

Dupilumab is also versatile and it was the only drug on his list that he thinks should be considered in patients with a known pregnancy. He also considers dupilumab a particularly good choice for those with meaningful atopic comorbidities, comorbid eosinophilic esophagitis, and comorbid chronic obstructive pulmonary disorder. Zirwas credited the anti-IgE mechanism of dupilumab for its efficacy in patients with this profile.

Although tralokinumab, lebrikizumab, and nemolizumab require injections and are not well accepted by those who prefer an oral therapy, Zirwas said that these drugs, along with dupilumab, are well tolerated. Moreover, they are not strongly associated with increased risk for infections, including viral infections, or with increased risk for major adverse cardiovascular events (MACE) or venous thromboembolism (VTE). 

Among the monoclonal antibodies, Zirwas singled out nemolizumab as “probably the fast biologic for relieving itch.” While this makes nemolizumab a good first-line choice hen itch is the chief complaint, Zirwas considers this drug to be slower than other monoclonal antibodies for resolving rash.

With the exception of deucravacitinib, all oral JAK inhibitors carry a boxed warning in their labelling that refers to the increased risk for MACE, VTE, and serious infections. However, Zirwas is not convinced that the risk for MACE and VTE, which gained that boxed warning based on a 2022 study in patients with rheumatoid arthritis already at risk for MACE, is relevant to their use in AD. 

Based on his review of the evidence, including real world data, he said that no study has convincingly demonstrated an increased risk for MACE or VTE in patients with AD taking a JAK inhibitor.

Zirwas noted that his opinions about current AD therapies are his own and not based on guidelines, but his presentation provided an opportunity to emphasize the importance of individualizing therapy based on drug and patient characteristics.

The potential for confusion among clinicians faced with numerous approved systemic therapies for AD has been addressed by others. Angela J. Lamb, MD, director of the Westside Mount Sinai Dermatology Faculty Practice, which is affiliated with the Icahn School of Medicine at Mount Sinai in New York, was senior author of a clinical review of systemic AD therapies published in March of this year.

“There are no guidelines yet to direct choices according to phenotype,” said Lamb, but she agrees with the principle that the systemic therapies are not interchangeable. In her paper, she and her colleagues argued that “the expanding treatment landscape necessitates individualized therapy selection.” 

For people who treat AD regularly, the key variables to consider are quickly memorized and incorporated into patient care, Lamb told Medscape Medical News. Yet, a review of these variables, like the one included in her paper, can quickly remind clinicians what “should be kept top of mind.”

“Generally, these considerations will help you narrow down the choice very rapidly so that you are selecting between one or two therapies instead of 10,” she said. 

“We are likely to have a more sophisticated method of choosing one drug over another as we have more data or if comparative trials are conducted,” Lamb predicted. Her paper, for example, was not based on a meta-analysis or another form of objective analysis but was an effort to synthesize available data with clinical expertise. 

“I think our paper provides a grounding in the types of differences between drugs and why you might select one over another,” she said.

Zirwas reported financial relationships with AbbVie, Acrotech, Advanced Derm Solutions, Aldeyra, Henkel, Amgen, Anaptys Bio, Apogee, Arcutis, Beiersdorf, Biocon, Boehringer Ingelheim, Bristol-Myers Squibb, Cara, Celldex, Evelo, Evommune, Galderma, Incyte, and Janssen. Lamb reported no potential conflicts of interest.