Overcoming Treatment Inertia to Improve Outcomes in Atopic Dermatitis

In the era of targeted therapies, practitioners have a myriad of new tools at their disposal, which enable them to raise the standards of care for patients with atopic dermatitis (AD). The modern management of AD involves navigating this complex therapeutic landscape and identifying the treatments that can deliver the goals that are most relevant to individual patients. During this year’s Fall Clinical Dermatology Conference, in Las Vegas, Nevada, a panel of experts reviewed recommendations and outlined strategies for counseling patients with moderate-to-severe AD about treatment options that can improve treatment response and outcomes in this population. 

“We have a lot of treatment inertia and we don’t always go for these higher [treatment] targets,” said Linda Stein Gold, MD, director of dermatology clinical research at Henry Ford Health System in Detroit, Michigan. “We now have some tools that are actually going to help us get there.” 

The consensus-based Aiming High in Eczema/Atopic Dermatitis (AHEAD) recommendations were designed to guide clinicians toward treatments that can achieve results early, within 3 to 6 months. While older treatment targets for AD were more modest, the AHEAD task force established a composite of outcomes including clear skin, defined as Eczema Area and Severity Index (EASI)-90 or Investigator's Global Assessment (IGA) scores of 0 to 1, and low itch scores (Worst Pruritus Numerical Rating Scale [WP-NRS] 0 or 1) as the standard for minimal disease activity. “Itch resolution is the single most important patient-reported outcome that impacts quality of life for AD patients,” said Christopher Bunick, MD, PhD, an associate professor of dermatology at the Yale School of Medicine in New Haven, Connecticut. “If you achieve high itch response, meaning itch scores of 0 or 1, regardless of whether you are above EASI-90 or slightly below EASI-90, these patients have very high quality of life.” 

While achieving both near-complete itch relief and clear or almost clear skin leads to dramatic improvements in quality of life, sleep, and symptoms, real-world data revealed that the percentages of patients who meet the optimal treatment targets recommended by AHEAD remain low, even among those on long-term systemic therapy. “We have gotten into a habit of keeping patients long-term on a treatment, maybe dupilumab, maybe something else, even when they are not hitting an optimal treatment target, Bunick noted. “The AHEAD recommendations want us to move past that, to be comfortable saying that we are not hitting that target, [that] it is time to move to a new therapy. We want to break the cycle of treatment inertia.”     

The latest recommendations issued by the American Academy of Dermatology are moving the needle in the direction of targeted therapies and away from traditional treatment with systemic corticosteroids. Nevertheless, treatment targets and strategies should be tailored to the needs and preferences of individual patients. “We are always striving for the best treatment,” said David Cotter, MD, PhD, a dermatologist based in Las Vegas. “But the best treatment is the best [option] for that patient sitting across from you in the exam room, and that might be a biologic, it might be a Janus kinase (JAK) inhibitor. So, we dig down into what the patients’ goals of treatment are and what their risk threshold is.” Presenting different options and discussing the risk-benefit profiles of different medications enables patients to make informed decisions and places them at the center of the treatment plan. 

Bunick reviewed data from head-to-head clinical trials comparing the efficacy of two systemic JAK inhibitors, upadacitinib and abrocitinib, against the results achieved with dupilumab. The studies showed that, overall, treatment with JAK inhibitors led to higher rates of skin clearance and stringent itch relief, and achieved symptom relief earlier than dupilumab. Long-term data from the Measure Up 1 and Measure Up 2 randomized phase 3 trials showed that adolescents and adults with AD treated with upadacitinib achieved a sustained response of both EASI-90 and WP-NRS of 0 or 1 over 140 weeks. 

Safety studies for upadacitinib previously showed that the incidence rates of malignancy, major adverse cardiovascular events (MACE), and venous thromboembolism (VTE) reflected the background rates seen in the population living with AD. New data presented at the Fall Clinical conference reinforced those findings, showing that upadacitinib had similar rates of cardiovascular events and malignancy as tralokinumab, a biologic therapy that targets interleukin-13. 

While biologic therapies have earned their place in the armamentarium for the treatment of AD, JAK inhibitors provide additional options for tailoring AD management. “One thing that is wonderful is that we don’t have to just play the odds or guess what the best drug for any individual patient will be, because on the horizon is a new gene expression profiling test that can be utilized when treating atopic dermatitis,” Cotter added. A sample collected by superficial skin scraping will provide valuable information about individual patients’ projected response to different therapies, including biologic therapies and JAK inhibitors.