Charting a Path to Higher Treatment Targets With JAK Inhibition in Atopic Dermatitis

During the Fall Clinical 2025 session, “Charting the Course to Higher Targets with JAK Inhibition in Atopic Dermatitis,” Linda F. Stein Gold, MD; Christopher G. Bunick, MD, PhD; and David Cotter, MD, PhD, addressed the evolving role of Janus kinase (JAK) inhibitors in the management of moderate-to-severe atopic dermatitis (AD). The session focused on elevating therapeutic expectations in AD care, analyzing data on existing JAK inhibitors, and encouraging dermatologists to challenge treatment inertia.

Dr Bunick opened with a discussion on the AHEAD (Aiming High in Eczema and Atopic Dermatitis) initiative, a global task force of 87 experts that established consensus recommendations for achieving optimal treatment outcomes in AD.

AHEAD proposes that optimal outcomes—both clinical and patient-reported—should be achieved within 3 to 6 months of initiating therapy. These targets include:

• Eczema Area and Severity Index 90 or Investigator’s Global Assessment 0/1 for skin clearance
• Itch Numerical Rating Scale 0/1 for pruritus resolution

“The goal is not just skin clearance but symptom control,” said Dr Bunick. “Itch resolution is the single most important patient-reported outcome that impacts quality of life for our AD patients.”

He emphasized that itch control, even more than skin clearance alone, correlates with better quality of life across multiple patient-reported domains, including sleep, function, and emotional well-being.

The data presented reinforced the value of composite endpoints. Patients achieving both skin clearance and itch resolution had the highest odds of achieving low Dermatology Life Quality Index scores and improvements in pain and sleep. “Achieving both simultaneously—not just one—is what really makes a difference,” Dr Bunick noted.

However, data from the TARGET-DERM registry showed a stark contrast between these ideals and real-world outcomes. Among patients treated primarily with dupilumab:

• Only ~20% achieved optimal skin targets over 12 months
• Less than 20% met optimal itch control thresholds

“These are patients we’re keeping on therapy, often for long periods, without hitting targets,” said Dr Bunick. “This reflects a pattern of treatment inertia. We need to recognize when therapy isn't working and be prepared to switch.”

Dr Stein Gold emphasized the clinical tendency to maintain patients on suboptimal regimens, particularly in biologic therapy. “We don’t always push for higher endpoints,” she noted. “But we have the tools to do so now.”

Dr Cotter agreed, underscoring the need to challenge ingrained prescribing habits, particularly the persistent reliance on systemic corticosteroids.

Dr Cotter reviewed the 2025 American Academy of Dermatology treatment guidelines, which rank currently approved systemic therapies by strength of recommendation. The top tier includes:

• Biologics (dupilumab, tralokinumab, lebrikizumab)
• JAK inhibitors (abrocitinib, upadacitinib)

Significantly, these options were recommended above phototherapy and traditional immunosuppressants (methotrexate, cyclosporine, azathioprine), which carry higher toxicity risks and are not US Food and Drug Administration approved for AD.

Corticosteroids were strongly discouraged. “Systemic steroids get a bright red ‘no,’” said Dr Cotter. “They may have been acceptable 60 years ago, but not now.”

The updated consensus calls for eliminating routine systemic steroid use. “If you’re reaching for oral steroids, you should be reaching for a JAK inhibitor instead,” he said.

Despite mounting evidence and clear guidelines, Cotter cited data showing that:

• 1 in 5 patients with AD still receives systemic steroids
• 1 in 4 patients is on steroids for 3 months or longer

“These numbers are unacceptable,” he said. “The risks far outweigh any short-term benefit.”

He referenced an expert consensus statement recommending that any systemic steroid exposure, regardless of dose or duration, qualifies as a systemic therapy trial, thereby making the patient eligible for advanced nonsteroidal treatments.

“Even a single injection or 5-day taper should be considered a trial. That’s enough to warrant escalation,” said Dr Cotter.

The panelists encouraged dermatologists to adopt a new mindset: Treat early, treat aggressively, and aim for complete disease control. The availability of safe, effective JAK inhibitors supports this evolution.

“When you have therapies with high efficacy, fast onset, and oral administration like JAK inhibitors you can truly tailor treatment,” said Dr Stein Gold.

Dr Cotter added, “We have the data and the tools. The challenge now is in the habits. It’s time to move beyond what we used to do.”

The speakers urged dermatologists to reflect on whether their patients are truly thriving and if not, to be proactive in pursuing newer, better options.

“Don’t just aim for good enough,” said Dr Bunick. “We can and should aim for clear.”

Reference
Bunick C, Cotter D, Stein Gold L. Charting the course to higher targets with JAK inhibition in atopic dermatitis. Presented at: 2025 Fall Clinical Dermatology Conference. October 23–26, 2025; Virtual.