Personalizing Atopic Dermatitis Care with JAK Inhibitors: Clinical Pearls for Real-World Practice

In this episode of Topical Conversations, Graham Litchman, DO, MS, and Naiem Issa, MD, discuss the role of Janus kinase (JAK) inhibitors in atopic dermatitis (AD). These agents are increasingly valued for their efficacy and safety in clinical practice. A key advantage is the ability to individualize therapy through dose escalation, allowing JAK inhibitors to support a more personalized approach to managing this heterogeneous condition.

Safety considerations

Dr Litchman and Dr Issa review the safety profile of JAK inhibitors, noting that these medications are widely used and generally well tolerated. Large-scale studies of abrocitinib and upadacitinib, encompassing thousands of patients across multiple countries, support their safety and efficacy.

Dr Issa emphasizes the importance of proactively addressing the boxed warning during patient discussions. Many patients will review the package insert and raise concerns, so he begins the conversation by explaining the history and context behind the warning. The boxed warning stems from the ORAL Surveillance study of tofacitinib vs TNF inhibitors in patients with rheumatoid arthritis aged 50 and older with cardiovascular comorbidities; many of these patients were on concomitant methotrexate and often corticosteroids. This population differs significantly from typical patients with AD.

The “big 5” risks listed in the boxed warning (infection, major adverse cardiovascular events, thrombosis, sudden death, and malignancy) are framed as “reports” associated with JAK inhibitors, not as placebo-controlled findings. Dr Issa notes that clarifying this nuance helps patients understand the data in context and alleviates concerns. Dr Litchman adds that while these conversations can be complex, the majority of AD patients are not the same as the population studied in ORAL Surveillance, and most tolerate JAK inhibitors well in practice.

Personalized treatment and dosing strategies

Both experts highlight the role of JAK inhibitors in moving toward personalized medicine for AD, a heterogeneous and fluctuating disease. Treatment plans can be tailored based on individual patient needs, with the ability to adjust dosing when necessary.

Data from studies such as the JADE and LEVEL UP trials support flexible dosing. For example, abrocitinib can be initiated at 100 mg daily, with evidence supporting escalation to 200 mg if additional efficacy is needed. Upadacitinib has a similar dose-response profile, with starting doses of 15 mg and higher efficacy seen with 30 mg. Importantly, long-term safety data have not shown an increased risk of adverse events of special interest when escalating to higher doses.

In practice, Dr Issa often re-evaluates patients within 2 weeks, especially those with itch-dominant disease, and escalates dosing earlier if needed, supported by lab monitoring.  

Biological and mechanistic insights

Beyond clinical outcomes, Dr Litchman highlights emerging data on gene expression changes with JAK inhibitors. Studies suggest that these therapies, like biologics, may help normalize core gene sets associated with AD, particularly those related to itch pathways and skin barrier function. Observing both clinical improvements in itch and skin clearance, alongside genomic changes, reinforces confidence in the biological rationale for JAK inhibitor therapy.

Key takeaways

• Safety in context: Boxed warnings stem from rheumatoid arthritis data; most patients with AD tolerate JAK inhibitors well
• Flexible dosing: Clinical trials support dose escalation (eg, increasing abrocitinib dosage from 100 mg to 200 mg or upadacitinib from 15 mg to 30 mg) without added long-term safety signals
• Biologic rationale: Emerging gene expression data support the mechanistic role of JAK inhibitors in normalizing AD pathways

For a closer look at how dose escalation can influence outcomes in practice, explore a case report authored by Graham Litchman, DO, MS. It details a 25-year-old patient with longstanding, refractory atopic dermatitis who achieved complete clearance on abrocitinib following dose adjustment, with before-and-after photos documenting the clinical response.