Christopher G. Bunick, MD, PhD

Indications and Efficacy of JAK Inhibitors for AD

This is a video synopsis/summary of a panel discussion involving Christopher Bunick, MD, PhD; Peter Lio, MD; Lisa Swanson, MD, PhD; and Alexandra Golant, MD.

Lisa Swanson, MD, PhD, discusses FDA-approved topical and systemic Janus kinase (JAK) inhibitors for atopic dermatitis, addressing their indications and clinical trial data. Topically, ruxolitinib is approved for patients aged 12 and older with nonsegmental vitiligo or mild to moderate atopic dermatitis, demonstrating significant efficacy at 8 weeks. Orally, abrocitinib and upadacitinib are daily pills for patients aged 12 and older, with flexible dosing based on response.

Clinical trial data, including the TRuE-AD1 and TRuE-AD2 trials for ruxolitinib and studies comparing upadacitinib and abrocitinib to dupilumab, is reviewed. Ruxolitinib shows rapid efficacy, with about half of the patients achieving IGA (investigator lobal assessment scale) clear or almost clear at 8 weeks. Comparisons with dupilumab reveal that upadacitinib at 100mg is as effective, while the 200mg dose appears slightly more effective. In head-to-head studies, upadacitinib at 30mg outperforms dupilumab.

Dr Swanson also mentions the ongoing Level Up study comparing upadacitinib 15mg to dupilumab and discusses network meta-analyses evaluating advanced therapies. Despite challenges in indirect comparisons, these analyses suggest that upadacitinib at 30mg is superior to upadacitinib at 15mg, which is superior to abrocitinib at 200mg, and abrocitinib at 200mg is superior to dupilumab at 300mg every two weeks.

The discussion concludes with the analogy of treating atopic dermatitis as the Olympics, where JAK inhibitors, specifically abrocitinib and upadacitinib at certain doses, take gold, silver, and bronze, reflecting the revolutionary efficacy and impact on itch in the field.

Video synopsis is AI-generated and reviewed by HCPLive editorial staff.

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Lisa Swanson, MD, PhD, reviews the indications for ruxolitinib, abrocitinib, and upadacitinib, as well as the clinical trial data on efficacy of these JAK inhibitors when treating AD.

Differentiating JAK Inhibitors From Other Therapies in AD

Dr Peter Lio, MD, discusses the distinguishing features of JAK (Janus kinase) inhibitors in the context of treating atopic dermatitis. He emphasizes 2 significant aspects that set JAK inhibitors apart from other therapies. Firstly, in the realm of systemic treatments, where there were limited approved options until recently, biologic agents targeting specific cytokines required subcutaneous injections and had a slower onset. In contrast, JAK inhibitors, administered orally, exhibit a remarkably rapid response within hours to days, offering a level of disease control that surpasses previous treatments.

The focus on itch as a crucial aspect of atopic dermatitis treatment is highlighted. Dr Lio refers to a study published in the British Journal of Dermatology, revealing the substantial improvement in quality of life for patients achieving an itch level of zero or 1. The conversation emphasizes the need to address itch comprehensively, not just focusing on skin signs. Achieving itch scores of zero or 1 is identified as a crucial goal for optimal patient outcomes.

The discussion underscores the transformative impact of JAK inhibitors in the field, offering a new tool that informs a "treat to target" approach. The ability to aim for zero itch, coupled with the rapid efficacy of JAK inhibitors, has raised the standards for treating atopic dermatitis. The conversation among the experts reflects a consensus that JAK inhibitors have elevated the efficacy bar, not only in terms of skin clearance but also in addressing itch and improving overall quality of life for patients. The introduction of these inhibitors has empowered clinicians to ask different questions and strive for a higher standard of care, ultimately benefiting patients with atopic dermatitis.

Expert dermatologists discuss the factors that differentiate JAK inhibitors from other AD therapies, highlighting itch scores as they relate to quality of life.

targeting the JAK-STAT (signal transducer and activator of transcription) pathway with JAK inhibitors plays a role in managing AD.

Targeting the JAK-STAT Pathway in AD

This is a video synopsis/ summary of a panel discussion involving Christopher Bunick, MD, PhD; Peter Lio, MD; Lisa Swanson, MD, PhD; and Alexandra Golant, MD.

In this discussion, Dr Alexandra Golant, MD, explores the role of targeting the JAK-STAT pathway in managing atopic dermatitis symptoms, including itch and inflammation. The conversation begins with the acknowledgment of atopic dermatitis's clinical heterogeneity and the evolving understanding of systemic inflammation beyond the traditional TH2-dominant perspective. Dr Golant highlights the complexity of cytokine involvement in atopic dermatitis, suggesting that each patient may have a unique cytokine offering, contributing to the varied presentation of the disease.

The effectiveness of medications targeting the JAK-STAT pathway is emphasized, particularly in comparison to drugs that focus on the signaling of individual cytokines. By targeting a messenger responsible for mediating signaling for a group of cytokines, these medications offer a broader inhibition of inflammation. The JAK-STAT pathway is identified as a key mediator for various cytokines.

The conversation delves into the shift from viewing atopic dermatitis solely as a TH2-driven disease to recognizing the involvement of TH-17 and TH-1 cytokines in some patients. Dr Golant discusses the importance of tailoring therapies to specific cytokine signatures, highlighting the complexity of cytokine interactions in the disease. The concept of a molecular endotype is introduced as a buzz term, emphasizing the need for a deeper understanding of the molecular signatures of atopic dermatitis patients and the role of cytokines in disease progression. The JAK inhibitors are portrayed as a “Goldilocks” solution—broader than targeting 1 or 2 cytokines but not excessively broad in immunosuppression. The term "molecular endotype" is identified as crucial for dermatologists to comprehend the evolving landscape of atopic dermatitis treatment.

Alexandra Golant, MD; Christopher Bunick, MD, PhD; and Peter Lio, MD, comment on how targeting the JAK-STAT (signal transducer and activator of transcription) pathway with JAK inhibitors plays a role in managing AD.

 provide an overview of Janus Kinase (JAK) inhibitors, their pathophysiology, and their mechanism of action in the treatment of atopic dermatitis (AD).

Intro to Janus Kinase (JAK) Inhibitors for Treatment of Atopic Dermatitis (AD)

In this segment, Peter Lio, MD, introduces Janus kinase (JAK) inhibitors and their significance in molecular signaling pathways, particularly in diseases like atopic dermatitis. Originally named "just another kinase," JAKs play a crucial role in cellular signaling, with subtypes such as JAK1, JAK2, JAK3, and TKY2 (tyrosine kinase 2) associated with various diseases. Dr Lio explains that when inflammatory cytokine messages are transmitted between cells, they activate JAKs through conformational changes in receptor proteins. This, in turn, activates statin, influencing gene transcription in the nucleus.

Reflecting on the past, the discussion shifts to the initial belief that the JAK-STAT pathway was not druggable. Lisa Swanson, MD, PhD, highlights the progress, especially in the treatment of atopic dermatitis. The mechanism of JAK inhibitors is explored, focusing on their ability to interrupt the inflammatory process driven by cytokines binding to cell receptors. By inhibiting JAKs, the cascade of inflammatory processes is disrupted, impacting various cytokines and their role in gene transcription.

The conversation emphasizes the evolving understanding of atopic dermatitis as a multi-cytokine disease, with JAK inhibitors providing insights into the heterogeneity of the condition. The inhibitors not only address inflammation but also contribute to a deeper comprehension of the role of different cytokines in both skin inflammation and itch. Overall, the discussion underscores the transformative impact of JAK inhibitors in the field of dermatologic treatment and research.

Peter Lio, MD, and Lisa Swanson, MD, PhD, provide an overview of Janus Kinase (JAK) inhibitors, their pathophysiology, and their mechanism of action in the treatment of atopic dermatitis (AD).

Christopher G. Bunick, MD, PhD

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