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Targeting the JAK-STAT Pathway in AD

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.

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.

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

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