JAKs, STATs, and New Targets in Inflammatory Skin Disease

At the 2025 Inflammatory Skin Disease Symposium (ISDS) in New York, New York, Massimo Gadina, PhD, editor in chief of the journal Inflammation and adjunct professor at Georgetown University, shared key perspectives on the evolving therapeutic landscape for inflammatory and immune-mediated dermatologic conditions. Although not a dermatologist by training, Gadina emphasized the value of interdisciplinary dialogue, noting that the meeting is “a place where I always learned a lot... about pathology, of different dermatological diseases.”

A central theme of his presentation was the continued relevance and expansion of Janus kinase (JAK) inhibitors for both rheumatologic and dermatologic indications. According to Gadina, “JAK inhibitors are still a class of drugs that are very, very useful to treat not only rheumatologic diseases but also skin diseases.” Originally developed for systemic autoimmune conditions, these agents have progressively entered dermatology, supported by growing clinical data and multiple regulatory approvals across inflammatory skin disorders.

While acknowledging ongoing questions regarding long-term safety, Gadina emphasized that “overall, I think they're still a good, very safe drug compared to others used to treat various patients.” As of his discussion, 14 JAK inhibitors have been approved globally for a range of diseases, with many more in development—an indicator that the field remains highly active and competitive. He added that “many more drugs are coming to the market,” suggesting that JAK inhibition will continue to expand as mechanistic understanding deepens.

Beyond JAK inhibition, Gadina highlighted emerging molecular strategies that may reshape future therapeutic design. These include siRNA-based approaches and targeted protein degradation technologies such as PROTACs. These modalities offer the possibility of degrading specific intracellular proteins rather than merely inhibiting their enzymatic activity. Gadina noted their potential relevance not only for JAK proteins but also for STAT transcription factors, which are traditionally more challenging to target.

He further underscored the increasing importance of integrating clinical medicine, genetics, and drug development. The growing ability to identify polymorphisms associated with autoimmune and inflammatory skin diseases may enable more precise targeting of therapies. As he explained, the goal is to treat “specific population[s] with drugs rather than giving it to everybody,” thereby improving efficacy and reducing unnecessary exposure.

Gadina concluded by emphasizing that the future lies in robust interdisciplinary collaboration, stating that the partnership between “geneticists, clinician and drug developer…is something to look forward to.” As dermatology continues to intersect with molecular immunology, these integrated approaches may help define the next generation of personalized therapies for inflammatory skin disease.