The Future of Dermatology: Precision, Pathways and Raising the Bar
The landscape of dermatological treatment is undergoing a significant shift, moving beyond broad-spectrum approaches toward therapies that target specific biological pathways. This evolution, highlighted by Dr. Christopher Bunick, MD, PhD, at the South Beach Symposium 2026, promises more effective and safer treatments for chronic inflammatory skin diseases like atopic dermatitis (AD), psoriasis, and hidradenitis suppurativa (HS).
Beyond TH2: The Complexity of Atopic Dermatitis
Atopic dermatitis, long understood to be driven by TH2 cytokines, is now recognized as a far more complex condition. “In AD, we know that the underlying pathophysiology, it’s very heterogeneous, meaning there’s multiple cytokines that drive atopic dermatitis,” explains Dr. Bunick. Whereas existing biologics targeting TH2 have been transformative, they don’t address the full spectrum of the disease. The next generation of therapies focuses on bispecific and trispecific biologics, designed to simultaneously target multiple inflammatory pathways for deeper skin clearance, itch and pain control, and improved quality of life.
TYK2 Inhibition: A New Era of Selectivity
Selective intracellular signaling inhibitors, particularly those targeting tyrosine kinase 2 (TYK2), are gaining prominence. Unlike traditional JAK inhibitors that broadly impact the JAK family, TYK2 inhibitors offer a more targeted approach. Dr. Bunick clarifies, “What really differentiates TYK2 inhibitors from JAK inhibitors is exactly what they are targeting in this family of JAK enzymes.” These inhibitors act on the regulatory domain of TYK2, maximizing selectivity and minimizing off-target effects.
Deucravacitinib, the first-generation TYK2 inhibitor, has demonstrated sustained efficacy in psoriasis with a reassuring safety profile over four years, showing no increased risk of malignancy, cardiovascular events, or blood clots compared to baseline rates. Next-generation TYK2 inhibitors, zasocitinib and envudeucitinib, are being developed for even greater selectivity, with phase 3 data for zasocitinib anticipated soon. While acneiform eruptions and folliculitis have been observed, they are generally manageable.
The safety of targeting TYK2 is further supported by genetic evidence – naturally occurring human variants with reduced TYK2 function are associated with lower rates of immune-mediated diseases.
Expanding Horizons: TYK2 and JAK Inhibitors Beyond Psoriasis
The potential of JAK and TYK2 inhibitors extends beyond psoriasis. Researchers are exploring their use in vitiligo, alopecia areata, dermatomyositis, and hidradenitis suppurativa. However, Dr. Bunick emphasizes the need for more ambitious clinical trial endpoints, particularly in HS. “I really wanna see the endpoint bar being raised,” he states, advocating for therapies that move beyond modest response rates toward truly transformative outcomes.
Did you know? Naturally occurring genetic variations that reduce TYK2 function are linked to a lower risk of autoimmune diseases, suggesting a strong biological rationale for TYK2 inhibition.
The Rise of Pathway Specificity and Durable Control
These advancements collectively represent a fundamental shift in dermatology. The future is defined by pathway specificity, improved safety profiles, and a growing expectation for durable disease control. This precision-focused approach promises to deliver more effective and personalized treatments for patients suffering from chronic inflammatory skin conditions.
Frequently Asked Questions
Q: What are bispecific and trispecific biologics?
A: These are advanced biologics designed to target multiple inflammatory pathways simultaneously, offering a more comprehensive approach to disease control.
Q: What is TYK2 and why is it a promising therapeutic target?
A: TYK2 is a tyrosine kinase involved in immune signaling. Inhibiting it offers a selective way to modulate the immune response with a potentially improved safety profile.
Q: What are the potential side effects of TYK2 inhibitors?
A: Acneiform eruptions and folliculitis have been observed, but are generally manageable.
Q: What is the future outlook for HS treatment?
A: There is a need for clinical trials with more ambitious endpoints to demonstrate truly transformative outcomes.
Pro Tip: Staying informed about the latest research in dermatology is crucial for both patients and healthcare professionals. Resources like the South Beach Symposium offer valuable insights into emerging therapeutic strategies.
What are your thoughts on the future of dermatology? Share your comments below!
