TYK2 Inhibition in Psoriasis: New Pathways, New Possibilities
At Dermatology Week 2025, Dr Jeffrey Cohen and Dr Alice Gottlieb brought attendees inside the data, mechanisms, and evolving landscape of TYK2 inhibition in their session, “Targeting TYK2: Innovative Strategies to Advance Psoriasis Care and Outcomes.”
“Psoriasis is an inflammatory skin and systemic disease impacting about 125 million individuals globally,” Dr Cohen said, opening the session. He walked attendees through the immune activation cascade, starting with environmental triggers that lead to dendritic cell activation, T-cell differentiation, and the inflammatory IL-23/IL-17 axis. “TYK2 inhibitors prevent downstream signaling from the IL-23 inflammatory pathway, which we know is quite central to psoriasis,” he explained.
Dr Cohen offered a helpful patient analogy: “I think of the cytokine as a piece of mail. The receptor is the mailbox. TYK2 is what opens the letter and gets the signal going. Inhibiting it stops the message from being read.”
Importantly, TYK2 inhibitors act through allosteric inhibition, not by directly blocking the active site. “They have very little impact on JAK1, 2, or 3, which allows for a very favorable safety profile,” Dr Cohen noted. Unlike traditional Janus kinase inhibitors, TYK2 agents do not have the same black box warnings or rates of serious infections.
He highlighted 3 oral TYK2 inhibitors: deucravacitinib, zasocitinib, and ESK-001. Deucravacitinib has been US Food and Drug Administration approved since 2022, demonstrating sustained efficacy out to 4 years in the POETYK PSO-1 and PSO-2 trials. In both studies, more than half of patients achieved Psoriasis Area and Severity Index (PASI) 75 by week 16.
Zasocitinib may offer higher potency, although it is still investigational. “The higher dose ranges—15 and 30 mg per day—tended to perform the best,” said Dr Cohen. ESK-001 also showed promising PASI 75 responses with strong 52-week durability.
Dr Alice Gottlieb followed with a broad overview of real-world psoriasis care, from updated guidelines to combination strategies and special populations. She emphasized psoriatic arthritis (PsA) screening: “PsA is the most common comorbidity of psoriasis, and it goes undiagnosed in 40% of cases by dermatologists.” She urged attendees to use tools like the Psoriasis Epidemiology Screening Tool and the Psoriatic Arthritis Impact of Disease-12 questionnaire, which have helped her team flag patients early.
Gottlieb closed with a call to action: “We have highly effective and safe treatments. The challenge is access and making sure patients get the right treatment based on all aspects of their disease.”
For more meeting coverage, visit the Dermatology Week newsroom.
Maximize your experience by adding up to 90 days of on-demand access. Find the package that works for you. Upgrade here.
Reference
Cohen J, Gottlieb A. Targeting TYK2: innovative strategies to advance psoriasis care and outcomes. Presented at: Dermatology Week; October 22–25, 2025; Virtual.
