<p>TYK2 inhibition is a promising pathway for the treatment of plaque psoriasis, especially with the option of using an oral agent. At the <strong>2025 Fall Clinical Dermatology Conference</strong>, the current landscape of oral therapy for plaque psoriasis was discussed, with a focus on emerging treatment options in TYK2 inhibition.</p> <p><br></p> <p><em>Following these presentations, featured expert Raj Chovatiya, MD, PhD, MSCI, was interviewed by </em>Conference Reporter<em> Associate Editor-in-Chief Christopher Ontiveros, PhD. Clinical perspectives from Dr Chovatiya on these findings are presented here.</em></p>

TYK2 is 1 of 4 proteins in the JAK family. This family is important for signal transduction, with effects on transcription, translation, and the production of a variety of downstream gene products. The JAK proteins are important components of the immune system for many soluble cytokine signaling functions. These cytokines have broad roles in immune function, metabolism, hematopoiesis, and other core biologic functions. TYK2 is more specific than JAK1, JAK2, and JAK3 in its role related to immune system activation and inflammation. TYK2 mediates signaling by IL-12, IL-23, and type I interferons, which are important to the pathogenesis of plaque psoriasis. This is why TYK2 inhibition has been an attractive candidate for treatment.

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The first medication to be developed and launched in this category for plaque psoriasis was deucravacitinib. The concept of an oral medication that is highly selective and specific for a core pathway involved in plaque psoriasis was welcome, considering that most of our effective treatments have been biologics, and previous oral therapies had far lower efficacy than injectables. While most oral JAK inhibitors are broadly acting active site inhibitors of the JAK proteins, meaning that they can be highly selective but not entirely specific, deucravacitinib has a unique mechanism of action. It was the first agent to uniquely bind to the regulatory domain of TYK2, an allosteric site that controls enzyme activity. Thus, it is able to effectively block TYK2 activation and leave JAK1, JAK2, and JAK3 relatively untouched. This is a likely reason why a high degree of efficacy has been observed in clinical trials without some of the safety concerns and potential severe warnings that are often associated with the JAK inhibitor class.

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Deucravacitinib has shown promising short- and long-term efficacy and safety in multiple clinical trials. In general, patients had durable responses over time, and the safety issues that we tend to associate with traditional, more nonspecific oral JAK inhibitors, including major adverse cardiovascular events, malignancies, thrombosis, and serious infections, were not prominently observed. Deucravacitinib was discussed at the 2025 Fall Clinical Dermatology Conference in a presentation by James Q. Del Rosso, DO, and Benjamin Lockshin, MD, with a focus on progressive updates, including 5-year data that show consistent safety and durable response rates.

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Beyond deucravacitinib, additional clinical development is ongoing in the TYK2 inhibitor class. This was a major topic of discussion at this year’s meeting in multiple presentations. Recent phase 2 study data have shown promising results for 2 new TYK2 inhibitors: zasocitinib and envudeucitinib. Both of these TYK2 inhibitors have a similar mechanism of action to deucravacitinib. Although we are awaiting phase 3 data readouts, it is exciting to know that we may soon have even more oral treatment options for patients.

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We have seen major therapeutic advancements in the injectable space for plaque psoriasis, but innovations in oral therapies have not kept the same pace. The fact that we now have a medication like deucravacitinib—and potentially 2 more in the TYK2 inhibitor class knocking at the door, with zasocitinib and envudeucitinib—means that we will have the ability to have a substantial conversation about oral treatment options with our patients. This is a big deal in dermatology, as we often assume that we know what our patients want in terms of therapeutic choice. With more treatment options that offer high levels of efficacy with strong safety profiles, we can more practically ask our patients about their preferences in route of administration without any substantial trade-offs.

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Therapeutic innovation in plaque psoriasis is not stopping. There is continued interest in oral therapies, with TYK2-related agents and beyond. Over the coming years, I hope that even more innovative oral options will allow patients to experience biologic levels of both efficacy and safety.