Oral therapies remain an important treatment option for patients with moderate to severe plaque psoriasis. At the recent 2026 Fall Clinical Dermatology Conference, experts reviewed advances in TYK2 inhibitors for the disease, highlighting clinical trial data for available and pipeline agents.

Following this presentation, featured expert Diego Ruiz Dasilva, MD, FAAD, was interviewed by Conference Reporter Associate Editor-in-Chief Rick Davis, MS, RPh. Clinical perspectives from Dr Ruiz Dasilva on these findings are presented here.

There are many excellent injectable treatment options for moderate to severe plaque psoriasis, but it is interesting how things have evolved over time. Early on, there was a preference for oral therapies. Even when injectable therapies became popular, it was largely because the oral therapies that were available at the time were less effective or had higher toxicity rates, not because patients were looking for injectable therapies from the get-go. Now, we are circling back to highly effective oral therapies, including PDE4 inhibitors, TYK2 inhibitors, and IL-23R antagonists. Depending on the region, demographic surveys still indicate a big preference for oral treatment options among patients.

Often, patients find oral agents to be easier to take. They do not have to refrigerate the drug, worry about when shipments will arrive, or worry about whether the drug will stay cold, particularly when they are traveling or on vacation. There is also some anxiety among patients associated with having to inject themselves or ask a family member or friend to administer the injection for them. This is why oral therapies are here to stay, even if they never become as good as or better than injectable therapies.

We work with patients and discuss the benefits and risks of both treatment options. Some patients prefer not to have to take yet another oral therapy, while others prefer injectable therapies so that they do not have to remember to take their medication daily. Having oral options available is also a very natural transition for a patient with moderate to severe plaque psoriasis who has been on topical therapies all along and does not feel quite ready to move on to an injectable therapy.

The presentation at the 2026 Fall Clinical Dermatology Conference titled “The Next Chapter in Psoriasis Therapy: The Role of New and Emerging TYK2 Inhibitors,” which was presented by Edward Lain, MD, MBA, Linda F. Stein Gold, MD, and Ronald Vender, MD, focused on the TYK2 signaling pathway. The primary concept is that TYK2 is part of the JAK/STAT family, which includes JAK1, JAK2, JAK3, and TYK2. TYK2 is more involved in signaling through the IL-23, IL-12, and type I interferon pathways, which are well established in plaque psoriasis, rather than other cytokine pathways that are involved in atopic dermatitis and other immune-mediated diseases. The goal is also to avoid affecting the JAK2, JAK3, or even JAK1 pathways that are involved in hematopoiesis, thrombopoiesis, and lymphocyte activation, hopefully resulting in fewer off-target effects.

In the same presentation at the conference, clinical data for deucravacitinib and the pipeline TYK2 inhibitor zasocitinib were also reviewed. It is exciting because zasocitinib has completed phase 3 trials, including the pivotal LATITUDE-PsO-3001 and LATITUDE-PsO-3002 trials and the head-to-head LATITUDE Atlas trial with deucravacitinib.

If we back up for a moment, deucravacitinib was already about twice as effective as apremilast using the Psoriasis Area and Severity Index (PASI) 75 metric, but it did not quite reach the PASI 90 and PASI 100 numbers that many biologic therapies can achieve. For example, in LATITUDE Atlas, 62.5% of patients on zasocitinib achieved PASI 90 at week 16, compared with only 34% of patients on deucravacitinib. For PASI 100, the numbers were 36.5% for zasocitinib vs 13.9% for deucravacitinib, with similar differences in static Physician’s Global Assessment (sPGA) of 0 responses. It is exciting that we had a first-generation TYK2 inhibitor (ie, deucravacitinib) that was already much better than our dominant oral treatment at the time (ie, apremilast), and now we have a next-generation TYK2 inhibitor that may be twice as effective as deucravacitinib, or even more so.

Moreover, in the LATITUDE Atlas trial, treatment-emergent adverse events were higher with zasocitinib at approximately 66% than with deucravacitinib at 58.7%. However, most importantly, adverse event–related discontinuations were very similar between the groups, within 0.3% of each other. It remains to be seen how this will play out in the real-world setting, but at least there is no major difference in the less favorable direction for zasocitinib compared with deucravacitinib.

Regarding the potential role of TYK2 inhibitors in managing plaque psoriasis, I typically offer patients with moderate to severe disease both injectable and oral systemic options when they are moving on from topicals, and I ask them what fits their lifestyle best. For the oral therapies, I often prescribe icotrokinra, our first-in-class oral IL-23R antagonist, due to its high efficacy and safety. This is primarily because the data for deucravacitinib and apremilast are not quite as good.

Now, with zasocitinib likely to reach the market soon and potentially offering efficacy that is similar to that of icotrokinra, I will eagerly await indirect comparison studies or special site studies to help determine which of my patients with moderate to severe plaque psoriasis might benefit more from zasocitinib than from icotrokinra.