<p>Despite the robust efficacy of injectable biologic treatments for plaque psoriasis, some patients still prefer oral treatment options. Historically, oral therapies have not had quite the same efficacy and tolerability as our advanced biologics, but there are now multiple emerging oral options that have the potential to change the treatment landscape in plaque psoriasis. These were discussed at the <strong>2025 </strong><strong>Fall Clinical Dermatology Conference</strong>.</p> <p><br></p> <p><em>Following these presentations, featured expert Eingun James Song, MD, FAAD, was interviewed by</em> Conference Reporter<em> Associate Editor-in-Chief Christopher Ontiveros, PhD. Clinical perspectives from Dr Song on these findings are presented here.</em></p>

Emerging data show that even with the major advances in biologic therapy for plaque psoriasis, many patients remain reluctant to start an injectable and instead express a strong preference for oral options. Much of this seems driven by the stigma surrounding injections. Patients often associate needles with more dangerous medications or assume that requiring an injection signals that their disease is severe.

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At the 2025 Fall Clinical Dermatology Conference, Linda Stein Gold, MD, and colleagues presented the US findings from ENCOMPASS, a large, global, cross-sectional survey. The analysis included interviews with 400 adults with plaque psoriasis and 200 US health care providers. Among patients eligible for systemic therapy, more than half expressed a preference for an oral option, while only 15% favored an injectable. Even more striking, over 90% of patients currently on an injectable said that they would switch to an oral therapy if it offered comparable efficacy and a favorable safety profile. These results underscore a clear and ongoing patient preference for oral treatments.

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When providers take the time to explain the targeted mechanism of biologic injections—why these therapies work best when injected rather than swallowed and how infrequent dosing can actually reduce treatment burden—it can allay some patient hesitation. Still, if patients are unable to feel comfortable with injections, they will naturally continue to gravitate toward oral options. The challenge is that our current oral therapies simply do not match the efficacy or tolerability of the newest injectable biologics. In many cases, choosing an oral therapy still requires conceding some degree of efficacy.

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Beyond needle phobia, there are practical situations in which starting with an oral therapy is the more sensible option. Some patients have social or environmental barriers such as living or working in settings where the proper storage of a biologic is challenging. In addition, for patients with limited body surface area involvement but with involvement in high-impact areas such as the scalp, palms, soles, or genitals, an oral agent can be an entirely appropriate and effective choice.

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There are 3 oral treatments currently in development (ie, icotrokinra, zasocitinib, and envudeucitinib) that have the potential to deliver significantly better efficacy and tolerability than the oral options available today.

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Icotrokinra is a first-in-class oral peptide that blocks the IL-23R rather than the cytokine itself, as with our current biologics. It is now in late-stage development, and 4 phase 3 studies in moderate to severe plaque psoriasis were presented at this year’s Fall Clinical Dermatology Conference. These included ICONIC-LEAD (icotrokinra vs placebo), ICONIC-ADVANCE 1 and 2 (icotrokinra vs deucravacitinib), and ICONIC-TOTAL (icotrokinra vs placebo in plaque psoriasis involving high-impact sites). All 4 trials met their primary efficacy end points.

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A new generation of TYK2 inhibitors is also emerging, aiming to build on the strengths of deucravacitinib. Two agents are currently in development. The first, zasocitinib, was engineered to achieve a tighter and more selective binding of the TYK2 JH2 pseudokinase domain, further distancing itself from the JH1 catalytic site shared by JAK1, JAK2, and JAK3. This improved JH2 selectivity results in a more efficient blockade of IL-23 signaling, as evidenced by the more rapid and deeper response that was seen in its phase 2 trial.

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Envudeucitinib is the second next-generation TYK2 inhibitor in development. Like other allosteric TYK2 agents, it binds selectively to the regulatory JH2 pseudokinase domain, but its deuterated structure confers greater metabolic stability. This reduces the formation of reactive metabolites, lowering the potential for off-target toxicity and improving overall pharmacokinetics. Its enhanced binding affinity and selectivity for the JH2 domain translates into more sustained TYK2 inhibition and a deeper suppression of IL-23–dependent signaling, consistent with the favorable IC₉₀ data and clinical responses observed in phase 2 studies.

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If the emerging data continue to be confirmed, we may soon have 3 oral agents capable of functioning as true first-line options for patients with moderate to severe plaque psoriasis.