Where Oral Peptide Therapy Fits Alongside Biologics in Plaque Psoriasis

In this episode, ‘How Icotrokinra Fits Alongside Biologics in Plaque Psoriasis,’ the panelists, both practicing in dermatology, explore where the therapy's mechanism of action fits within the broader treatment landscape.

The discussion turns to mechanism of action as Andrew Mastro, MS, PA-C, asks Alexa Hetzel, MS, PA-C, where icotrokinra sits conceptually relative to the biologic classes that have anchored psoriasis treatment. Hetzel describes the available therapies as a cone, or a food pyramid, narrowing from broad to specific. TNF inhibitors sit at the wide base, developed before the field fully understood where they fit within the inflammatory cascade of psoriasis. IL-17 inhibitors occupy a tighter band, reflecting a more specific target, and IL-23 inhibitors sit at the narrowest, most specific point in that same cascade.

What distinguished the earlier oral options, Hetzel explains, is that agents like PDE4 and TYK2 inhibitors sat outside that cone entirely. Their mechanisms did not map onto the same inflammatory pathway clinicians had grown accustomed to with the injectable biologics, which added a layer of new learning for prescribers. Icotrokinra, by contrast, is itself an IL-23 inhibitor, placing it inside the same cornerstone pathway as the injectable IL-23 class clinicians already understand and trust.

The distinction Hetzel draws is in the binding target rather than the pathway itself. Icotrokinra does not bind the IL-23 cytokine directly, as the injectable IL-23 inhibitors do; it binds the IL-23 receptor, which she notes lives specifically on inflamed tissue. She frames this as a small conceptual adjustment rather than an entirely new mechanism to learn, which lowers the educational barrier to adoption compared with the earlier oral classes.

Understanding that receptor-level mechanism, Hetzel adds, is part of why the efficacy data has made sense to clinicians relatively quickly, since it builds on a pathway most dermatology providers already treat as a cornerstone of their practice rather than asking them to master an unfamiliar inflammatory cascade from scratch. Where the earlier oral agents required providers to learn a largely separate safety and mechanism story before they could confidently counsel patients, an IL-23-targeted oral peptide lets clinicians lean on years of accumulated comfort with that class. For Hetzel, that familiarity is a meaningful part of icotrokinra's appeal, not just its clinical trial results.

In the next episode, ‘Choosing the Right Plaque Psoriasis Patient for Icotrokinra,’ Mastro and Hetzel walk through real-world patient cases that help identify who is best suited for the therapy.