Biologics Versus Oral Small Molecules — Redefining the Psoriasis Treatment Hierarchy

Strober explains how the arrival of icotrakinra, a first-in-class oral IL-23 receptor blocker, has meaningfully shifted the psoriasis treatment paradigm.

The treatment of moderate to severe psoriasis has been transformed over the past decade by the development of biologic agents targeting the IL-23/IL-17 axis — a cytokine cascade now well established as central to the pathophysiology of psoriatic inflammation. Agents including risankizumab, guselkumab, bimekizumab, and ixekizumab have demonstrated the capacity to achieve deep skin clearance, with substantial proportions of patients reaching Psoriasis Area and Severity Index (PASI) 90 and PASI 100 responses in pivotal trials and real-world settings. These agents remain among the most efficacious treatments in dermatology across any indication, and their performance ceiling — in terms of both speed and depth of response — currently exceeds that of available oral alternatives. For patients in whom rapid, profound clearance is the primary goal, advanced biologics continue to define the standard of care.

That hierarchy has nonetheless been complicated by the introduction of icotrakinra, a first-in-class oral small molecule that targets the IL-23 receptor directly, blocking the downstream effects of IL-23 signaling without requiring injection. Oral agents have historically occupied a lower tier in psoriasis management — effective at mild to moderate disease burdens but unable to approach the response rates of advanced biologics. Icotrakinra challenges that positioning. Phase 3 trial data demonstrated PASI 90 response rates of approximately two-thirds of patients at week 24, a level of efficacy without precedent for an oral psoriasis therapy and one that meaningfully narrows the gap with injectable IL-23 inhibitors. Icotrakinra's once-daily oral dosing, absence of a requirement for routine laboratory monitoring, and manageable safety profile — including a label notation regarding tuberculosis screening that does not mandate testing in all patients — collectively represent a practical convenience profile that injectable biologics cannot match.

In this video discussion on psoriasis treatment selection, Bruce Strober, MD, PhD, Clinical Professor of Dermatology at Yale University School of Medicine, describes how icotrakinra's arrival has already influenced his prescribing behavior in clinical practice. Drawing on approximately 6 weeks of early real-world experience across multiple patients, Strober characterizes icotrakinra as a therapy that is straightforward to initiate, well tolerated, and capable of producing responses he describes as impressive by oral therapy standards. He positions it not as a replacement for advanced biologics but as a meaningful new option for a specific patient population — those who prefer or require oral administration and for whom the efficacy ceiling of an oral IL-23 receptor blocker is acceptable given their disease severity, lifestyle, and treatment goals. The availability of a once-daily oral agent approaching biologic-level outcomes represents, in his view, a genuine paradigm shift for dermatology — one whose full implications for prescribing patterns are still being defined.