Selective TYK2 inhibition for the treatment of psoriatic disease
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During the PsOPsA Hub Steering Committee Meeting on July 16, 2025, Paolo Gisondi, University Hospital of Verona, Verona, IT, chaired a discussion on selective TYK2 inhibition for the treatment of psoriatic disease. The discussion also featured Ulrich Mrowietz, Peter Nash, and Yukari Okubo.
Discussion
• The clinical utility of TYK2 inhibitors is often questioned, given their moderate efficacy (PASI 90 response rates less than 50%), and relatively higher incidence of AEs (e.g. folliculitis, nasopharyngitis) and infections, especially when compared with IL-23 p19 inhibitors.
• Oral administration of deucravacitinib and zasocitinib offers practical advantages, though patient preferences vary by region. Oral agents are favored in Japan and Australia for convenience, easier storage, or for patients recovering from AEs associated with biologics (especially with tumor necrosis factor inhibitors), while in Germany, injectables are preferred for their greater efficacy, less frequent dosing, and lower psychological burden.
• In Australia, oral agents remain integral to PsA management, particularly as bridging therapies before biologics. Deucravacitinib is generally well-tolerated in patients with mild-to-moderate PsA and is often used off-label in combination with traditional biologics for treatment-refractory cases.
• In Japan, apremilast is typically prescribed first due to its lower cost, with TYK2 inhibitors considered upon failure. For moderate-to-severe PsO, earlier initiation of TYK2 inhibitors is being explored, while biologics remain the preferred option in PsA.
• Real-world data from Germany indicate the highest drug survival with IL-23 p19 inhibitors, followed by IL-17 inhibitors and adalimumab. In contrast, oral treatments including apremilast and deucravacitinib show lower drug survival, due to factors such as limited efficacy and AEs, meaning they are less favorable from both clinical and economic perspectives.
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