The Role of TYK2 Inhibitors in the Pathogenesis and Treatment of Psoriasis.

BACKGROUND: Psoriasis is a chronic, inflammatory condition that has a substantial effect on quality of life. Tyrosine kinase 2 (TYK2) inhibitors have emerged as a promising class of agents for treating psoriasis. OBJECTIVE: To summarize the current evidence on TYK2 inhibitors and their role in the management of psoriasis. METHODS: A comprehensive literature search was conducted using a combination of the keywords "psoriasis," "tyrosine kinase," "pathogenesis," "mechanism of action," and "emerging therapies." The authors reviewed all studies and included those that addressed the topic of the review. RESULTS: TYK2 plays an integral role in the pathogenesis of psoriasis. Targeting TYK2 as a therapeutic pathway has led to significant improvement in disease severity and quality of life. Deucravacitinib was the first TYK2 inhibitor approved by the Unitefor moderate-to-severe plaque psoriasis. Zasocitinib and envudeucitinib are 2 agents currently undergoing late-stage clinical trials for psoriasis. The mechanism of action for these therapies is similar, targeting the JH2 pseudokinase domain of TYK2, but each has distinct features that differentiate their effectiveness and safety. Several other TYK2 inhibitors are in earlier development, including D-2570, ICP-488, AC-201, and TLL-018. LIMITATIONS: This review is limited by the information available in the published literature. In addition, comparisons between studies are limited as varying methodologies were used. CONCLUSION: TYK2 inhibition represents a significant advancement for the treatment of psoriasis. Continued research will enable optimization of these agents in managing psoriasis and related immune-mediated diseases.