Objective: To evaluate the relative cost-effectiveness of tildrakizumab and other biologic and targeted systemic treatments compared with a mix of topical therapies, phototherapies, and other conventional systemic therapies as first-line treatment for moderate-to-severe plaque psoriasis from a United States payer's perspective. Methods: A Markov model consisting of health states based on Psoriasis Area Severity Index (PASI) response rate categories and death was developed. The probabilities of

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... chieving PASI responses were derived from a network meta-analysis based on published efficacy data. Health care costs and effectiveness measured in quality-adjusted life-years (QALYs) were estimated. Incremental costs per QALY gained of each biologic/targeted first-line treatment versus a mix of conventional treatments were compared to provide relative cost-effectiveness among biologic and targeted first-line treatments. Results: Over 10 years, the incremental cost per QALY gained compared with a mix of topical therapies, phototherapies, and other oral systemic therapies was lowest for brodalumab, infliximab, apremilast, and tildrakizumab, followed by secukinumab, ixekizumab, guselkumab, adalimumab, ustekinumab, and etanercept. The position of tildrakizumab relative to the other treatments remained the same across multiple scenarios. Conclusions: Tildrakizumab is among the most cost-effective first-line therapies for moderate-to-severe plaque psoriasis and is more cost-effective than secukinumab, ixekizumab, guselkumab, adalimumab, ustekinumab, and etanercept.