Ustekinumab for the treatment of psoriasis: a well-established therapy primed for resurgence

INTRODUCTION: Ustekinumab has been an approved biologic therapy for moderate-to-severe psoriasis for over 16 years. With the emergence of newer IL-17 and IL-23 inhibitors, its use was largely supplanted by these more effective treatments. With the introduction of biosimilars, ustekinumab's potential role in the current treatment landscape warrants reassessment, as insurers may encourage first line use again. AREAS COVERED: This review summarizes the mechanism of action, clinical trial data, real-world evidence, and biosimilar development of ustekinumab in psoriasis. A literature search was conducted using PubMed and relevant clinical trial databases, focusing on studies published from 2008 to 2025. Key trials, including PHOENIX, ACCEPT, CLEAR, and UltIMMa, as well as registry data and recent observational studies, are discussed to evaluate efficacy, safety, and comparative effectiveness. EXPERT OPINION: While newer biologics are more effective, ustekinumab remains a good option due to its dosing convenience, established safety profile, efficacy for the common psoriatic arthritis comorbidity, and lower cost afforded by ustekinumab biosimilars. In health systems that prioritize exclusively efficacy and safety, ustekinumab may play little role in psoriasis management. However, in systems that prioritize lower cost treatment, biosimilar adalimumab and ustekinumab could be preferred first line treatments, and of these two, ustekinumab may be preferred over adalimumab because of greater efficacy, better safety, and fewer injections.