Efficacy and safety of icotrokinra for plaque psoriasis: a systematic review and meta-analysis

BACKGROUND: In biologic therapies targeting interleukin (IL)-23 for plaque psoriasis, parenteral administration can limit treatment adherence and quality of life. Icotrokinra is a first-in-class oral peptide that selectively antagonizes the IL-23 receptor and has shown promising efficacy in phase II and phase III trials. However, a comprehensive synthesis of efficacy and safety across these trials is currently lacking. OBJECTIVES: To evaluate the efficacy and safety of icotrokinra in adolescents (12-17 years) and adults (≥ 18 years) with moderate-to-severe plaque psoriasis. METHODS: PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched on 8 December 2025, with reference lists hand-searched for additional studies. Randomized controlled trials enrolling the target population were included if they compared icotrokinra with placebo and reported efficacy or safety outcomes. RESULTS: Five randomized controlled trials (one phase II and four phase III), comprising four reports, met the inclusion criteria. Icotrokinra significantly increased the likelihood of achieving an Investigator's Global Assessment score of 0 or 1 at week 16 compared with placebo (risk ratio 7.27, 95% confidence interval 5.80-9.11), with no heterogeneity (I2 = 0%). High-level skin clearance, represented by ≥ 90% improvement in Psoriasis Area and Severity Index, was also significantly improved (risk ratio 13.8, 95% confidence interval 7.21-26.5). Rates of treatment-emergent and serious adverse events were comparable between icotrokinra and placebo, with no new safety signals identified over the 16-week trial period. CONCLUSIONS: Icotrokinra has shown short-term efficacy and a favourable safety profile in patients with moderate-to-severe plaque psoriasis. Combining biologic-level efficacy with ease of administration, icotrokinra may represent an important advance in psoriasis therapy.