Efficacy and Safety of Icotrokinra for Plaque Psoriasis: A Systematic Review and Meta-analysis

Abstract Background In biologic therapies targeting interleukin-23 (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 2 and phase 3 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 years) and adults (>18) with moderate-to-severe plaque psoriasis. Methods PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched on December 8th, 2025, with reference lists hand-searched for addition studies. Randomized controlled trials enrolling the target population which compared icotrokinra with placebo and reported efficacy or safety outcomes were included. Results Five randomized controlled trials (one phase 2 and four phase 3), comprising 4 reports, met inclusion criteria. Icotrokinra significantly increased the likelihood of achieving IGA 0/1 at week 16 compared with placebo (RR, 7.27; 95% CI, 5.80–9.11), with no heterogeneity (I2=0%). High-level skin clearance, represented by Psoriasis Area and Severity Index 90 was also significantly improved (RR, 13.82; 95% CI, 7.21-26.51). 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. Conclusion Icotrokinra has shown short-term efficacy and a favorable 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.