Efficacy and Safety of Oral Icotrokinra in Moderate-to-Severe Plaque Psoriasis: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis.

Oral therapies for moderate-to-severe plaque psoriasis are limited by modest efficacy or safety concerns. Icotrokinra is a novel oral interleukin-23 receptor antagonist peptide that has shown promising efficacy in randomized trials. This study aimed to systematically evaluate the efficacy and safety of icotrokinra in patients with moderate-to-severe plaque psoriasis. A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing icotrokinra 200 mg once daily with placebo was conducted in accordance with PRISMA 2020 guidelines. The primary outcome was achievement of a ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75) at Week 16. Random-effects models were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), and trial sequential analysis was performed. Five RCTs, including 1951 participants, were analyzed. Icotrokinra 200 mg once daily significantly increased PASI 75 response rates compared with placebo at Week 4 (15% vs. 2%; OR = 6.57, 95% CI 3.66-11.81; p < 0.0001) and Week 16 (73% vs. 11%; OR = 22.03, 95% CI 16.13-30.10; p < 0.0001). Higher clearance thresholds also favored icotrokinra, including PASI 90 (54% vs. 4%; OR = 28.24) and PASI 100 (30% vs. 1%; OR = 45.86). The incidence of adverse events, serious adverse events, and infections did not differ significantly between groups. Icotrokinra is an effective and well-tolerated oral treatment for moderate-to-severe plaque psoriasis, offering rapid and sustained clinical benefit with a safety profile comparable to placebo. It represents a promising oral option bridging the gap between existing oral therapies and biologics.