Comparative efficacy and safety of IL-23 p19 monoclonal antibodies for plaque psoriasis: a bayesian network meta-analysis of randomized controlled trials.

OBJECTIVE: To compare the efficacy and safety of IL-23 p19 monoclonal antibodies for moderate-to-severe plaque psoriasis. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to 21 February 2026. We included randomized controlled trials of guselkumab, risankizumab, tildrakizumab, or mirikizumab. Efficacy outcomes were PASI75, PASI90, PASI100, and IGA/PGA/sPGA 0/1; safety outcomes were overall adverse events (AEs) and serious adverse events (SAEs). Risk of bias was assessed using RoB 2. A Bayesian network meta-analysis generated odds ratios (ORs) and 95% credible intervals (CrIs), with SUCRA, transitivity, heterogeneity, leave-one-out, and publication-bias assessments. RESULTS: Thirteen articles comprising 15 RCTs or independent study units were included. Networks were largely placebo-centred, with limited direct active-agent comparisons. Versus placebo, all four agents significantly improved PASI75, PASI100, and IGA/PGA/sPGA 0/1. For PASI90, risankizumab, guselkumab, and mirikizumab were superior to placebo, whereas the tildrakizumab CrI crossed the null. PASI75 ORs versus placebo were 124.04 for risankizumab, 105.41 for guselkumab, 72.36 for mirikizumab, and 24.05 for tildrakizumab. Corresponding ORs for IGA/PGA/sPGA 0/1 were 89.73, 68.84, 52.82, and 21.46. Most comparisons among risankizumab, guselkumab, and mirikizumab were not statistically significant; tildrakizumab showed lower PASI75 and IGA/PGA/sPGA 0/1 responses. SUCRA generally ranked risankizumab highest or near highest, followed by guselkumab and mirikizumab, with tildrakizumab lower. No agent differed significantly from placebo in AE or SAE risk. Sensitivity analyses supported stable efficacy findings, and Egger's tests found no clear publication bias. CONCLUSION: IL-23 p19 antibodies improve skin-clearance outcomes without a clear increase in overall AE or SAE risk. Risankizumab had the most favourable ranking probability, but limited direct evidence and overlapping CrIs preclude definitive superiority claims. Biologic selection should also consider prior treatment, comorbidities, dosing, access, and patient preference. Head-to-head trials and long-term real-world studies are needed. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO, identifier CRD420261382915.