Potential Blood Biomarkers Predicting Treatment Response in Psoriasis: A Systematic Review and Meta-Analysis

Background/Objectives: Psoriasis is a chronic immune-mediated inflammatory disease primarily driven by the interleukin (IL)-23/T helper 17 (Th17) pathway. Despite multiple systemic therapies, treatment response varies considerably, and many patients require sequential switching. We aimed to evaluate circulating blood-derived biomarkers associated with response to systemic psoriasis therapies. Methods: MEDLINE and Web of Science were searched on 8 August 2025, following PRISMA guidance. The protocol was registered in PROSPERO (CRD420251129182). Eligible studies were original English- or Spanish-language studies published within the previous 10 years that evaluated circulating blood-derived biomarkers associated with cutaneous response to approved systemic psoriasis therapies in patients with psoriasis, with or without psoriatic arthritis. Genetic predictors, therapeutic drug monitoring studies, reviews, editorials, letters, conference abstracts, case reports, and non-original publications were excluded. Risk of bias was assessed using QUIPS and PROBAST. Quantitative synthesis included standardized mean difference meta-analysis and exploratory pooled p-value analysis. Results: Twenty-six studies were included. Most evaluated biologic therapies targeting TNF, IL-17, or IL-23; fewer assessed apremilast or methotrexate. Response definitions and follow-up varied across studies. Most studies showed moderate to high risk of bias, mainly due to small sample sizes, exploratory or post hoc analyses, heterogeneous treatment groups, limited confounding adjustment, multiple testing, and lack of external validation. Random-effects meta-analysis of baseline cytokines from two studies, including 71 patients per biomarker, showed no statistically significant differences between responders and non-responders for IL-17A, TNF-α, IL-6, IL-12, or IL-23. Exploratory pooled p-value analyses showed recurrent signals for downstream IL-23/Th17 biomarkers, particularly β-defensin-2 (BD-2; z = 4.63, p < 0.001), IL-17A (z = 3.27, p = 0.001), and IL-17F (z = 2.92, p = 0.003). Conclusions: Downstream IL-23/Th17 biomarkers, particularly BD-2 and IL-17 isoforms, showed recurrent exploratory associations with systemic treatment response. However, these findings should not be interpreted as evidence of superior predictive performance over upstream biomarkers, and no soluble circulating biomarker is currently ready for routine treatment selection.