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

Abstract

Highlights Why Was the Study Undertaken? Treatment response in psoriasis remains variable despite multiple systemic therapies, and patients often require sequential switching. This systematic review and meta-analysis was undertaken to evaluate whether circulating blood-derived biomarkers can predict response to systemic psoriasis treatments and support more personalized treatment selection. What Does This Study Add? The study identifies recurrent exploratory signals for downstream IL-23/Th17 path-way biomarkers, particularly BD-2, IL-17A, and IL-17F, while upstream IL-23 showed only a non-significant trend. BD-2 showed the largest pooled statistical signal, but these findings remain hypothesis-generating rather than validated predictors. What Are the Implications of This Study for Disease Understanding and/or Clinical Care? The findings are compatible with the hypothesis that amplified downstream pathway activity may better reflect treatment-responsive inflammation than isolated upstream cytokines. However, this interpretation remains exploratory, and no soluble circulating biomarker is currently sufficiently validated for routine treatment selection; prospective multicenter studies using standardized assays and biomarker panels are needed before clinical implementation. Abstract 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.