Biomarkers of systemic treatment response in people with psoriasis: a scoping review

Background Responses to the systemic treatments commonly used to treat psoriasis vary. Biomarkers that accurately predict effectiveness and safety would enable targeted treatment selection, improved patient outcomes and more cost-effective healthcare. Objectives To perform a scoping review to identify and catalogue candidate biomarkers of systemic treatment response in psoriasis for the translational research community. Methods A systematic search of CENTRAL, Embase, LILACS, and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving the psoriasis population (any age, n≥50) reporting biomarkers associated with systemic treatment response. The main outcomes were any measure of systemic treatment efficacy or safety. Data was extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multi-stakeholder group using a majority voting consensus exercise and mapped to relevant cellular and molecular pathways. Results Of 71 included studies (n=64 effectiveness outcomes and n=8 safety outcomes), most reported genomic or proteomic biomarkers associated with response to biologics (n=48 studies). Methodological or reporting limitations frequently compromised the interpretation of findings, including inadequate control for key prognostic factors, lack of adjustment for multiple testing and selective outcome reporting. We identified candidate biomarkers of efficacy to TNF inhibitors (variation in CARD14, CDKAL1, IL1B, IL12B, IL17RA loci and LPS-induced phosphorylation of NF-kB in Type 2 dendritic cells) and ustekinumab (HLA-C*06:02 and variation in an IL1B locus). None were supported by sufficient evidence for clinical use without further validation studies. Candidate biomarkers were found to be involved in the immune cellular crosstalk implicated in psoriasis pathogenesis, most notably antigen presentation, Th17 cell differentiation, positive regulation of NF-kB and Th17 cell activation. Conclusions This comprehensive catalogue provides a key resource for researchers and reveals a diverse range of biomarker types and outcomes in the included studies. Candidate biomarkers identified require further evaluation in methodologically robust studies to establish potential clinical utility. Future studies should aim to address common methodological limitations highlighted in this review to expedite discovery and validation of biomarkers for clinical use.