Biomarkers of Systemic Treatment Response in People With Psoriasis

A Scoping Review

Mark Corbett; Ravi Ramessur; David Marshall; Marcio L. Acencio; Marek Ostaszewski; Ines A. Barbosa; Nick Dand; Paola Di Meglio; Salma Haddad; Andreas H.M. Jensen; Witte Koopmann; Satveer K. Mahil; Seher Rahmatulla; Joe Rastrick; Jake Saklatvala; Stephan Weidinger; Kath Wright; Kilian Eyerich; Jonathan N. Barker; Matladi Ndlovu; Curdin Conrad; Lone Skov; Catherine H. Smith

Disclosures

The British Journal of Dermatology. 2022;187(4):494-506. 

In This Article

Abstract and Introduction

Abstract

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 patients with psoriasis (any age, n ≥ 50) reporting biomarkers associated with systemic treatment response. The main outcomes were any measure of systemic treatment efficacy or safety. Data were 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 multistakeholder group using a majority voting consensus exercise and mapped to relevant cellular and molecular pathways.

Results: Of 71 included studies (67 studying effectiveness outcomes and eight safety outcomes; four studied both), most reported genomic or proteomic biomarkers associated with response to biologics (48 studies). Methodological or reporting limitations frequently compromised the interpretation of findings, including inadequate control for key covariates, lack of adjustment for multiple testing, and selective outcome reporting. We identified candidate biomarkers of efficacy to tumour necrosis factor inhibitors [variation in CARD14, CDKAL1, IL1B, IL12B and IL17RA loci, and lipopolysaccharide-induced phosphorylation of nuclear factor (NF)-κB 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, T helper (Th)17 cell differentiation, positive regulation of NF-κB, 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. The candidate biomarkers identified require further evaluation in methodologically robust studies to establish potential clinical utility. Future studies should aim to address the common methodological limitations highlighted in this review to expedite discovery and validation of biomarkers for clinical use.

Introduction

Psoriasis is a common chronic inflammatory disease, estimated to affect at least 60 million individuals globally,[1,2] and causes major impact on quality of life. Disease severity, particularly with respect to body surface area involvement, often dictates the therapeutic approach. Topical agents are generally used for localized disease, and phototherapy or systemic agents for extensive disease and/or where there is significant involvement of high-need sites or associated psoriatic arthritis. The advent of (now increasingly) powerful biologic therapies means that moderate-to-severe disease can be very effectively controlled in many.[3] However, variation in response, loss of benefit over time, toxicity, practical issues and high drug costs are all important barriers to effective management of the population as a whole.[4]

Pre-emptive identification of individuals with a higher likelihood of a safe and effective response to any selected treatment would enable targeted therapeutic selection, improved patient outcomes and more cost-effective healthcare. Biomarkers are critical to enabling this 'personalized medicine' agenda (not just in psoriasis), and have been defined (broadly) by the Food and Drug Administration and National Institutes of Health as characteristics that are measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions.[5]

Across medicine, including psoriasis, advances in omics technologies and bioinformatic approaches have unravelled biomarkers from different molecular levels that have been shown to associate with clinically relevant outcomes in several disease settings.[6] These technologies have driven a radical paradigm shift from analysis of single biomarkers to high-throughput screens profiling assays in heterogeneous datasets. Efforts in psoriasis have been underpinned by major investment and collaboration.[7,8] In this context, collating up-to-date, accessible information on the status of biomarker discovery and validation is essential to avoid research waste and redundancy, and, crucially, expedite translation of the biomarker discovery pipeline into clinical practice.

The overall aim of this review is therefore to scope, collate and catalogue research investigating biomarkers of systemic treatment response in psoriasis. The specific aims are to (i) identify and catalogue studies relating to biomarkers of systemic treatment response in psoriasis as defined by efficacy and/or safety outcomes, (ii) select and functionally map biomarkers for which there is some evidence for potential predictive value, and (iii) evaluate study quality and highlight limitations to inform future biomarker research.

processing....