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

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Mark Corbett, Ravi Ramessur, David Marshall, Marcio Acencio, Marek Ostaszewski, Ines Biscaia De Andrade Barbosa, Nick Dand, Paola Di Meglio, Salma Haddad, Andreas Jensen, Witte Koopmann, Satveer Mahil, Seher Rahmatulla, Joe Rastrick, Jake Saklatvala, Stephan Weidinger, Kath Wright, Kilian Eyerich, Jonathan Barker, Matladi Ndlovu & 3 more Curdin Conrad, Lone Skov, Catherine Smith

Original languageEnglish
Pages (from-to)494-506
Number of pages13
JournalBritish Journal of Dermatology
Volume187
Issue number4
DOIs
PublishedOct 2022

Bibliographical note

Funding Information: This scoping review was supported and funded by the International Psoriasis Council (IPC) and the BIOMAP (Biomarkers in Atopic Dermatitis and Psoriasis) consortium. This study was also supported by the Psoriasis Association, UK. This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement number 821511 (BIOMAP). The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The research also received funding from the National Institute for Health and Care Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. S.K.M. is funded by a Medical Research Council Clinical Academic Research Partnership award (MR/T02383X/1). N.D. is funded by Health Data Research UK (MR/S003126/1). Funding Information: P.D.M. has received research grants from UCB and consultancy or speaker honoraria from Novartis, UCB and Janssen. S.K.M. has received departmental funding from AbbVie, Celgene, Eli Lilly, Janssen‐Cilag, Novartis, Sanofi and UCB. K.E. has received honoraria and/or research grants from AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, LEO, Lilly, Novartis, Pfizer and UCB. J.N.B. has received honoraria and/or research grants from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Janssen, LEO, Lilly, Novartis, Samsung and Sun Pharma. C.C. has received honoraria and/or research grants from AbbVie, Actelion, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, MSD, Novartis, Pfizer, Samsung and UCB. L.S. has received honoraria and/or research grants from AbbVie, Almirall, Bristol Myers Squibb, Celgene, Sanofi, UCB, Janssen, LEO Pharma, Lilly and Novartis. C.H.S. reports grants from a Medical Research Council‐funded stratified medicine consortium with multiple industry partners, grants from an Innovative Medicines Initiative (Horizon 2020)‐funded European consortium with multiple industry partners, and others from AbbVie, Novartis, Pfizer, Sanofi, Boehringer Ingelheim and SOBI, outside the submitted work; she is also chair of UK guidelines on biologic therapy in psoriasis. The remaining authors declare that they have no relevant conflicts of interest. Publisher Copyright: © 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

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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. What is already known about this topic? 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. What does this study add? This review provides a comprehensive catalogue of investigated biomarkers of systemic treatment response in psoriasis. A diverse range of biomarker types and outcomes was found in the included studies, serving as a key resource for the translational research community.

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