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

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 o...

Dermatologic Disease-Directed Targeted Therapy (D3T2): The Application of Biomarker-Based Precision Medicine for the Personalized Treatment of Skin Conditions—Precision Dermatology

“…A study of 242 psoriasis patients was performed; 118 patients were treated with an IL-23 inhibitor, 79 patients were treated with an IL-17 inhibitor, and 35 patients were treated with a TNF-alpha inhibitor. The positive predictive values for IL-23 inhibitors, IL-17 inhibitors, and TNF-alpha inhibitors were 93.1%, 92.3%, and 85.7%, respectively (in contrast to the response rates of about 66% to 86% to IL-23 inhibitors; 60-70% to IL-17 inhibitors, and 25-60% to TNF-alpha inhibitors seen in patients; hence, precision dermatology based on a machine-learning-based test that evaluates baseline mRNA biomarkers can be used to select the biologic drug therapy to which a psoriasis patient is most likely to respond [20,[22][23][24][25][26]. Cost savings may be realized by giving the right drugs to the right patient at the right time: the sine qua non of precision medicine; in psoriasis, these cost savings have been estimated to average $8492 per year when transcriptomics is used to predict responders [21].…”

Predicting the outcome of psoriasis treatment

“…Protagonists of what is possible with the translation of this approach into clinical practice envisage being able to assess a patient alongside their molecular screen with biochemical and genetic predictors that will enable personalized medicine choices to be made for optimal response, most cost-effective treatment pathways and avoiding harms. 4 In this issue of the BJD, Corbett et al 2 present a comprehensive scoping review of the biomarker literature aimed at improving outcomes by predicting the effectiveness and safety of treatments for psoriasis. It is broad, including 71 studies and covering 17 different treatments, mostly biological therapies.…”

“…The authors have mapped the biomarkers onto the known pathways of importance for psoriasis including antigen processing and presentation (HLA-C*06:02), T-helper 17 cell differentiation [interleukin (IL)1B] and immune response (IL12B), and regulation of nuclear factor-jB activity (CARD14, IL17RA). 2 Their critical appraisal of these studies showed that much of the evidence base was of poor quality, with methodological and reporting limitations that excluded many studies. This has led to important recommendations for future research which in turn should ensure more effective biomarker research, going forward.…”

“…Those biomarkers to take forward are clearer from the 'catalogue' presented by Corbett et al 2 To be useful, they will need to demonstrate strong association with the desired outcome and specificity, applying similar predictive testing to those applied to diagnostic tests. The complexity of psoriasis pathogenesis, its multiple pathways and the treatment modalities involved ensure that this will require much more work.…”

“…documented in atopic dermatitis, as Staphylococcus aureus overgrowth is a predominant driver of disease flares. 2 Given that patients with congenital ichthyoses exhibit epidermal barrier defects, have altered antimicrobial peptide expression and increased risk of infections, it is likely that microbial dysbiosis exists in these patients too, but the dysbiosis across the spectrum of congenital ichthyosis was undefined, until now.…”