对通常用于治疗牛皮癣的全身治疗的反应各不相同。准确预测有效性和安全性的生物标志物将使有针对性的治疗选择成为可能。改善患者预后和更具成本效益的医疗保健。
进行范围审查,以确定和编目用于转化研究社区的银屑病全身治疗反应的候选生物标志物。
对中央的系统搜索,Embase,LILACS和MEDLINE是在1990年至2021年12月之间发表的相关文章中进行的。合格标准是涉及牛皮癣患者的研究(任何年龄,n≥50)报告与全身治疗反应相关的生物标志物。主要结果是任何衡量全身治疗效果或安全性的指标。数据由一个审阅者提取,并由第二个审阅者检查;正式评估符合最低质量标准(使用控制混杂因素的方法)的研究的偏倚。由专家多利益相关者小组使用多数投票共识练习来鉴定候选生物标志物,并将其映射到相关的细胞和分子途径。
在纳入的71项研究中(67项研究有效性结果和8项安全性结果;4项研究均有),大多数报道的与生物制剂反应相关的基因组或蛋白质组生物标志物(48项研究)。方法或报告的局限性经常影响对调查结果的解释,包括对关键协变量的控制不足,缺乏对多重测试的调整,和选择性结果报告。我们确定了对肿瘤坏死因子抑制剂有效的候选生物标志物[CARD14,CDKAL1,IL1B,IL12B和IL17RA位点,和脂多糖诱导的2型树突状细胞中核因子(NF)-κB的磷酸化]和ustekinumab(HLA-C*06:02和IL1B基因座的变异)。没有足够的证据支持临床使用,没有进一步的验证研究。候选生物标志物被发现参与银屑病发病机制的免疫细胞串扰,最值得注意的是抗原呈递,T辅助(Th)17细胞分化,NF-κB的正调节,和Th17细胞激活。
这个全面的目录为研究人员提供了关键资源,并揭示了纳入研究的各种生物标志物类型和结果。所鉴定的候选生物标志物需要在方法上稳健的研究中进一步评估以建立潜在的临床效用。未来的研究应旨在解决本综述中强调的常见方法学局限性,以加快发现和验证临床使用的生物标志物。关于这个主题已经知道什么?对通常用于治疗牛皮癣的全身治疗的反应各不相同。准确预测有效性和安全性的生物标志物将使有针对性的治疗选择成为可能。改善患者预后和更具成本效益的医疗保健。这项研究补充了什么?这篇综述提供了银屑病全身治疗反应的生物标志物的综合目录。在纳入的研究中发现了各种各样的生物标志物类型和结果,作为转化研究社区的关键资源。
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.
To perform a scoping
review to identify and catalogue candidate biomarkers of systemic treatment response in psoriasis for the translational research community.
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.
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.
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.