PDF(Pubmed)
Abstract：
Background/Objectives: Psoriasis is a chronic, inflammatory, immuno-mediated cutaneous disease characterized by a prominent TNFα-IL23/IL17 immune axis. In recent years, targeted therapies have become standard practice for managing moderate-to-severe psoriasis and have demonstrated efficacy. At the same time, identifying factors associated with the success or failure of TNFα inhibitor therapy remains one of the most difficult aspects in psoriasis treatment. Methods: A clinical, non-randomized study was conducted to evaluate the impact of TNFα inhibitors on the plasma cytokine profiles in patients with moderate-to-severe psoriasis vulgaris (ICD-10 code L40.0). The patients were treated with either etanercept, adalimumab, or infliximab for 16 weeks. Plasma cytokine profiles were assessed using a BioPlex200 System. Results: By the 16th week of therapy, a positive treatment response (PASI ≥ 75) was observed in 51 patients (63%), while 30 patients (37%) showed no response (PASI ≤ 50). When using etanercept, a positive effect was observed in 11 patients (41%), in 14 patients (52%) using adalimumab, and in 26 patients (96%) using infliximab. Analysis of the baseline cytokine levels revealed no differences between the \"positive effect\" and \"no effect\" groups, except for IL20, which was 2.61 times higher in the \"positive effect\" group compared to the \"no effect\" group, suggesting its potential predictive role in the effectiveness of therapy with TNFα inhibitors. Treatment led to a decrease in IL17F, IL31, sCD40L, and VEGF for all patients, and in IL20 for the \"positive effect\" group. The increase in ICAM1 in the \"no effect\" group suggests the possible retention of active migration and the fixation of T cells in the affected skin in these patients. No significant difference in cytokine levels was observed when categorizing patients into subgroups based on the effectiveness of therapy with etanercept, infliximab, and adalimumab; only a pre- and post-treatment difference in the whole cohort was noted. A random forest model showed the importance of VEGF, sCD40L, and ICAM1. Conclusions: The baseline levels of VEGF, sCD40L, and ICAM1, as well as IL20, could serve as potential predictors of treatment effectiveness using TNFa inhibitors. However, this hypothesis requires confirmation with a larger patient population.
摘要：
背景/目的：牛皮癣是一种慢性，炎症，以显著的TNFα-IL23/IL17免疫轴为特征的免疫介导的皮肤病。近年来,靶向治疗已成为治疗中度至重度银屑病的标准方法,并已证明疗效.同时,确定与TNFα抑制剂治疗成败相关的因素仍然是银屑病治疗中最困难的方面之一.方法：临床，我们进行了非随机研究,以评估TNFα抑制剂对中度至重度寻常型银屑病患者血浆细胞因子谱的影响(ICD-10代码L40.0).患者接受了依那西普治疗，阿达木单抗,或英夫利昔单抗治疗16周。使用BioPlex200系统评估血浆细胞因子谱。结果：到第16周的治疗，在51例患者（63%）中观察到积极的治疗反应（PASI≥75），30例患者（37%）无反应（PASI≤50）。当使用依那西普时，在11例患者（41%）中观察到积极效果，14例患者（52%）使用阿达木单抗，26例患者（96%）使用英夫利昔单抗。对基线细胞因子水平的分析显示，“正效应”和“无效应”组之间没有差异，除IL20外，“正效应”组比“无效应”组高2.61倍，提示其在TNFα抑制剂治疗有效性中的潜在预测作用。治疗导致IL17F减少，IL31,sCD40L,所有患者的VEGF，和IL20中的“正效应”组。“无作用”组中ICAM1的增加表明，这些患者的受影响皮肤中可能保留了主动迁移和T细胞的固定。根据依那西普治疗的有效性将患者分为亚组时，未观察到细胞因子水平的显着差异。英夫利昔单抗,和阿达木单抗;仅注意到整个队列中治疗前后的差异.随机森林模型显示了VEGF的重要性，sCD40L,和ICAM1。结论:VEGF的基线水平,sCD40L,和ICAM1以及IL20可以作为使用TNFa抑制剂治疗有效性的潜在预测因子.然而,这一假设需要在更大的患者人群中得到证实.
