外周血炎症指标对生物制剂治疗斑块型银屑病疗效的动态评估研究

Correlation between peripheral blood inflammatory markers and efficacy of biologic agents in treating plaque psoriasis

  • 摘要:
    背景 外周血炎症指标反映了机体在炎症反应与免疫失衡中的内环境变化,但其能否作为生物制剂治疗银屑病疗效及预后的标志物有待进一步探讨。
    目的 分析中重度斑块型银屑病患者治疗前外周血炎症指标与银屑病严重程度的相关性及其在预测英夫利昔单抗、司库奇尤单抗治疗效果方面的潜力。
    方法 回顾性分析本单位既往开展的两项随机、双盲、对照Ⅲ期临床试验数据,研究对象为2016年10月— 2017年10月以及2019年1月— 2021年9月接受生物制剂治疗的中重度斑块型银屑病患者,分为英夫利昔单抗组、司库奇尤单抗组和安慰剂(0.9%氯化钠注射液)对照组。分析治疗前、治疗4周、治疗12周中性粒细胞/淋巴细胞比值、全身炎症综合指数(aggregate index of systemic inflammation,AISI)、全身免疫炎症指数(systemic inflammatory response index,SIRI)等外周血炎症指标的变化,以及这些指标与银屑病面积和严重程度指数(psoriasis area and severity index,PASI)的相关性、与生物制剂治疗反应的相关性。
    结果 共纳入39例患者,其中英夫利昔单抗组10例,年龄30 ~ 61岁,男性9例,女性1例;司库奇尤单抗组22例,年龄20 ~ 51岁,男性19例,女性3例;对照组7例,年龄24 ~ 41岁,均为男性。相关性分析结果显示,PASI评分与SIRI、AISI呈正相关(rSIRI=0.472,PSIRI<0.05;rAISI=0.373,PAISI<0.05)。双因素重复测量方差分析结果显示,SIRI和AISI两指标在时间和组间维度上整体均有统计学差异(P<0.05)。在时间维度上,司库奇尤单抗治疗4周和12周SIRI值较治疗前分别降低0.28(95% CI:0.07 ~ 0.49)、0.38(95% CI:0.17 ~ 0.69),差异均有统计学意义(P<0.05);司库奇尤单抗治疗4周和12周AISI值较对照组分别降低91.17(95% CI:1.27 ~ 181.07)、115.06(95% CI:23.23 ~ 206.89),差异均有统计学意义(P<0.05)。在组间维度上,英夫利昔单抗治疗4周和12周SIRI值较对照组分别降低0.43(95% CI:0.01 ~ 0.84)、0.63(95% CI:0.26 ~ 1.00),差异均有统计学意义(P<0.05);英夫利昔单抗治疗4周和12周AISI值较对照组分别降低115.92(95% CI:11.45 ~ 220.39)、170.61(95% CI:62.22 ~ 279.00),差异均有统计学意义(P<0.05)。司库奇尤单抗治疗4周和12周SIRI值较对照组分别降低0.52(95% CI:0.16 ~ 0.88)、0.76(95% CI:0.44 ~ 1.09),差异均有统计学意义(P<0.05)。司库奇尤单抗治疗4周和12周AISI值较对照组分别降低137.21(95% CI:45.22 ~ 229.20)、198.03(95% CI:102.58 ~ 293.47),差异均有统计学意义(P<0.05)。
    结论 SIRI、AISI指标与治疗前斑块型银屑病的严重程度密切相关,提示这些炎症指标可作为银屑病严重程度的潜在评估工具。英夫利昔单抗和司库奇尤单抗均显著降低SIRI和AISI值,司库奇尤单抗在降低AISI方面表现更优,两者长期治疗的抗炎效果相似,可为生物制剂治疗银屑病提供参考依据。

     

    Abstract:
    Background Peripheral blood inflammatory indicators reflect systemic homeostasis during inflammatory responses and immune dysregulation, yet their potential as biomarkers for therapeutic efficacy and prognosis in psoriasis patients receiving biologics warrants further investigation.
    Objective To analyze the correlation between baseline peripheral blood inflammatory indicators and psoriasis severity in moderate-to-severe plaque psoriasis patients, and evaluate their predictive value for treatment outcomes with infliximab and secukinumab.
    Methods A retrospective analysis was conducted using data from two randomized, double-blind, controlled phase Ⅲ clinical trials at our institution. Patients with moderate-to-severe plaque psoriasis treated with biologics from October 2016 to October 2017 and January 2019 to September 2021 were categorized into three groups: infliximab group, secukinumab group and control group. Neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SIRI), and aggregate index of systemic inflammation (AISI) were analyzed at baseline, week 4, and week 12. Correlations between these indices and Psoriasis Area and Severity Index (PASI) scores, as well as their association with therapeutic responses, were evaluated.
    Results A total of 39 patients were enrolled, including 10 caes in the infliximab group (age range: 30-61 years; 9 males, 1 female), 22 cases in the secukinumab group (age range: 20-51 years; 19 males, 3 females), and 7 cases in the control group (age range: 24-41 years; all males). Correlation analysis revealed positive associations between PASI scores and SIRI (r = 0.472, P < 0.05) as well as AISI (r = 0.373, P < 0.05). Two-way repeated measures ANOVA demonstrated significant differences in both SIRI and AISI across time dimensions and between groups (P < 0.05). In the time dimension analysis, secukinumab treatment significantly reduced SIRI by 0.28 (95% CI: 0.07 - 0.49) at week 4 and 0.38 (95% CI: 0.17 - 0.69) at week 12 compared to baseline (P < 0.05), while AISI decreased by 91.17 (95% CI: 1.27 - 181.07) and 115.06 (95% CI: 23.23 - 206.89) compared with the control group at weeks 4 and 12, respectively (P < 0.05). In the intergroup comparison, Infliximab showed SIRI reduction of 0.43 (95% CI: 0.01 - 0.84) at week 4 and 0.63 (95% CI: 0.26 - 1.00) at week 12 compared with controls (P < 0.05), with AISI decreasing by 115.92 (95% CI: 11.45 - 220.39) and 170.61 (95% CI: 62.22 - 279.00) at the corresponding time points (P < 0.05); Secukinumab exhibited greater SIRI reduction of 0.52 (95% CI: 0.16 - 0.88) and 0.76 (95% CI: 0.44 - 1.09) at weeks 4 and 12 compared with controls (P < 0.05), along with AISI decrease of 137.21 (95% CI: 45.22 - 229.20) and 198.03 (95% CI: 102.58 - 293.47) at these intervals (P < 0.05).
    Conclusion The strong correlation between SIRI/AISI indexes and baseline severity of plaque psoriasis suggests their potential utility as objective biomarkers for disease severity assessment. Both infliximab and secukinumab significantly reduced SIRI and AISI values, with secukinumab demonstrating superior efficacy in AISI reduction. Notably, their comparable long-term anti-inflammatory effects provide critical evidence for optimizing biologic therapies in psoriasis management.

     

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