Background Since not all Crohn's disease (CD) patients respond adequately to ustekinumab therapy, biomarkers could aid to monitor treatment response and optimize therapeutic outcomes. Objectives To explore the dynamics of serum biomarker concentrations to monitor the response to ustekinumab treatment in CD patients. Design Retrospective, exploratory study to evaluate concentrations of serum cytokines and acute phase proteins and their relation to endoscopic remission in CD patients during ustekinumab treatment. Methods Serum concentrations of 16 proteins including cytokines and acute phase proteins were measured using the Mesoscale Discovery Platform in serum of healthy controls (n = 13), and CD patients (n = 61) at baseline (week 0), week 8 and week 24 during ustekinumab treatment. Endoscopic remission was defined as simple endoscopic score for CD (SES-CD) <3 after 6 months of therapy. Results Absolute concentrations of serum amyloid A protein (SAA; week 8), IL-6 (week 24), AGP (weeks 8 and 24), interferon (IFN)-γ (weeks 8 and 24), lipopolysaccharide binding protein (LBP; weeks 8 and 24) and IL-22 (weeks 8 and 24) were significantly lower in endoscopic remitters compared to non-responders (p-values ranging between <0.001 and <0.05). SAA (week 8) and AGP (week 24) were the biomarkers with the highest area under the ROC curve (AUROC; 0.761 and 0.760, respectively) for identifying patients in endoscopic remission, though their performance was not superior to C-reactive protein (CRP) or faecal calprotectin. AUROCs of the predictive probability of biomarker combinations showed superiority in discriminating endoscopic remitters from non-responders in comparison to single biomarker measurements, but not as compared to faecal calprotectin. Conclusion Although not superior to faecal calprotectin, measurement of AGP, SAA, LBF, IFN-γ, IL-6 and IL-22 concentrations, and combinations thereof with or without CRP and faecal calprotectin, during ustekinumab therapy might contribute to adequate monitoring of treatment response in CD patients.

中文翻译：

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评估血清细胞因子和急性期蛋白作为可能的药效生物标志物，以监测克罗恩病患者乌特克单抗治疗期间的内镜缓解情况。

背景 由于并非所有克罗恩病 (CD) 患者都对优特克单抗治疗有充分反应，生物标志物可以帮助监测治疗反应并优化治疗结果。目的 探讨血清生物标志物浓度的动态变化，以监测 CD 患者对乌特克单抗治疗的反应。设计回顾性、探索性研究，以评估优特克单抗治疗期间 CD 患者血清细胞因子和急性期蛋白的浓度及其与内镜缓解的关系。方法 使用 Mesoscale Discovery Platform 测量基线（第 0 周）、第 8 周和第 24 周时健康对照 (n = 13) 和 CD 患者 (n = 61) 血清中 16 种蛋白质（包括细胞因子和急性期蛋白）的血清浓度在优特克单抗治疗期间。内镜缓解定义为治疗 6 个月后 CD 简单内镜评分 (SES-CD) <3。结果 血清淀粉样蛋白 A 蛋白（SAA；第 8 周）、IL-6（第 24 周）、AGP（第 8 周和第 24 周）、干扰素 (IFN)-γ（第 8 周和第 24 周）、脂多糖结合蛋白（LBP；第 8 周和第 24 周）的绝对浓度。与无应答者相比，内镜缓解者的IL-22（第8周和第24周）和IL-22（第8周和第24周）显着降低（p值范围<0.001和<0.05）。SAA（第 8 周）和 AGP（第 24 周）是用于识别内镜缓解患者的 ROC 曲线下面积（AUROC；分别为 0.761 和 0.760）最高的生物标志物，尽管它们的性能并不优于 C 反应蛋白（ CRP）或粪便钙卫蛋白。与单一生物标志物测量相比，生物标志物组合的预测概率的 AUROC 在区分内镜缓解者和无反应者方面表现出优越性，但与粪便钙卫蛋白相比则不然。结论 虽然并不优于粪便钙卫蛋白，但在优特克单抗治疗期间测量 AGP、SAA、LBF、IFN-γ、IL-6 和 IL-22 浓度及其组合（有或没有 CRP 和粪便钙卫蛋白）可能有助于充分监测治疗CD 患者的反应。