Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Inflammatory Bowel Disease Group, Division of Gastroenterology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada.
Inflamm Bowel Dis. 2021 Aug 19;27(9):1452-1461. doi: 10.1093/ibd/izaa309.
Up to 60% of patients with ulcerative colitis (UC) ultimately fail anti-tumor necrosis factor (TNF) treatment. We aimed to investigate early predictive markers of clinical and endoscopic outcomes in patients with UC who were anti-TNF-naïve commencing anti-TNF treatment, with particular focus on changes in albumin and C-reactive protein levels in the first 2 weeks of treatment.
We retrospectively investigated 210 patients with UC who started infliximab or adalimumab between 2009 and 2016 (male, 62.4%; median age at diagnosis, 37.9 years [interquartile range, 25.5-48.9 years]; median follow-up duration, 3.3 years [1.9-5.0 years]). Logistic and Cox proportional-hazards regressions were performed to identify variables associated with primary nonresponse (PNR), endoscopic outcomes, time-to-colectomy, and anti-TNF failure.
Forty-one patients (19.5%) experienced PNR; week 0/week 2 ratio serum albumin was associated with PNR (adjusted odds ratio [aOR], 1.8; 95% confidence interval [CI], 1.1-2.9, per interquartile range increase). Week 0/week 2 ratio albumin was also associated with endoscopic response (aOR, 0.28; 95% CI, 0.31-0.82) and endoscopic remission (aOR, 0.61; 95% CI, 0.39-0.96) at weeks 8 to 14, time-to-colectomy (adjusted hazard ratio, 2.12; 95% CI, 1.29-3.49) and time-to-anti-TNF failure (adjusted hazard ratio, 1.54; 95% CI, 1.22-1.96), regardless of age, disease severity, or in-patient status. Association with time-to-colectomy and anti-TNF failure was externally validated in an independent cohort of inpatients with UC starting infliximab.
Change in serum albumin within the first 2 weeks of anti-TNF treatment is predictive of PNR, endoscopic outcomes, time-to-colectomy, and anti-TNF failure in patients with UC. Timely access to this biomarker enables early identification of patients with UC at risk of anti-TNF failure and may guide early optimization of anti-TNF treatment to improve disease outcomes.
多达 60%的溃疡性结肠炎 (UC) 患者最终会对抗肿瘤坏死因子 (TNF) 治疗产生耐药。本研究旨在探讨初治 UC 患者在接受抗 TNF 治疗后，其临床和内镜结局的早期预测标志物，特别关注治疗最初 2 周内白蛋白和 C 反应蛋白水平的变化。
我们回顾性分析了 2009 年至 2016 年间开始使用英夫利昔单抗或阿达木单抗治疗的 210 例 UC 患者（男性 62.4%；诊断时中位年龄 37.9 岁 [四分位距 25.5-48.9 岁]；中位随访时间 3.3 年 [1.9-5.0 年]）。采用 logistic 和 Cox 比例风险回归分析鉴定与原发性无应答（PNR）、内镜结局、结肠切除术时间和抗 TNF 失败相关的变量。
41 例患者（19.5%）发生 PNR；治疗最初 2 周内血清白蛋白的周 0/周 2 比值与 PNR 相关（校正优势比 [aOR]，1.8；95%置信区间 [CI]，1.1-2.9，每四分位距增加）。周 0/周 2 比值白蛋白也与第 8 至 14 周时的内镜应答（aOR，0.28；95%CI，0.31-0.82）和内镜缓解（aOR，0.61；95%CI，0.39-0.96）、结肠切除术时间（校正风险比，2.12；95%CI，1.29-3.49）和抗 TNF 失败时间（校正风险比，1.54；95%CI，1.22-1.96）相关，与年龄、疾病严重程度或住院状态无关。在接受英夫利昔单抗治疗的 UC 住院患者的独立队列中，对与结肠切除术时间和抗 TNF 失败时间的相关性进行了外部验证。
在接受抗 TNF 治疗最初 2 周内血清白蛋白的变化可预测 UC 患者的 PNR、内镜结局、结肠切除术时间和抗 TNF 失败。及时获得该生物标志物可使 UC 患者中存在抗 TNF 治疗失败风险的患者尽早得到识别，并可能指导早期优化抗 TNF 治疗以改善疾病结局。
