Seow Cynthia H, Marshall John K, Stewart Erin, Pettengell Christopher, Ward Ryan, Afif Waqqas
Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
Division of Gastroenterology, Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton Ontario, Canada.
J Can Assoc Gastroenterol. 2024 Mar 24;7(4):290-298. doi: 10.1093/jcag/gwae010. eCollection 2024 Aug.
Therapeutic drug monitoring is used to optimize anti-tumour necrosis factor biologic effectiveness in inflammatory bowel disease, but its role with other biological classes is unclear. This study explores relationships between post-induction vedolizumab trough concentrations and biochemical outcomes in a real-world study of individuals with inflammatory bowel disease.
This retrospective analysis of data from a national patient support program between 2018 and 2020, included 436 individuals with Crohn's disease or ulcerative colitis receiving vedolizumab. Optimal vedolizumab concentration thresholds (at weeks 6 and 14) were determined based on their ability to predict biochemical normalization (week 30 faecal calprotectin [<250 µg/g], C-reactive protein [<5 mg/l]). Thresholds best associated with each outcome were evaluated in multivariate analyses.
Among patients with Crohn's disease, week 6 serum vedolizumab concentrations (>41.65 µg/ml) predicted normalization defined by C-reactive protein: Spearman correlation coefficient [] = -0.26, = 0.002 and multivariate analysis (MVA)-OR: 3.22, 95% CI: 1.32-7.87, = 0.01, and at week 14 (>22.25 µg/ml): = -0.38, < 0.0001, and MVA-OR: 3.21, 95% CI: 1.26-8.17 but not faecal calprotectin. Similarly, among patients with ulcerative colitis, week 6 vedolizumab concentrations (>39.65 g/ml) predicted normalization defined by C-reactive protein: = -0.26, = 0.005 and MVA-OR: 4.03, 95% CI: 1.30-12.52, = 0.016, and at week 14 (>17.35 µg/ml): = -0.39, = 0.0001 and MVA-OR: 6.95, 95% CI: 1.81-26.77, = 0.005, but not faecal calprotectin.
Induction and post-induction serum vedolizumab were not consistently associated with biochemical normalization. As such, proactive therapeutic drug monitoring for vedolizumab should not be routinely incorporated in a treat to target strategy for inflammatory bowel disease.
NCT04567628.
治疗药物监测用于优化抗肿瘤坏死因子生物制剂在炎症性肠病中的疗效，但其在其他生物制剂类别中的作用尚不清楚。本研究在一项针对炎症性肠病患者的真实世界研究中，探讨诱导治疗后维多珠单抗谷浓度与生化指标结果之间的关系。
对2018年至2020年期间一个全国性患者支持项目的数据进行回顾性分析，纳入436例接受维多珠单抗治疗的克罗恩病或溃疡性结肠炎患者。根据维多珠单抗预测生化指标正常化（第30周粪便钙卫蛋白[<250μg/g]、C反应蛋白[<5mg/l]）的能力，确定最佳浓度阈值（第6周和第14周）。在多变量分析中评估与各结果最相关的阈值。
在克罗恩病患者中，第6周血清维多珠单抗浓度（>41.65μg/ml）可预测C反应蛋白定义的正常化：Spearman相关系数[]=-0.26，=0.002，多变量分析（MVA）-OR：3.22，95%CI：1.32-7.87，=0.01；第14周（>22.25μg/ml）：=-0.38，<0.0001，MVA-OR：3.21，95%CI：1.26-8.17，但与粪便钙卫蛋白无关。同样，在溃疡性结肠炎患者中，第6周维多珠单抗浓度（>39.65μg/ml）可预测C反应蛋白定义 的正常化：=-0.26，=0.005，MVA-OR：4.03，95%CI：1.30-12.52，=0.016；第14周（>17.35μg/ml）：=-0.39，=0.0001，MVA-OR：6.95，95%CI：1.81-26.77，=0.005，但与粪便钙卫蛋白无关。
诱导治疗期及诱导治疗后的血清维多珠单抗浓度与生化指标正常化并非始终相关。因此，在炎症性肠病的靶向治疗策略中，不应常规进行维多珠单抗的主动治疗药物监测。
NCT04567628
