Division of Pediatric Gastroenterology.
Susan B. Meister Child Health Evaluation and Research Center.
J Pediatr Gastroenterol Nutr. 2019 Jul;69(1):88-94. doi: 10.1097/MPG.0000000000002296.
Thiopurines, commonly used to treat inflammatory bowel disease, cause lymphopenia and red blood cell macrocytosis, requiring therapeutic monitoring. Mean corpuscular volume/white blood cell (MCV/WBC) ratio has been proposed as a surrogate for therapeutic monitoring. Our aim was to investigate MCV/WBC ratio for assessing clinical response to thiopurines among pediatric patients with inflammatory bowel disease.
We performed a retrospective cross-sectional study at a tertiary care center using laboratory results and standardized physician global assessments (PGA) among pediatric patients taking thiopurines. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fecal calprotectin, and 6-thioguanine nucleotides were assessed when available. The primary outcome was association between MCV/WBC ratio and clinical remission assessed by ESR, CRP, calprotectin, or PGA. We also used a composite outcome requiring all available data to be normal. Analyses were limited to 1 occurrence per patient, >60 days after starting thiopurine, and comparators were required to be within 14 days of one another.
A total of 471 patients met inclusion criteria. MCV/WBC ratio poorly predicted quiescent disease as defined by PGA (area under receiver operating characteristic curve [AuROC] 0.55, 95% confidence interval [CI] 0.43-0.66). MCV/WBC ratio better predicted quiescent disease defined as normal CRP (AuROC 0.64, 95% CI 0.58-0.70) or normal ESR (AuROC 0.59, 95% CI 0.52-0.66). When the composite outcome measure was used, MCV/WBC ratio had an AuROC of 0.65 (95% CI 0.59-0.70), indicating it is reasonably accurate in discriminating between clinical remission and active disease.
MCV/WBC ratio is a noninferior, easy, and low-cost alternative to thiopurine metabolite monitoring.
硫嘌呤类药物常用于治疗炎症性肠病,会导致淋巴细胞减少和红细胞体积增大,需要进行治疗监测。平均红细胞体积/白细胞(MCV/WBC)比值已被提出作为治疗监测的替代指标。我们的目的是研究 MCV/WBC 比值在评估炎症性肠病儿科患者接受硫嘌呤类药物治疗的临床反应中的作用。
我们在一家三级医疗中心进行了一项回顾性横断面研究,使用实验室结果和标准化医生总体评估(PGA)来评估接受硫嘌呤类药物治疗的儿科患者。在有条件的情况下,评估红细胞沉降率(ESR)、C 反应蛋白(CRP)、粪便钙卫蛋白和 6-硫鸟嘌呤核苷酸。主要结局是 MCV/WBC 比值与 ESR、CRP、钙卫蛋白或 PGA 评估的临床缓解之间的关联。我们还使用了需要所有可用数据均正常的复合结局。分析仅限于每位患者 1 次发作,且在开始使用硫嘌呤类药物后 >60 天,并且比较组之间需要间隔 14 天。
共有 471 名患者符合纳入标准。MCV/WBC 比值预测 PGA 定义的疾病静止状态的效果不佳(接受者操作特征曲线 [AuROC] 0.55,95%置信区间 [CI] 0.43-0.66)。MCV/WBC 比值预测 CRP 正常(AuROC 0.64,95%CI 0.58-0.70)或 ESR 正常(AuROC 0.59,95%CI 0.52-0.66)定义的疾病静止状态的效果更好。当使用复合结局测量时,MCV/WBC 比值的 AuROC 为 0.65(95%CI 0.59-0.70),表明其在区分临床缓解与活动期疾病方面具有相当的准确性。
MCV/WBC 比值是一种非劣效、简便且低成本的硫嘌呤类药物代谢物监测替代方法。