Thomann Anne Kerstin, Schulte Lucas-Alexander, Globig Anna-Maria, Hoffmann Peter, Klag Thomas, Itzel Timo, Teufel Andreas, Schreiner Rupert, Scheffe Nina, Ebert Matthias Philip, Wehkamp Jan, Gauss Annika, Hasselblatt Peter, Klaus Jochen, Reindl Wolfgang
Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Department of Medicine I, University Hospital Ulm, Ulm, Germany.
Z Gastroenterol. 2020 May;58(5):439-444. doi: 10.1055/a-1088-1461. Epub 2020 Feb 11.
The role of therapeutic drug monitoring (TDM) in ustekinumab (UST) therapy for Crohn's disease (CD) has not been established, as only few studies have analyzed the relationship between UST serum concentrations and clinical outcome. In this pilot study, we retrospectively examined the potential of UST-concentrations (cUST) 8 weeks after induction (cUSTw8) to predict clinical response at week 16.
Serum samples and clinical data from patients (n = 72) with moderate to severely active CD who received intravenous induction with UST were retrospectively analyzed. cUST were quantitated using liquid chromatography-tandem mass spectrometry (LC-MSMS). A receiver-operating characteristic (ROC) curve and area under ROC curve (AUROC) was computed to analyze the predictive potential of cUSTw8 for clinical response at week 16 and to determine the minimal therapeutic UST trough concentration.
Forty-four patients (61 %) achieved clinical response to UST therapy at week 16. cUSTw8 was moderately effective to predict clinical response with a minimal therapeutic cUSTw8 of 2.0 mg/l (AUC 0.72, p = 0.001).
Trough concentrations of UST 8 weeks after induction predict clinical response to therapy in week 16 with moderate sensitivity and specificity. TDM using LC-MSMS could prove beneficial in personalized UST therapy of patients with CD by identifying individuals with subtherapeutic concentrations who might benefit from dose escalation.
治疗药物监测（TDM）在优特克单抗（UST）治疗克罗恩病（CD）中的作用尚未明确，因为仅有少数研究分析了UST血清浓度与临床结局之间的关系。在这项前瞻性研究中，我们回顾性研究了诱导治疗8周后UST浓度（cUSTw8）预测第16周临床反应的可能性。
回顾性分析72例中度至重度活动性CD患者静脉注射UST诱导治疗后的血清样本和临床数据。采用液相色谱-串联质谱法（LC-MSMS）定量检测cUST。计算受试者工作特征（ROC）曲线和ROC曲线下面积（AUROC），以分析cUSTw8预测第16周临床反应的潜力，并确定UST的最低治疗谷浓度。
44例患者（61%）在第16周时对UST治疗取得临床反应。cUSTw8对临床反应具有中等预测效力，最低治疗cUSTw8为2.0mg/l（AUC 0.72，p=0.001）。
诱导治疗8周后的UST谷浓度对第16周的治疗临床反应具有中等敏感性和特异性的预测作用。通过液相色谱-串联质谱法进行治疗药物监测，可识别UST浓度未达治疗标准、可能从剂量增加中获益的患者，从而为CD患者的个性化UST治疗提供帮助。
