使用粪便钙卫蛋白联合英夫利昔单抗谷浓度预测克罗恩病临床复发的模型的开发与内部验证
Development and Internal Validation of a Model Using Fecal Calprotectin in Combination with Infliximab Trough Levels to Predict Clinical Relapse in Crohn's Disease.
作者信息
Roblin Xavier, Duru Gerard, Williet Nicolas, Del Tedesco Emilie, Cuilleron Murielle, Jarlot Camille, Phelip Jean Marc, Boschetti Gilles, Flourié Bernard, Nancey Stephane, Peyrin-Biroulet Laurent, Paul Stephane
机构信息
*Department of Gastroenterology, University Hospital of Saint Etienne, France; †Mathematic Unit, University Claude Bernard, Lyon, France; ‡Department of Radiology, University Hospital of Saint Etienne, France; §Department of Gastroenterology, CHU, Lyon Sud, Lyon, France; ‖Department of Gastroenterology and Inserm, University Hospital of Nancy, Lorraine University, Vandoeuvre-les-Nancy, France; and ¶Department of Immunology, University Hospital of Saint Etienne, Saint Etienne, France.
出版信息
Inflamm Bowel Dis. 2017 Jan;23(1):126-132. doi: 10.1097/MIB.0000000000000986.
BACKGROUND
The best noninvasive method predicting clinical relapse remains undetermined in infliximab (IFX)-treated patients with Crohn's disease.
METHODS
All patients with CD on IFX maintenance treatment and in clinical remission for at least 16 weeks, between 2011 and 2014, were enrolled in a prospective single-center study. The Crohn's Disease Activity Index (CDAI), fecal calprotectin, C-reactive protein levels, antibodies (ATI), and trough level (TLI) of IFX were measured at every IFX infusion. The best thresholds of TLI (2 versus 3 μg/mL) and calprotectin (50 versus 250 μg/g stools) were identified across four logistic regression models.
RESULTS
One hundred nineteen patients (mean age: 34 ± 12 yrs, mean disease duration: 7.8 yrs) were included. Mean follow-up was 20.4 months, and 17% of the patients were on IFX and azathioprine at inclusion. During follow-up, 37 patients (31.1%) relapsed, 78% within the first 6 months. The clinical characteristics of the relapsed and nonrelapsed patients were similar. After logistic regression, fecal calprotectin >250 μg/g stools (OR: 4.09; 95% CI, 1.01-16.21; P = 0.049) and TLI <2 μg/mL (OR: 14.85; 95% CI, 3.67-60; P < 0.0001) were associated with loss of response. A training cohort of 55 patients was isolated randomly to implement prediction rules for loss of response. The best predictive rules were the combination of a TLI <2 μg/mL and a fecal calprotectin level >250 μg/g stools (78.3%). These rules were validated on a test cohort of 64 patients with an accuracy of 87%, (sensitivity = 0.94, specificity = 0.84, positive predictive value = 0.73, and negative predictive value = 0.97).
CONCLUSIONS
In IFX-treated patients with CD in clinical remission, a combination of TLI (<2 μg/mL) and fecal calprotectin (>250 μg/g of stools) is a good model for predicting loss of response. In contrast with previous data, low TLIs ranging from 2 to 3 μg/mL should neither systematically lead to the optimization of IFX use nor a switch in the treatment.
背景
在接受英夫利昔单抗（IFX）治疗的克罗恩病患者中，预测临床复发的最佳非侵入性方法尚未确定。
方法
2011年至2014年期间，所有接受IFX维持治疗且临床缓解至少16周的克罗恩病患者均纳入一项前瞻性单中心研究。每次输注IFX时均测量克罗恩病活动指数（CDAI）、粪便钙卫蛋白、C反应蛋白水平、抗体（ATI）以及IFX的谷浓度（TLI）。在四个逻辑回归模型中确定了TLI（2 μg/mL与3 μg/mL）和钙卫蛋白（50 μg/g粪便与250 μg/g粪便）的最佳阈值。
结果
纳入119例患者（平均年龄：34±12岁，平均病程：7.8年）。平均随访20.4个月，17%的患者在纳入时同时使用IFX和硫唑嘌呤。随访期间，37例患者（31.1%）复发，78%在最初6个月内复发。复发和未复发患者的临床特征相似。经过逻辑回归分析，粪便钙卫蛋白>250 μg/g粪便（比值比：4.09；95%置信区间，1.01 - 16.21；P = 0.049）和TLI<2 μg/mL（比值比：14.85；95%置信区间，3.67 - 60；P < 0.0001）与反应丧失相关。随机选取55例患者组成训练队列以实施反应丧失的预测规则。最佳预测规则是TLI<2 μg/mL与粪便钙卫蛋白水平>250 μg/g粪便的组合（78.3%）。这些规则在64例患者的测试队列中得到验证，准确率为87%（敏感性 = 0.94，特异性 = 0.84，阳性预测值 = 0.73，阴性预测值 = 0.97）。
结论
在接受IFX治疗且临床缓解的克罗恩病患者中，TLI（<2 μg/mL）和粪便钙卫蛋白（>250 μg/g粪便）的组合是预测反应丧失的良好模型。与先前数据相反，2至3 μg/mL的低TLI既不应系统性地导致IFX使用的优化，也不应导致治疗方案的改变。
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