Early Infliximab Levels and Clearance Predict Outcomes After Infliximab Rescue in Acute Severe Ulcerative Colitis: Results From PREDICT-UC.

We aimed to identify whether infliximab therapeutic drug monitoring is associated with ASUC outcomes.

我们的目标是确定英夫利昔单抗治疗药物监测是否与ASUC的治疗结果相关。

Methods

Serum and stool samples were collected from patients enrolled in the PREDICT-UC randomized controlled trial(NCT02770040), which compared intensified and standard infliximab rescue in steroid-refractory ASUC.

血清和粪便样本是从参与PREDICT-UC随机对照试验（NCT02770040）的患者中收集的，该试验比较了在糖皮质激素耐药的急性重症溃疡性结肠炎中加强和标准的英夫利昔单抗救援治疗。

Infliximab levels measured after trial conclusion and clearance derived using pharmacokinetic modelling were correlated with outcomes.

试验结束后测量的英夫利昔单抗水平和使用药物动力学建模得出的清除率与结果相关联。

Results

Infliximab levels were measured in 681 serum and 198 fecal samples from 135 patients.

在135名患者的681个血清样本和198个粪便样本中测量了英夫利昔单抗的水平。

Lower day 3 serum infliximab levels predicted infliximab failure on day 14 (area under the receiver operator characteristic curve = 0.63; P = .043) and colectomy by 3 months (area under the receiver operator characteristic curve = 0.77; P = .0027); a threshold of ≤57.9 μg/mL had 83% sensitivity, 67% specificity, 24% positive predictive value, and 97% negative predictive value for colectomy.

较低的第3天血清英夫利昔单抗水平预测了第14天的英夫利昔单抗失败（接收者操作特征曲线下面积=0.63；P=0.043）和3个月内进行结肠切除术（接收者操作特征曲线下面积=0.77；P=0.0027）；≤57.9 μg/mL的阈值对结肠切除术的敏感性为83%，特异性为67%，阳性预测值为24%，阴性预测值为97%。

Patients with high clearance between day 1 and 7 (≥0.62 L/d) were more likely to respond to an initial 10 mg/kg vs 5 mg/kg infliximab dose (risk ratio, 1.50; 95% confidence interval[CI], 1.01-2.23), and had a higher risk of colectomy if they received an initial 5 mg/kg vs 10 mg/kg dose (HR, 4.81; 95% CI, 1.09-21.37).

在第1天至第7天间清除率高的患者（≥0.62 L/d）更有可能对初始10 mg/kg与5 mg/kg英夫利昔单抗剂量产生反应（风险比，1.50；95%置信区间[CI]，1.01-2.23），并且如果他们接受了初始5 mg/kg与10 mg/kg剂量，其结肠切除的风险更高（风险比，4.81；95% CI，1.09-21.37）。

In patients with high clearance who did not respond to the first infliximab dose, day 14 response rate was higher with a second 10 mg/kg vs 5 mg/kg dose (38% vs 11%; risk ratio, 3.43; 95% CI, 1.05-11.19).

在那些清除率高且对第一次英夫利昔单抗剂量没有反应的患者中，第14天的反应率在第二次使用10 mg/kg剂量时高于5 mg/kg剂量（38%对比11%；风险比，3.43；95% CI，1.05-11.19）。

Day 3 fecal infliximab levels correlated with endoscopic severity and was associated with day 7 nonresponse (P = .016).

第3天粪便中英夫利昔单抗水平与内镜下病变严重程度相关，并与第7天无反应性相关（P = .016）。

Conclusions

Early infliximab levels and clearance calculation can predict outcomes in ASUC.

早期英夫利昔单抗水平及清除率的计算可以预测急性重症溃疡性结肠炎的治疗结果。

This is the first study to demonstrate that high infliximab clearance may be overcome by intensified infliximab dosing.

这是首个研究显示，通过加强英夫利昔单抗剂量，可以克服高英夫利昔单抗清除率的问题。

(NCT02770040; Optimizing Infliximab Induction Therapy for Acute Severe Ulcerative Colitis).

(NCT02770040; 优化急性重症溃疡性结肠炎的英夫利昔单抗诱导治疗)