Baseline Clearance of Infliximab Is Associated With Requirement for Colectomy in Patients With Acute Severe Ulcerative Colitis.
Baseline Clearance of Infliximab Is Associated With Requirement for Colectomy in Patients With Acute Severe Ulcerative Colitis.
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英夫利昔单抗的基线清除率与急性严重溃疡性结肠炎患者结肠切除术的需要相关
DOI：
10.1016/j.cgh.2020.03.072
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Sandborn WJ
中科院分区：
文献类型：
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作者：
Battat R;Hemperly A;Truong S;Whitmire N;Boland BS;Dulai PS;Holmer AK;Nguyen NH;Singh S;Vande Casteele N;Sandborn WJ
急性严重溃疡性结肠炎（ASUC）住院患者通常需要手术治疗。尽管肿瘤坏死因子拮抗剂英夫利昔单抗是ASUC患者预防结肠切除术的有效挽救疗法，但最佳剂量尚不清楚。计算英夫利昔单抗清除率与溃疡性结肠炎患者的重要预后相关，但其在ASUC患者中的效用尚未确定。我们评估了因ASUC住院患者在英夫利昔单抗挽救治疗前计算的基线英夫利昔单抗清除率与结肠切除术需求之间的关系。我们获得了接受英夫利昔单抗治疗的住院ASUC患者的数据。然后，我们根据现有公式计算了这些患者的基线英夫利昔单抗药物清除率。主要目的是比较6个月后需要结肠切除术的患者和不需要结肠切除术的患者之间的清除率。接受者工作特征曲线分析评估结肠切除术的清除率阈值。多变量logistic回归分析评估结肠切除术相关因素。在39例ASUC患者中，6个月时需要结肠切除术的患者的中位基线计算清除率高于不需要结肠切除术的患者（0.733 vs 0.569 L/天；P= 0.005）。英夫利昔单抗清除率阈值为0.627 L/天，识别需要结肠切除术的患者，敏感性为80.0%，特异性为82.8%（曲线下面积为0.80）。英夫利昔单抗清除率为0.627L/天及以上的患者在6个月内进行结肠切除术的比例（61.5%）高于英夫利昔单抗清除率较低的患者（7.7%）（P=.001）。多变量分析确定基线英夫利昔单抗清除率是与结肠切除术相关的唯一因素。需要结肠切除术的患者在医院的英夫利昔单抗剂量较高。30天和1天的结果相似。在住院的ASUC患者中，在给予英夫利昔单抗前计算的英夫利昔单抗清除率越高，结肠切除术率越高。虽然需要结肠切除术的患者接受了更高的剂量，但缺乏英夫利昔单抗浓度的数据。ASUC患者需要英夫利昔单抗药代动力学模型，以便进行基于清除率和标准剂量的比较试验。
Hospitalized patients with acute severe ulcerative colitis (ASUC) often require surgery. Although the tumor necrosis factor antagonist infliximab is an effective salvage therapy to prevent colectomy in patients with ASUC, optimal dosing is unclear. Calculated infliximab clearance has been associated important outcomes in patients with ulcerative colitis, but its utility in patients with ASUC has not been established. We assessed the relationship between calculated baseline infliximab clearance prior to infliximab salvage therapy and requirement for colectomy in patients hospitalized for ASUC. We obtained data from hospitalized patients with ASUC who initiated infliximab therapy. We then calculated baseline infliximab drug clearance in these patients based on an existing formula. The primary aim was to compare clearance between patients who required colectomy 6 months later and patients who did not require colectomy. Receiver operating characteristic curve analyses evaluated clearance thresholds for colectomy. Multivariable logistic regression analysis evaluated factors associated with colectomy. In 39 patients with ASUC, median baseline calculated clearance was higher in patients requiring colectomy at 6 months than in patients without colectomy (0.733 vs 0.569 L/day; P=.005). An infliximab clearance threshold of 0.627 L/day identified patients who required colectomy with 80.0% sensitivity and 82.8% specificity (area under the curve, 0.80). A higher proportion of patients with infliximab clearance of 0.627L/day or more underwent colectomy within 6 months (61.5%) than patients with lower infliximab clearance values (7.7%) (P=.001). Multivariable analysis identified baseline infliximab clearance as the only factor associated with colectomy. Infliximab dose in hospital was higher in patients who required colectomy. Results were similar at 30 days and 1 y. In patients hospitalized with ASUC, higher values of calculated infliximab clearance before infliximab administration is associated with higher rates of colectomy. Although patients who required colectomies received higher doses, data on infliximab concentrations are lacking. Infliximab pharmacokinetic models are needed for patients with ASUC, to allow comparative trials on clearance-based vs standard dosing.