Trough Concentrations of Infliximab Guide Dosing for Patients With Inflammatory Bowel Disease
Trough Concentrations of Infliximab Guide Dosing for Patients With Inflammatory Bowel Disease
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DOI：
10.1053/j.gastro.2015.02.031
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发表时间：
2015-06-01
期刊：
影响因子：
29.4
通讯作者：
Vermeire, Severine
中科院分区：
文献类型：
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作者：
Vande Casteele, Niels;Ferrante, Marc;Vermeire, Severine
背景与目的：英夫利昔单抗是一种肿瘤坏死因子拮抗剂，可有效治疗克罗恩病（CD）和溃疡性结肠炎（UC）。我们的目的是确定基于治疗药物监测的给药是否会增加缓解率，以及在维持CD和UC患者的缓解方面，基于浓度的持续给药是否优于基于临床的英夫利昔单抗给药。方法：我们在一家三级转诊中心进行了一项为期1年的随机对照试验，包括263名对维持英夫利昔单抗治疗有稳定反应的成年人（178名CD患者和85名UC患者）。使用算法增加或减少剂量，使所有患者达到3-7 μ g/mL的目标谷浓度（TC）（优化阶段）。根据患者的临床特征（n = 123）将患者随机（1:1）分配到接受英夫利昔单抗治疗的组（n = 128）或根据tc继续给药的组（维持期）。主要终点为优化期后1年的临床和生化缓解。结果：筛查时，263例患者中有115例英夫利昔单抗TC为3-7 μ g/mL（43.7%）。76例TCs为7 μ g/mL的患者中，67例（93%）患者减量后TCs达到3-7 μ g/mL。这导致药物成本比减量前降低28% （P < 0.001）。66%基于临床特征给药的患者和69%基于TC给药的患者达到缓解，主要终点（P = 0.686）。接受临床基础给药的患者有21例（17%）复发，接受浓度基础给药的患者有9例（7%）复发（P = 0.018）。结论：将患者的英夫利昔单抗tc靶向至3-7 μ g/mL可更有效地使用该药物。在剂量优化后，持续以浓度为基础的剂量在1年后达到缓解并不优于以临床为基础的剂量，但在治疗过程中与较少的耀斑相关。ClinicalTrialsRegister。欧盟编号：2011-002061-38。
BACKGROUND & AIMS: Infliximab, a tumor necrosis factor antagonist, is effective for treating patients with Crohn's disease (CD) and ulcerative colitis (UC). We aimed to determine whether dosing based on therapeutic drug monitoring increases rate of remission and whether continued concentration-based dosing is superior to clinically based dosing of infliximab for maintaining remission in patients with CD and UC. METHODS: We performed a 1-year randomized controlled trial at a tertiary referral center, including 263 adults (178 with CD and 85 with UC) with stable responses to maintenance infliximab therapy. Doses were escalated or reduced using an algorithm to reach a target trough concentration (TC) of 3-7 mu g/mL in all patients (optimization phase). Patients were randomly assigned (1:1) to groups that received infliximab dosing based on their clinical features (n = 123) or continued dosing based on TCs (n = 128) (maintenance phase). The primary end point was clinical and biochemical remission at 1 year after the optimization phase. RESULTS: At screening, 115 of 263 patients had a TC of infliximab of 3-7 mu g/mL (43.7%). Of 76 patients with TCs 7 mu g/mL, 67 patients (93%) achieved TCs of 3-7 mu g/mL after dose reduction. This resulted in a 28% reduction in drug cost from before dose reduction (P < .001). Sixty-six percent of patients whose dosing was based on clinical features and 69% whose dosing was based on TC achieved remission, the primary end point (P = .686). Disease relapsed in 21 patients who received clinically based dosing (17%) and 9 patients who received concentration-based dosing (7%) (P = .018). CONCLUSIONS: Targeting patients' infliximab TCs to 3-7 mu g/mL results in a more efficient use of the drug. After dose optimization, continued concentration-based dosing was not superior to clinically based dosing for achieving remission after 1 year, but was associated with fewer flares during the course of treatment. ClinicalTrialsRegister.eu number: 2011-002061-38.