Pharmacokinetics of Infliximab in Children with Moderate-to-Severe Ulcerative Colitis: Results from a Randomized, Multicenter, Open-label, Phase 3 Study
Pharmacokinetics of Infliximab in Children with Moderate-to-Severe Ulcerative Colitis: Results from a Randomized, Multicenter, Open-label, Phase 3 Study
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DOI：
10.1097/01.mib.0000435438.84365.f7
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发表时间：
2013-12-01
影响因子：
4.9
通讯作者：
Hyams, Jeffrey
中科院分区：
文献类型：
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作者：
Adedokun, Omoniyi J.;Xu, Zhenhua;Hyams, Jeffrey
背景：评估英夫利西单抗在儿童溃疡性结肠炎（UC）中的药代动力学。方法：这项3期、随机、开放标签、多中心研究纳入了60名中重度活动性UC（马约评分，6-12;内镜分项评分，2）儿童（6-17岁），尽管常规治疗无效。患者在第0、2和6周接受英夫利西单抗5 mg/kg诱导输注。第8周临床应答者（n = 45）随机接受英夫利西单抗5 mg/kg给药，每8周一次（q8 w）至第46周或每12周一次（q12 w）至第42周。在英夫利西单抗维持治疗期间失去应答的患者有资格增加剂量（510 mg/kg）和/或缩短给药间隔（q12 wq 8 w）。收集血液样本进行英夫利西单抗浓度和药代动力学determinations.Results：英夫利西单抗的药代动力学不受年龄（6-11岁与12-17岁），基线免疫调节剂的使用，或UC的程度。在第8周，与血清浓度较低的患者相比，血清英夫利西单抗浓度较高（41.1 g/mL）的患者达到疗效终点（临床应答，92.9%;粘膜愈合，92.9%;临床缓解，64.3%）的比例较高。
Background:To assess infliximab pharmacokinetics in pediatric ulcerative colitis (UC).Methods:This phase 3, randomized, open-label multicenter study enrolled 60 children (6-17 yr) with moderate-to-severely active UC (Mayo score, 6-12; endoscopic subscore, 2), despite conventional therapy. Patients received infliximab 5-mg/kg induction infusions at weeks 0, 2, and 6. Week 8 clinical responders (n = 45) were randomized to infliximab 5 mg/kg given every 8 weeks (q8w) through week 46 or every 12 weeks (q12w) through week 42. Patients losing response during maintenance infliximab were eligible to increase the dose (510 mg/kg) and/or shorten the dosing interval (q12wq8w). Blood samples were collected for infliximab concentration and pharmacokinetic determinations.Results:Infliximab pharmacokinetics were not influenced by age (6-11 yr versus 12-17 yr), baseline immunomodulator use, or the extent of UC. At week 8, higher serum infliximab concentrations (41.1 g/mL) were associated with greater proportions of patients achieving efficacy endpoints (clinical response, 92.9%; mucosal healing, 92.9%; and clinical remission, 64.3%) versus those with lower serum concentrations (