Randomized, Double-blind, Placebo-controlled, Dose-response, and Preclinical Safety Study of Transforaminal Epidural Etanercept for the Treatment of Sciatica
Randomized, Double-blind, Placebo-controlled, Dose-response, and Preclinical Safety Study of Transforaminal Epidural Etanercept for the Treatment of Sciatica
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DOI：
10.1097/aln.0b013e3181a05aa0
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发表时间：
2009-05-01
期刊：
影响因子：
8.8
通讯作者：
Yaksh, Tony L.
中科院分区：
文献类型：
--
作者：
Cohen, Steven P.;Bogduk, Nikolai;Yaksh, Tony L.
背景：最近的证据表明炎性细胞因子肿瘤坏死因子是神经根病的主要原因。然而，尽管全身给予肿瘤坏死因子抑制剂的开放标签研究已经产生了积极的结果，但安慰剂对照研究未能证明疗效。可能导致不良结果的一个变量是神经炎症部位的低药物水平。到目前为止，没有研究评估的疗效或安全性，urally管理的抗肿瘤坏死因子agents.Methods：一个双盲，安慰剂对照，剂量反应研究进行了评估硬膜外肿瘤坏死因子抑制剂。24例亚急性腰骶神经根病患者被随机分配至连续8组，分别接受2、4或6 mg恩那西普经椎间孔硬膜外注射，间隔2周。在每组中，两名患者接受硬膜外盐水。一个平行的硬膜外犬的安全性研究进行了使用相同的注射剂量和范例，在临床study.Results：动物和人类的安全性研究显示，没有行为，神经，或组织学证据的药物相关的毒性。在临床组中，治疗后一个月，依那西普治疗组患者的腿部和背部疼痛总体上得到了显著改善，但生理盐水组没有。生理盐水组1例患者（17%）、2 mg组6例患者（100%）以及4 mg和6 mg组各4例患者（67%）报告治疗后1个月腿部疼痛至少减轻50%，总体感知效果为阳性。治疗6个月后，除了一名patient.Conclusion：硬膜外恩那西普作为腰骶神经根病的治疗方法有希望。
Background: Recent evidence implicates the inflammatory cytokine tumor necrosis factor as a major cause of radiculopathy. Yet, whereas open-label studies with systemically delivered tumor necrosis factor inhibitors have yielded positive results, a placebo-controlled study failed to demonstrate efficacy. One variable that may have contributed to poor outcomes is low drug levels at the site of nerve inflammation. To date, no studies have evaluated the efficacy or safety of epidurally administered anti-tumor necrosis factor agents.Methods: A double-blind, placebo-controlled, dose-response study was conducted to evaluate an epidural tumor necrosis factor inhibitor. Twenty-four patients with subacute lumbosacral radiculopathy were randomly assigned to receive two transforaminal epidural injections of 2, 4, or 6 mg of entanercept 2 weeks apart in successive groups of eight. In each group, two patients received epidural saline. A parallel epidural canine safety study was conducted using the same injection doses and paradigm as in the clinical study.Results: The animal and human safety studies revealed no behavioral, neurologic, or histologic evidence of drug-related toxicity. In the clinical arm, significant improvements in leg and back pain were collectively noted for the etanercept-treated patients, but not for the saline group, one month after treatment. One patient in the saline group (17%), six patients In the 2-mg group (100%), and four patients each in the 4-mg and 6-mg groups (67%) reported at least 50% reduction in leg pain and a positive global perceived effect one month after treatment. Six months after treatment, the beneficial effects persisted in all but one patient.Conclusion: Epidural entanercept holds promise as a treatment for lumbosacral radiculopathy.