Randomized, double-blind, placebo-controlled, dose-response, and preclinical safety study of transforaminal epidural etanercept for the treatment of sciatica.

2010/01/08 医学情報、先行研究紹介 前の記事へ 次の記事へ

Title:
Randomized, double-blind, placebo-controlled, dose-response, and preclinical safety study of transforaminal epidural etanercept for the treatment of sciatica.

Authors:
Cohen SP, Bogduk N, Dragovich A, Buckenmaier CC 3rd, Griffith S, Kurihara C, Raymond J, Richter PJ, Williams N, Yaksh TL.

Department of Anesthesiology, Johns Hopkins School of Medicine, Baltimore, MD 21029, USA. scohen40@jhmi.edu

Journal: Anesthesiology. 2009 May;110(5):967-9.

Abstract
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.

実験的には、神経根性疼痛疼痛がIL-1, TNF-αなどの炎症性サイトカインによって引き起こされることが分かっています。ならばヒトの臨床において、抗TNF-αを根部に投与すれば鎮痛効果が得られるはずです。しかし、これまで、実際にその効果は臨床医学的には調べられてはいません。
この著者らは、根性神経症と診断されている患者さんに硬膜外ブロック法を用いて、抗TNFを注射して、鎮痛効果を詳細に調べています。抗TNF　を 2mg 硬膜外に注射したグループでは、100％効果があり、数か月してもその効果が持続されていることを報告してます。神経因性疼痛ではない場合、炎症反応を止めることに努めることがとても大切であるということをヒトを用いて証明している貴重な論文だと思います。

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