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他尼珠单抗:一种用于慢性下背痛的选择性人源化单克隆抗体。

Tanezumab: a selective humanized mAb for chronic lower back pain.

作者信息

Webb Michael P, Helander Erik M, Menard Bethany L, Urman Richard D, Kaye Alan D

机构信息

Department of Anesthesiology, North Shore Hospital, Auckland, New Zealand.

Department of Anesthesiology, LSU School of Medicine, New Orleans, LA, USA.

出版信息

Ther Clin Risk Manag. 2018 Feb 21;14:361-367. doi: 10.2147/TCRM.S144125. eCollection 2018.

Abstract

Chronic lower back pain is a significant disease that affects nearly 20% of the worldwide population. Along with hindering patients' quality of life, chronic lower back pain is considered to be the second most common cause of disability among Americans. Treating chronic lower back pain is often a challenge for providers, especially in light of our current opioid epidemic. With this epidemic and an increased aging population, there is an imminent need for development of new pharmacologic therapeutic options, which are not only effective but also pose minimal adverse effects to the patient. With these considerations, a novel therapeutic agent called tanezumab has been developed and studied. Tanezumab is a humanized monoclonal immunoglobulin G2 antibody that works by inhibiting the binding of NGF to its receptors. NGF is involved in the function of sensory neurons and fibers involved in nociceptive transduction. It is commonly seen in excess in inflammatory joint conditions and in chronic pain patients. Nociceptors are dependent on NGF for growth and ongoing function. The inhibition of NGF binding to its receptors is a mechanism by which pain pathways can be interrupted. In this article, a number of recent randomized controlled trials are examined relating to the efficacy and safety of tanezumab in the treatment of chronic lower back pain. Although tanezumab was shown to be an effective pain modulator in major trials, several adverse effects were seen among different doses of the medication, one of which led to a clinical hold placed by the US Food and Drug Administration. In summary, tanezumab is a promising agent that warrants further investigation into its analgesic properties and safety profile.

摘要

慢性下腰痛是一种严重疾病,影响着全球近20%的人口。除了妨碍患者的生活质量外,慢性下腰痛还被认为是美国人致残的第二大常见原因。对医疗服务提供者来说,治疗慢性下腰痛往往是一项挑战,尤其是在当前阿片类药物泛滥的情况下。鉴于这种泛滥情况以及老龄化人口的增加,迫切需要开发新的药物治疗选择,这些选择不仅有效,而且对患者产生的副作用最小。基于这些考虑,一种名为他奈祖单抗的新型治疗药物已被研发并进行了研究。他奈祖单抗是一种人源化单克隆免疫球蛋白G2抗体,其作用机制是抑制神经生长因子(NGF)与其受体的结合。NGF参与感觉神经元和参与伤害性传导的纤维的功能。在炎症性关节疾病和慢性疼痛患者中,通常会过量出现NGF。伤害感受器的生长和持续功能依赖于NGF。抑制NGF与其受体的结合是一种可以中断疼痛通路的机制。在本文中,我们研究了一些近期关于他奈祖单抗治疗慢性下腰痛的疗效和安全性的随机对照试验。尽管在主要试验中他奈祖单抗被证明是一种有效的疼痛调节剂,但在不同剂量的药物中观察到了一些不良反应,其中一种导致美国食品药品监督管理局暂停了临床试验。总之,他奈祖单抗是一种有前景的药物,值得进一步研究其镇痛特性和安全性。

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