Tanezumab for the treatment of pain from osteoarthritis of the knee.
Tanezumab for the treatment of pain from osteoarthritis of the knee.
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DOI：
10.1056/nejmoa0901510
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发表时间：
2010-10-14
期刊：
影响因子：
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通讯作者：
Brown MT
中科院分区：
文献类型：
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作者：
Lane NE;Schnitzer TJ;Birbara CA;Mokhtarani M;Shelton DL;Smith MD;Brown MT
神经生长因子在受伤或发炎组织中的表达增加与疼痛增加有关。这项概念验证研究旨在研究tanezumab的安全性和止痛效果，tanezumab是一种人源化的单抗，可结合和抑制神经生长因子。我们随机分配了450名膝骨性关节炎患者在第1天和第56天接受tanezumab(剂量分别为每公斤体重10、25、50、100或200μg)或安慰剂。主要的疗效衡量标准是行走时的膝关节疼痛和患者对治疗反应的总体评估。我们还使用西安大略省和Mc-Master大学骨关节炎指数(WOMAC)评估了疼痛、僵硬和身体功能；使用风湿病委员会和骨关节炎研究学会国际临床试验反应标准常设委员会(OMERACT-OARSI)的结果衡量标准的应答率；以及安全性。从第1周到第16周的平均值来看，服用不同剂量的tanezumab后，行走时膝关节疼痛的平均降幅为45%至62%，而安慰剂组的降幅为22%(P<；0.001)。与安慰剂相比，与安慰剂相比，通过使用患者的总体评估指标进行评估，Tanezumab的治疗反应也有显著的改善(不同剂量的Tanezumab的平均得分增加了29%至47%，而安慰剂的得分增加了19%；P≤0.001)。根据OMERACT-OARSI标准，使用tanezumab治疗的有效率为74%至93%，而使用安慰剂的有效率为44%(P<；0.001)。Tanezumab组和安慰剂组的不良事件发生率分别为68%和55%。接受tanezumab治疗的患者中最常见的不良事件是头痛(9%的患者)、上呼吸道感染(7%)和感觉异常(7%)。在这项概念验证研究中，在患有中到重度膝骨性关节炎的患者中，使用tanezumab治疗与关节疼痛的减轻和功能的改善以及轻微和中度的不良反应有关。(由Rinat NeuroScience资助；ClinicalTrials.gov编号，。)
Increased expression of nerve growth factor in injured or inflamed tissue is associated with increased pain. This proof-of-concept study was designed to investigate the safety and analgesic efficacy of tanezumab, a humanized monoclonal antibody that binds and inhibits nerve growth factor. We randomly assigned 450 patients with osteoarthritis of the knee to receive tanezumab (administered at a dose of 10, 25, 50, 100, or 200 μg per kilogram of body weight) or placebo on days 1 and 56. The primary efficacy measures were knee pain while walking and the patient’s global assessment of response to therapy. We also assessed pain, stiffness, and physical function using the Western Ontario and Mc-Master Universities Osteoarthritis Index (WOMAC); the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI); and safety. When averaged over weeks 1 through 16, the mean reductions from baseline in knee pain while walking ranged from 45 to 62% with various doses of tanezumab, as compared with 22% with placebo (P<0.001). Tanezumab, as compared with placebo, was also associated with significantly greater improvements in the response to therapy as assessed with the use of the patients’ global assessment measure (mean increases in score of 29 to 47% with various doses of tanezumab, as compared with 19% with placebo; P≤0.001). The rate of response according to the OMERACT-OARSI criteria ranged from 74 to 93% with tanezumab treatment, as compared with 44% with placebo (P<0.001). The rates of adverse events were 68% and 55% in the tanezumab and placebo groups, respectively. The most common adverse events among tanezumab-treated patients were headache (9% of the patients), upper respiratory tract infection (7%), and paresthesia (7%). In this proof-of-concept study, treatment with tanezumab was associated with a reduction in joint pain and improvement in function, with mild and moderate adverse events, among patients with moderate-to-severe osteoarthritis of the knee. (Funded by Rinat Neuroscience; ClinicalTrials.gov number, .)