特耐珠单抗治疗膝骨关节炎疼痛。
Tanezumab for the treatment of pain from osteoarthritis of the knee.
机构信息
Department of Medicine, University of California at Davis Medical School, Sacramento, CA 95817, USA.
出版信息
N Engl J Med. 2010 Oct 14;363(16):1521-31. doi: 10.1056/NEJMoa0901510. Epub 2010 Sep 29.
BACKGROUND
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.
METHODS
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 McMaster 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.
RESULTS
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%).
CONCLUSIONS
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, NCT00394563.).
背景
在受伤或发炎组织中神经生长因子表达增加与疼痛增加有关。这项概念验证研究旨在研究结合并抑制神经生长因子的人源化单克隆抗体 tanezumab 的安全性和镇痛疗效。
方法
我们将 450 名膝关节骨关节炎患者随机分为 tanezumab（10、25、50、100 或 200μg/公斤体重）或安慰剂组，分别于第 1 天和第 56 天给药。主要疗效指标为步行时膝关节疼痛和患者对治疗的总体反应评估。我们还使用 Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)评估疼痛、僵硬和身体功能；使用美国风湿病学会和骨关节炎研究学会国际临床试验反应标准倡议制定的反应标准（Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative，OMERACT-OARSI）评估反应率；并评估安全性。
结果
在第 1 周到第 16 周期间，与安慰剂组相比，各种剂量的 tanezumab 使步行时膝关节疼痛的平均缓解率从 45%到 62%（P<0.001）。与安慰剂组相比，tanezumab 治疗还与患者整体评估测量中治疗反应的显著改善相关（各种剂量的 tanezumab 平均增加 29%到 47%，而安慰剂组为 19%；P≤0.001）。根据 OMERACT-OARSI 标准，tanezumab 治疗组的反应率为 74%至 93%，而安慰剂组为 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%。tanezumab 治疗组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%）。
结论
在这项概念验证研究中，tanezumab 治疗与膝关节中度至重度骨关节炎患者的关节疼痛减轻和功能改善相关，同时伴有轻度和中度不良事件。（由 Rinat Neuroscience 资助；ClinicalTrials.gov 编号，NCT00394563）。
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