Schnitzer T J, Marks J A
Northwestern University Feinberg School of Medicine, 303 E. Chicago Avenue, Chicago, IL, 60611, USA.
Osteoarthritis Cartilage. 2015 Jan;23 Suppl 1:S8-17. doi: 10.1016/j.joca.2014.10.003.
To evaluate the efficacy and safety of anti-NGF antibody treatment in hip and knee osteoarthritis (OA), a systematic review and meta-analysis was undertaken utilizing the criteria described by the Cochrane collaboration. Both published and unpublished trials were identified for tanezumab, fulranumab and fasinumab in hip and knee OA; sponsors were contacted to provide and confirm data. Study quality was assessed by Jadad criteria; efficacy and safety data were extracted independently by two individuals and meta-analyses were performed using Revman 5.2. 13 randomized, controlled trials were identified: 10 of tanezumab, two of fulranumab and one with fasinumab. All agents demonstrated superiority in efficacy compared to placebo. The highest doses in the phase II studies of tanezumab had a standardized effect size for WOMAC pain of 0.73 (CI, 0.51, 0.95). Subsequent phase III studies of tanezumab and phase II studies of fulranumab and fasinumab reported standardized effect sizes for WOMAC pain of -0.15-0.5, with no clear distinction among dose levels. Tanezumab compared to NSAIDs and opioids showed greater efficacy with a standardized effect size for WOMAC pain of 0.23 (CI 0.17-0.29). WOMAC function and PGA results were similar to WOMAC pain. Safety, determined by odds ratios of withdrawals from studies due to adverse events (AEs), was better at the lower doses than higher doses and similar among all agents. These results demonstrate that antibodies to NGF provide efficacy in OA and that general safety at the lower doses appears similar to placebo. Additional data on both efficacy and safety of these antibodies are needed to define the optimal dose to maximize benefit to risk.
为评估抗神经生长因子（NGF）抗体治疗髋膝关节骨关节炎（OA）的疗效和安全性，我们依据Cochrane协作网描述的标准进行了一项系统评价和荟萃分析。我们检索了已发表和未发表的关于他尼珠单抗、氟罗珠单抗和法西珠单抗治疗髋膝关节OA的试验；联系了申办方以获取并确认数据。采用Jadad标准评估研究质量；疗效和安全性数据由两名研究人员独立提取，并使用RevMan 5.2进行荟萃分析。共纳入13项随机对照试验：他尼珠单抗10项、氟罗珠单抗2项、法西珠单抗1项。与安慰剂相比，所有药物均显示出疗效优势。他尼珠单抗II期研究中的最高剂量，WOMAC疼痛的标准化效应量为0.73（95%CI：0.51，0.95）。随后他尼珠单抗的III期研究以及氟罗珠单抗和法西珠单抗的II期研究报告WOMAC疼痛的标准化效应量为-0.15至0.5，各剂量水平之间无明显差异。与非甾体抗炎药和阿片类药物相比，他尼珠单抗的疗效更佳，WOMAC疼痛的标准化效应量为0.23（95%CI：0.17，0.29）。WOMAC功能和医师整体评估（PGA）结果与WOMAC疼痛相似。安全性通过因不良事件（AE）退出研究的比值比来确定，较低剂量时安全性优于较高剂量，且所有药物之间相似。这些结果表明，抗NGF抗体在OA治疗中具有疗效，且较低剂量时总体安全性与安慰剂相似。需要更多关于这些抗体疗效和安全性的数据来确定最佳剂量，以实现效益风险最大化。
