Lascelles B Duncan X, Knazovicky David, Case Beth, Freire Mila, Innes John F, Drew Alexander C, Gearing David P
Comparative Pain Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
BMC Vet Res. 2015 Apr 30;11:101. doi: 10.1186/s12917-015-0413-x.
There is a critical need for proven drugs other than non-steroidal anti-inflammatory drugs for treatment of degenerative joint disease (DJD) pain in dogs. Antibodies against nerve growth factor (NGF) are analgesic in rodent models and in humans with DJD. This pilot study aimed to evaluate the efficacy of a novel caninised anti-NGF antibody (NV-01) for the treatment of DJD pain in dogs. In a randomized, parallel group, stratified, double masked, placebo controlled, proof of principle clinical pilot study design, 26 dogs with DJD received NV-01 (200 mcg/kg IV) or placebo on day 0 (D0). In addition to objective accelerometry measures, owners completed clinical metrology instruments (Client-Specific Outcome Measures [CSOM], Canine Brief Pain Inventory [CBPI] and Liverpool Osteoarthritis in Dogs Index [LOAD]) on D0, D14 and D28. CBPI subscales (pain severity [PS] and pain interference [PI]), CSOM and LOAD scores were evaluated within and between groups for change over time. Recognized success/failure criteria were applied and success compared between groups.
CBPI PS and PI scores significantly improved in the NV-01 group (PS: D0-14, P = 0.012 and D0-28, P = 0.019; PI: D0-14, P = 0.012 and D0-28, P = 0.032) but not in the placebo group. CSOM scores showed similar patterns with a significant difference between within-group changes at D14 and D28 (P = 0.038 and P = 0.009, respectively), and significantly more successes at D28 (P = 0.047). LOAD scores significantly improved in the NV-01 group (D0-14, P = 0.004 and D0-28, P = 0.002) but not in the placebo group. There were significant differences between the groups for change in LOAD score at D14 (P = 0.014) and D28 (P = 0.033). No side effects were noted. Activity in the NV-01 group increased over the study period compared to placebo (P = 0.063) and the difference between the groups for change in activity over the time period 9am-5pm (8 hours) was significant (P = 0.006).
These pilot data demonstrate a positive analgesic effect of anti-NGF antibody in dogs suffering from chronic pain. The magnitude of the effect appeared identical to that expected with an NSAID.
除了非甾体抗炎药外,迫切需要经证实有效的药物来治疗犬类退行性关节病(DJD)疼痛。抗神经生长因子(NGF)抗体在啮齿动物模型和患有DJD的人类中具有镇痛作用。这项初步研究旨在评估一种新型犬源化抗NGF抗体(NV - 01)治疗犬类DJD疼痛的疗效。在一项随机、平行组、分层、双盲、安慰剂对照的原则性临床初步研究设计中,26只患有DJD的犬在第0天(D0)接受NV - 01(200 mcg/kg静脉注射)或安慰剂。除了客观的加速度测量外,主人在D0、D14和D28完成临床计量工具(特定客户结果测量[CSOM]、犬简短疼痛量表[CBPI]和犬类利物浦骨关节炎指数[LOAD])。对CBPI子量表(疼痛严重程度[PS]和疼痛干扰[PI])、CSOM和LOAD评分在组内和组间随时间的变化进行评估。应用公认的成功/失败标准并比较组间的成功情况。
NV - 01组的CBPI PS和PI评分显著改善(PS:D0 - 14,P = 0.012;D0 - 28,P = 0.019;PI:D0 - 14,P = 0.012;D0 - 28,P = 0.032),而安慰剂组没有改善。CSOM评分显示出类似的模式,在D14和D28组内变化有显著差异(分别为P = 0.038和P = 0.009),并且在D28成功的情况显著更多(P = 0.047)。NV - 01组的LOAD评分显著改善(D0 - 14,P = 0.004;D0 - 28,P = 0.002),而安慰剂组没有改善。在D14(P = 0.014)和D28(P = 0.033)时,两组间LOAD评分的变化有显著差异。未观察到副作用。与安慰剂相比,NV - 01组在研究期间的活动增加(P = 0.063),并且在上午9点至下午5点(8小时)期间两组间活动变化的差异显著(P = 0.006)。
这些初步数据表明抗NGF抗体对患有慢性疼痛的犬具有积极的镇痛作用。该作用的程度似乎与非甾体抗炎药预期的相同。