Nerve growth factor blockade for the management of osteoarthritis pain: what can we learn from clinical trials and preclinical models?
Nerve growth factor blockade for the management of osteoarthritis pain: what can we learn from clinical trials and preclinical models?
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DOI：
10.1097/bor.0000000000000354
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发表时间：
2017-01
影响因子：
5.1
通讯作者：
Malfait AM
中科院分区：
文献类型：
--
作者：
Miller RE;Block JA;Malfait AM
抗ngf抗体在治疗骨关节炎（OA）疼痛方面具有巨大的潜力，但临床试验显示其严重的不良反应尚不完全清楚。本综述讨论了临床试验结果以及评估实验性OA中NGF阻断的临床前研究，以便为未来的研究提供见解。系统评价显示，包括tanezumab在内的抗ngf治疗在改善疼痛和功能方面是有效的，但严重的不良事件，包括快速进展的OA和骨坏死，导致暂停试验，直到最近才取消。在过去的一年中，临床前测试揭示了NGF阻断对OA实验模型疼痛行为和关节结构的影响。与临床试验结果相似，这些实验动物研究证实了NGF阻断剂的镇痛作用。有趣的是，一些动物研究表明，治疗对关节完整性有不利影响，特别是在疾病早期开始治疗时，此时关节损伤为轻度至中度。NGF阻断仍然是治疗OA疼痛的一种有希望的新方法，但实际的益处和风险仍有待充分阐明。临床前模型可能表明，在限制副作用的同时，可以最好地服务于患者群体，但未来的工作应进一步研究益处和不良副作用的机制。
Anti-NGF antibodies hold tremendous potential for the management of osteoarthritis (OA) pain, but clinical trials have revealed serious adverse effects that are incompletely understood. This review discusses clinical trial results along with preclinical studies that have assessed NGF blockade in experimental OA, in order to provide insight for future studies. Systematic reviews have revealed that anti-NGF therapy, including tanezumab, is efficacious in improving pain and function, but serious adverse events, including rapidly progressive OA and osteonecrosis, resulted in a moratorium on trials that was only recently lifted. Within the past year, preclinical testing has revealed effects of NGF blockade on both pain behaviors and joint structure in experimental models of OA. Similar to clinical trial results, these studies in laboratory animals demonstrated analgesic efficacy of NGF blockade. Interestingly, several animal studies have suggested detrimental effects on joint integrity as a result of treatment, particularly when treatment is started early in the disease, when joint damage is mild to moderate. NGF blockade continues to represent a promising new approach for the treatment of OA pain, but the actual benefits and risks remain to be fully elucidated. Preclinical models may suggest patient populations that could be best served while limiting side effects, but future work should further investigate the mechanisms of benefits and unwanted side effects.