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抗神经生长因子单克隆抗体治疗在治疗髋或膝骨关节炎方面是否有潜力取代非甾体抗炎药和阿片类药物?一项随机对照试验的系统评价。

Does anti-nerve growth factor monoclonal antibody treatment have the potential to replace nonsteroidal anti-inflammatory drugs and opioids in treating hip or knee osteoarthritis? A systematic review of randomized controlled trials.

作者信息

Zhao Di, Zeng Ling-Feng, Liang Gui-Hong, Pan Jian-Ke, Luo Ming-Hui, Han Yan-Hong, Liu Jun, Yang Wei-Yi

机构信息

The Second Clinical School of Guangzhou University of Chinese Medicine, Guangzhou, China.

Bone and Joint Research Team of Degeneration and Injury, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China.

出版信息

EFORT Open Rev. 2022 Jul 5;7(7):470-480. doi: 10.1530/EOR-21-0103.

Abstract

PURPOSE

Considering the adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids for treating osteoarthritis (OA), development of drugs that are more effective and better tolerated than existing treatments is urgently needed. This systematic review aimed to evaluate the efficacy and safety of anti-nerve growth factor (NGF) monoclonal antibodies vs active comparator therapy, such as NSAIDs and oxycodone, in treating hip or knee OA.

METHODS

Databases were comprehensively searched for randomized controlled trials (RCTs) published before January 2022. Efficacy and safety outcomes were assessed.

RESULTS

Six RCTs that included 4325 patients were identified. Almost all the RCTs indicated that moderate doses of anti-NGF monoclonal antibody treatment significantly improved efficacy outcomes based on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score, the WOMAC physical function score and the Patient's Global Assessment compared with those of the active comparator. At least half of the RCTs indicated that the incidence of severe adverse events, withdrawals due to adverse events (AEs) and total joint replacement were not significantly different between anti-NGF monoclonal antibody treatment and active comparator therapy, but the outcomes of some studies may have been limited by a short duration of follow-up. Most RCTs suggested that anti-NGF monoclonal antibody treatment had a lower incidence of gastrointestinal and cardiovascular AEs. However, the majority of RCTs reported a higher incidence of abnormal peripheral sensation with anti-NGF monoclonal antibody treatment. Furthermore, the higher incidence of rapidly progressive osteoarthritis (RPOA) with anti-NGF monoclonal antibody treatment should also not be overlooked, and the identification of patient characteristics that increase the risk of RPOA is critical in further studies.

CONCLUSION

Based on the current research evidence, anti-NGF monoclonal antibodies are not yet a replacement for analgesic drugs such as NSAIDs but might be a new treatment option for hip or knee OA patients who are intolerant or unresponsive to nonopioid or opioid treatment. Notably, however, considering the inconsistency and inconclusive evidence on the safety outcomes of recent studies, more research is needed, and long-term follow-up is required.

摘要

目的

鉴于非甾体抗炎药(NSAIDs)和阿片类药物在治疗骨关节炎(OA)时存在不良反应,迫切需要开发比现有治疗方法更有效且耐受性更好的药物。本系统评价旨在评估抗神经生长因子(NGF)单克隆抗体与活性对照疗法(如NSAIDs和羟考酮)在治疗髋或膝OA方面的疗效和安全性。

方法

全面检索截至2022年1月发表的随机对照试验(RCT)。评估疗效和安全性结果。

结果

共纳入6项RCT,涉及4325例患者。几乎所有RCT均表明,与活性对照相比,中等剂量的抗NGF单克隆抗体治疗基于西安大略和麦克马斯特大学骨关节炎指数(WOMAC)疼痛评分、WOMAC身体功能评分和患者总体评估,显著改善了疗效结果。至少一半的RCT表明,抗NGF单克隆抗体治疗与活性对照疗法相比,严重不良事件、因不良事件(AE)导致的停药和全关节置换的发生率无显著差异,但部分研究结果可能因随访时间短而受到限制。大多数RCT表明,抗NGF单克隆抗体治疗的胃肠道和心血管AE发生率较低。然而,大多数RCT报告抗NGF单克隆抗体治疗的外周感觉异常发生率较高。此外,抗NGF单克隆抗体治疗快速进展性骨关节炎(RPOA)的较高发生率也不应被忽视,在进一步研究中确定增加RPOA风险的患者特征至关重要。

结论

基于目前的研究证据,抗NGF单克隆抗体尚不能替代NSAIDs等镇痛药,但可能是对非阿片类或阿片类治疗不耐受或无反应的髋或膝OA患者的一种新治疗选择。然而,值得注意的是,考虑到近期研究安全性结果存在不一致和不确定性证据,需要更多研究,并进行长期随访。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0a6/9297056/7eecf76aa72c/EOR-21-0103fig1.jpg

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