小柯机器人

加拿大多伦多圣米歇尔医院Bruno R da Costa团队研究了非甾体抗炎药和阿片类药物治疗膝关节和髋关节骨关节炎的有效性和安全性。该研究于2021年10月12日发表于《英国医学杂志》上。

为了评估不同制剂和剂量的非甾体抗炎药（NSAIDs）、阿片类药物和扑热息痛对膝关节和髋关节骨关节炎疼痛和身体功能的有效性和安全性，以使这些药物在尽可能低的剂量下安全有效地使用，研究组在Cochrane中央对照试验注册中心（Central）、Medline、Embase等大型数据库中检索从建库至2021年6月28日的相关文献。

筛选出英文发表，评估NSAIDs、阿片类药物或扑热息痛（对乙酰氨基酚）治疗骨关节炎，每组超过100名患者的随机试验，并进行系统评价和网络荟萃分析。预先确定的主要结局是疼痛。还评估了身体功能和安全性结局。由两名审查员独立提取结果数据并评估纳入试验的偏倚风险。贝叶斯随机效应模型用于所有网络荟萃分析。疗效评估是积极治疗和口服安慰剂之间的比较。

192项临床试验共包括102829名参与者，检查了90种不同活性制剂或剂量的药物，其中68种为NSAIDs，19种为阿片类药物，3种为扑热息痛。五种口服制剂（双氯芬酸150 mg/d，依托考昔60和90 mg/d，罗非昔布25和50 mg/d）有≥99%的概率可获得比最小临床相关疼痛减轻更为显著的疗效。

外用双氯芬酸（70-81和140-160 mg/d）有≥92.3%的概率，所有阿片类药物都有≤53%的概率可获得比最小临床相关疼痛减轻更为显著的疗效。分别有18.5%、0%和83.3%的口服NSAIDs、局部NSAIDs和阿片类药物因不良事件而中断治疗。口服NSAIDs、局部NSAIDs和阿片类药物的不良事件风险分别为29.8%、0%和89.5%。羟吗啡酮80 mg/d因不良事件（51%）和任何不良事件（88%）而中断治疗的风险最高。

研究结果表明，依托考昔60 mg/d和双氯芬酸150 mg/d似乎是治疗骨关节炎患者疼痛和功能最有效的口服非甾体抗炎药。此外，发现双氯芬酸150 mg/d因不良事件而退出的风险增加。双氯芬酸70-81 mg/d的外用似乎有效，且总体上安全，因为它减少了全身暴露和较低的剂量，应该被视为膝骨关节炎的一线药物治疗。阿片类药物无论是制剂还是剂量，用于治疗骨关节炎患者均是弊大于利。

附：英文原文

Title: Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis

Author: Bruno R da Costa, Tiago V Pereira, Pakeezah Saadat, Martina Rudnicki, Samir M Iskander, Nicolas S Bodmer, Pavlos Bobos, Li Gao, Henry Dan Kiyomoto, Thais Montezuma, Matheus O Almeida, Pai-Shan Cheng, Cesar A Hincapié, Roman Hari, Alex J Sutton, Peter Tugwell, Gillian A Hawker, Peter Jüni

Issue&Volume: 2021/10/12

Abstract:

Objective To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose.

Design Systematic review and network meta-analysis of randomised trials.

Data sources Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021.

Eligibility criteria for selecting studies Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis.

Outcomes and measures The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed.

Review methods Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo.

Results 192 trials comprising 102829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%).

Conclusions Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis.

DOI: 10.1136/bmj.n2321

Source: https://www.bmj.com/content/375/bmj.n2321

BMJ-British Medical Journal:《英国医学杂志》，创刊于1840年。隶属于BMJ出版集团，最新IF：93.333
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