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 102 829 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. Systematic review registration PROSPERO number CRD42020213656 The guarantor (BRdC) is willing to examine all requests for the full dataset after a period of two years from the date of this publication.

中文翻译：

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非甾体抗炎药和阿片类药物治疗膝髋骨关节炎的有效性和安全性：网络荟萃分析

目的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，以尽可能有效和安全地使用这些药物。剂量。设计随机试验的系统评价和网络荟萃分析。数据来源 Cochrane Central Register of Controlled Trials (CENTRAL)、Medline、Embase、监管机构网站和 ClinicalTrials.gov，从开始到 2021 年 6 月 28 日。 选择研究的资格标准 以英文发表的随机试验，每组≥100 名患者评估 NSAID 、阿片类药物或扑热息痛（对乙酰氨基酚）治疗骨关节炎。结果和测量 预先指定的主要结果是疼痛。还评估了身体功能和安全结果。审查方法 两名审查员独立提取结局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分析的网络荟萃分析。效果估计是活性治疗和口服安慰剂之间的比较。结果 包括 102 829 名参与者的 192 项试验检查了 90 种不同的活性制剂或剂量（68 项用于 NSAID，19 项用于阿片类药物，3 项用于扑热息痛）。五种口服制剂（双氯芬酸 150 毫克/天，依托考昔 60 和 90 毫克/天，以及罗非昔布 25 和 50 毫克/天）比起最小的临床相关疼痛减轻有≥99% 的可能性更显着的治疗效果。局部使用双氯芬酸（70-81 和 140-160 毫克/天）的概率≥92.3%，并且所有阿片类药物的治疗效果比最小的临床相关疼痛减轻的概率≤53%。分别有 18.5%、0% 和 83.3% 的口服 NSAID、局部 NSAID 和阿片类药物因不良事件而退出的风险增加。分别有 29.8%、0% 和 89.5% 的口服非甾体抗炎药、局部非甾体抗炎药和阿片类药物发生任何不良事件的风险增加。由于不良事件 (51%) 和任何不良事件 (88%)，羟吗啡酮 80 毫克/天的退出风险最高。结论 依托考昔 60 毫克/天和双氯芬酸 150 毫克/天似乎是治疗骨关节炎患者疼痛和功能最有效的口服 NSAID。然而，这些治疗可能不适合有合并症或长期使用的患者，因为不良事件的风险略有增加。此外，发现双氯芬酸 150 毫克/天会增加因不良事件而退出的风险。外用双氯芬酸 70-81 毫克/天似乎是有效的，而且通常更安全，因为全身暴露减少和剂量较低，应考虑作为膝关节骨关节炎的一线药物治疗。无论制剂或剂量如何，阿片类药物治疗的临床益处都不会超过它可能对骨关节炎患者造成的危害。系统审查注册 PROSPERO 编号 CRD42020213656 保证人 (BRdC) 愿意在自本出版物发布之日起两年后审查对完整数据集的所有请求。外用双氯芬酸 70-81 毫克/天似乎是有效的，而且通常更安全，因为全身暴露减少和剂量较低，应考虑作为膝关节骨关节炎的一线药物治疗。无论制剂或剂量如何，阿片类药物治疗的临床益处都不会超过它可能对骨关节炎患者造成的危害。系统审查注册 PROSPERO 编号 CRD42020213656 保证人 (BRdC) 愿意在自本出版物发布之日起两年后审查对完整数据集的所有请求。外用双氯芬酸 70-81 毫克/天似乎是有效的，而且通常更安全，因为全身暴露减少和剂量较低，应考虑作为膝关节骨关节炎的一线药物治疗。无论制剂或剂量如何，阿片类药物治疗的临床益处都不会超过它可能对骨关节炎患者造成的危害。系统审查注册 PROSPERO 编号 CRD42020213656 保证人 (BRdC) 愿意在自本出版物发布之日起两年后审查对完整数据集的所有请求。