加拿大多伦多圣迈克尔医院Bruno R da Costa团队对粘液补充剂治疗膝骨关节炎的效果进行了系统回顾和荟萃分析。这一研究成果发表在2022年7月6日出版的《英国医学杂志》上。

为了评估粘液补充剂对膝骨关节炎患者疼痛和功能的有效性和安全性，研究组在Medline、Embase和Cochrane中央对照试验登记册（Central）数据库中检索从建库到2021年9月11日的文献，未发表的试验从灰色文献和试验登记处确定，筛选出比较粘液补充剂与安慰剂或不干预治疗膝骨关节炎的随机试验，并进行系统回顾和荟萃分析。

预先确定的主要结局是疼痛强度。次要结局是功能和严重不良事件。疼痛和功能以标准化平均差（SMD）进行分析。预先指定的最小临床重要组间差异为−0.37 SMD。严重不良事件作为相对风险进行分析。

由两名评审员独立提取相关数据，并使用Cochrane偏倚风险工具评估试验的偏倚风险。预定义的主要分析仅基于每组≥100名参与者的大型安慰剂对照试验。通过随机效应荟萃分析模型获得汇总结果。在随机效应模型下进行累积荟萃分析和试验序列分析。

169项试验提供了21163名随机参与者的数据。在疼痛和功能方面观察到小研究效应和发表偏倚的证据。疼痛主要分析中的24个大型安慰剂对照试验（8997名随机参与者）表明，与安慰剂相比，补充粘液与疼痛强度的轻微降低有关，SMD为−0.08，95%置信区间的下限排除最小临床重要组间差异。

在100 mm视觉模拟刻度上，这种效应对应于疼痛评分的差异为−2.0mm。疼痛的试验序列分析表明，自2009年以来，有确凿证据表明粘液补充剂和安慰剂之间的临床等效性。对于功能也得出了类似的结论。基于对6462名随机参与者进行的15项大型安慰剂对照试验表明，与安慰剂相比，补充粘液后严重不良事件的风险在统计学上显著高于安慰剂（相对风险1.49）。

总之，强有力的结论性证据表明，与安慰剂相比，补充粘液可以轻微减轻膝骨关节炎疼痛，但其差异小于最小组间临床重要差异。同时，强有力的结论性证据表明，与安慰剂相比，补充粘液也会增加严重不良事件的风险。研究结果不支持广泛使用粘液补充剂治疗膝骨关节炎。

附：英文原文

Title: Viscosupplementation for knee osteoarthritis: systematic review and meta-analysis

Author: Tiago V Pereira, Peter Jüni, Pakeezah Saadat, Dan Xing, Liang Yao, Pavlos Bobos, Arnav Agarwal, Cesar A Hincapié, Bruno R da Costa

Issue&Volume: 2022/07/06

Abstract:

Objective To evaluate the effectiveness and safety of viscosupplementation for pain and function in patients with knee osteoarthritis.

Design Systematic review and meta-analysis of randomised trials.

Data sources Searches were conducted of Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to 11 September 2021. Unpublished trials were identified from the grey literature and trial registries.

Eligibility criteria for study selection Randomised trials comparing viscosupplementation with placebo or no intervention for knee osteoarthritis treatment.

Main outcome measures The prespecified primary outcome was pain intensity. Secondary outcomes were function and serious adverse events. Pain and function were analysed as standardised mean differences (SMDs). The prespecified minimal clinically important between group difference was 0.37 SMD. Serious adverse events were analysed as relative risks.

Methods Two reviewers independently extracted relevant data and assessed the risk of bias of trials using the Cochrane risk of bias tool. The predefined main analysis was based only on large, placebo controlled trials with ≥100 participants per group. Summary results were obtained through a random effects meta-analysis model. Cumulative meta-analysis and trial sequential analysis under a random effects model were also performed.

Results 169 trials provided data on 21163 randomised participants. Evidence of small study effects and publication biases was observed for pain and function (Egger’s tests with P<0.001 and asymmetric funnel plots). Twenty four large, placebo controlled trials (8997 randomised participants) included in the main analysis of pain indicated that viscosupplementation was associated with a small reduction in pain intensity compared with placebo (SMD 0.08, 95% confidence interval 0.15 to 0.02), with the lower bound of the 95% confidence interval excluding the minimal clinically important between group difference. This effect corresponds to a difference in pain scores of 2.0 mm (95% confidence interval 3.8 to 0.5 mm) on a 100 mm visual analogue scale. Trial sequential analysis for pain indicated that since 2009 there has been conclusive evidence of clinical equivalence between viscosupplementation and placebo. Similar conclusions were obtained for function. Based on 15 large, placebo controlled trials on 6462 randomised participants, viscosupplementation was associated with a statistically significant higher risk of serious adverse events than placebo (relative risk 1.49, 95% confidence interval 1.12 to 1.98).

Conclusion Strong conclusive evidence indicates that viscosupplementation leads to a small reduction in knee osteoarthritis pain compared with placebo, but the difference is less than the minimal clinically important between group difference. Strong conclusive evidence indicates that viscosupplementation is also associated with an increased risk of serious adverse events compared with placebo. The findings do not support broad use of viscosupplementation for the treatment of knee osteoarthritis.

DOI: 10.1136/bmj-2022-069722

Source: https://www.bmj.com/content/378/bmj-2022-069722