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中华关节外科杂志(电子版) ›› 2024, Vol. 18 ›› Issue (04) : 484 -496. doi: 10.3877/cma.j.issn.1674-134X.2024.04.008

荟萃分析

糖皮质激素治疗膝骨关节炎疗效的网状Meta分析
李志文1, 李远志1, 李华2, 方志远2,()   
  1. 1. 100029 北京中医药大学第二临床医学院
    2. 100078 北京中医药大学东方医院
  • 收稿日期:2023-11-03 出版日期:2024-08-01
  • 通信作者: 方志远
  • 基金资助:
    北京中医药大学青年教师项目(2017-JYB-JS-98)

Network meta-analysis on efficacy of glucocorticoids in treatment of knee osteoarthritis

Zhiwen Li1, Yuanzhi Li1, Hua Li2, Zhiyuan Fang2,()   

  1. 1. The second clinical medical college of Beijing University of Traditional Chinese Medicine, Beijing 100029, China
    2. Dongfang Hospital of Beijing University of Traditional Chinese Medicine, Beijing 100078, China
  • Received:2023-11-03 Published:2024-08-01
  • Corresponding author: Zhiyuan Fang
引用本文:

李志文, 李远志, 李华, 方志远. 糖皮质激素治疗膝骨关节炎疗效的网状Meta分析[J]. 中华关节外科杂志(电子版), 2024, 18(04): 484-496.

Zhiwen Li, Yuanzhi Li, Hua Li, Zhiyuan Fang. Network meta-analysis on efficacy of glucocorticoids in treatment of knee osteoarthritis[J]. Chinese Journal of Joint Surgery(Electronic Edition), 2024, 18(04): 484-496.

目的

系统评价不同糖皮质激素(GC)联合(或不联合)透明质酸钠(HA)治疗膝骨关节炎(KOA)疗效的差异。

方法

应用计算机检索PubMed、Cochrane Library、Web of Science、ScienceDirect、中国知网(CNKI)、万方(Wanfang)、维普(VIP)、中国生物医学文献数据库(CBM),搜索有关膝关节内注射糖皮质激素治疗KOA的随机对照试验(RCT)文献,检索时限从建库至2023年5月。排除文献中发表重复、无法获取全文及研究数据不全或有误的,并由2位研究者从文献类型、研究对象、干预措施及结局指标方面对文献进行独立筛选。提取数据并评价偏倚风险,使用软件Review Manager 5.4和Stata 17进行网状Meta分析。

结果

共计检索相关文献2 098篇,最终纳入49个RCTs,包括13种用药方案,具体为HA、复方倍他米松(CB)、地塞米松(DXM)、醋酸甲泼尼龙(MPA)、曲安奈德(TA)、以注射用水或生理盐水为主要成分的安慰剂(PLA)、HA+CB、HA+PLA、HA+DXM、HA+MPA、HA+TA、CB+PLA、TA+PLA。治疗KOA过程中,网状Meta分析发现:(1)在提高有效率方面,排名前三位的用药方案分别是:HA+CB[与TA相比,比值比(OR)=22.13,95%(置信区间)CI (6.32,77.47)]、HA+TA[与TA相比,OR=20.39,95%CI (5.49,75.73)]、HA+DXM[与TA相比,OR=19.30,95%CI (4.77,78.20)];95% CI不包含1表明差异有统计学意义。(2)在降低西安大略和麦克马斯特大学骨关节炎指数(WOMAC)评分方面,排名前三位的用药方案为:DXM[与CB相比,均数差(MD)=-22.46,95%CI (-38.01,-6.90)]、HA+TA[与CB相比,MD=-13.87,95%CI (-27.38,-0.36)]、HA+CB[与CB相比,MD=-11.03,95%CI (-21.47,-0.60)];95% CI不包含0表明差异有统计学意义。(3)在降低膝关节疼痛视觉模拟量表(VAS)评分方面,排名前三位的用药方案为:HA+TA[与MPA相比,MD=-4.65,95%CI (-6.78,-2.51)]、CB+PLA[与MPA相比,MD=-2.60,95%CI (-4.69,-0.51)]、HA+CB[与MPA相比,MD=-2.50,95%CI (-4.06,-0.94)]。(4)在降低Lequesne指数方面,排名前三位的用药方案为:HA+TA[与PLA相比,MD=-6.72,95%CI (-9.33,-4.12)]、DXM[与PLA相比,MD=-5.60,95%CI (-8.80,-2.40)]、HA[与PLA相比, MD=-4.63,95%CI (-6.77,-2.49)]。

结论

在关节腔注糖皮质激素治疗膝骨关节炎的总体疗效方面,优先选择HA联合GC,其中HA+TA在治疗KOA整体评价方面上有较高的疗效。受限于纳入RCTs的数量及质量,该结论仍需更多高质量临床RCTs进一步验证。

Objective

To systematically evaluate the difference of therapeutic effects of different Glucocorticoid (GC) combined with or without sodium hyaluronate (HA) on knee osteoarthritis (KOA).

Methods

PubMed, Cochrane Library, Web of Science, Sciencedirect, China National Knowledge Infrastructure (CNKI), Wanfang , China Science and Technology Journal Database(VIP), and China Biology Medicine disc (CBM) were searched by computer, and the literatures about randomized controlled trial (RCT) of intra-articular injection of glucocorticoid in the treatment of knee arthritis were searched. The retrieval time ranged from establishment of the database to May 2023. The repetitive publication, lack of access to the full text and incomplete or incorrect research data were excluded, and two researchers screened the literature independently from the literature type, research object, intervention measures and outcome indicators.The data were extracted and the risk of bias was evaluated. Software ReviewManager5.4 and Stata17 were used for network meta-analysis.

Results

A total of 2098 related literatures were searched, and 49 RCTs were finally included, including 13 drug regimens, specifically HA, compound betamethasone (CB), dexamethasone (DXM), methylprednisolone acetate (MPA), triamcinolone acetonide (TA), placebo (PLA) with water for injection or normal saline as the main component, HA+CB, HA+PLA, HA+DXM, HA+MPA, HA+TA, CB+PLA, TA+PLA. In the process of the treatment of KOA, network meta-analysis showed results as follows :(1)for improving the effective rate, the top three drug regimens were HA+CB [compared with TA, odds ratio (OR)=22.13, 95% (confidence interval) CI (6.32, 77.47)], HA+TA [compared with TA, OR=20.39,95%CI (5.49, 75.73)], HA+DXM [compared with TA, OR=19.30,95%CI (4.77, 78.20)]; 95%CI does not contain 1, indicating that the difference is statistically significant.(2)For reducing the scores of Western Ontario and McMaster Universities osteoarthritis index (WOMAC), the top three drug regimens were DXM [compared with CB, the mean difference (MD) =-22.46% CI (- 38.01, -6.90)], HA+TA [compared with CB, MD=-13.87,95%CI (- 27.38, -0.36)], HA+CB [compared with CB, MD=-11.03,95%CI (- 21.47, -0.60)]; 95%CI does not contain 0 to indicate that the difference is statistically significant.(3)In terms of reducing the score of visual analogue scale (VAS), the top three medication schemes were HA+TA[compared with MPA, MD=-4.65, 95%CI (-6.78, -2.51)], CB+PLA[compared with MPA, MD=-2.60, 95%CI (-4.69, -0.51)], HA+CB[compared with MPA, MD=-2.50, 95%CI (-4.06, -0.94)].(4)In terms of reducing Lequesne index, the top three drug regimens were HA+TA[compared with PLA, MD=-6.72, 95%CI (-9.33, -4.12)], DXM[compared with PLA, MD=-5.60, 95%CI (-8.80, -2.40)], HA[compared with PLA, MD=-4.63,95%CI (-6.77,-2.49)].

Conclusion

HA combined with GC is preferred in the effectiveness of intra-articular injection of glucocorticoid in the treatment of knee osteoarthritis, among which HA+TA has a higher curative effect in the overall evaluation of KOA. Limited by the quantity and quality of RCTs, this conclusion still needs further verification by more high-quality clinical RCTs.

图1 文献筛选流程图
Figure 1 Screening process of literature
表1 纳入研究的基本特征
Table 1 Basic characteristics of included studies
第一作者
First author
发表年份
Year
样本量(例)
Sample number
干预措施
Intervention measures
疗程Time 结局指标 Outcomes
实验组 对照组 实验组 对照组
王志达9 2014 56 56 复方倍他米松+透明质酸钠 透明质酸钠+安慰剂 5周 ①④
张衍敬10 2016 47 47 复方倍他米松+透明质酸钠 透明质酸钠+安慰剂 5周 ①④
郝玉彬11 2013 50 50 复方倍他米松+透明质酸钠 透明质酸钠+安慰剂 5周 ①④
畅文丽12 2015 60 60 复方倍他米松+透明质酸钠 透明质酸钠+安慰剂 5周 ①④
王善正13 2021 58 58 复方倍他米松+透明质酸钠 复方倍他米松+安慰剂 1次 ②③
杨勋能14 2018 40 40 复方倍他米松+透明质酸钠 复方倍他米松 5周 ②③
李志军15 2020 64 64 复方倍他米松+透明质酸钠 透明质酸钠 5周 ①③
李娜16 2020 35 35 复方倍他米松+透明质酸钠 透明质酸钠 5周
陈献锦17 2017 38 38 复方倍他米松+透明质酸钠 透明质酸钠 3周 ①③
袁定坤18 2019 54 54 复方倍他米松+透明质酸钠 透明质酸钠 5周
赵国强19 2012 25 25 复方倍他米松+透明质酸钠 透明质酸钠 5周 ①③
左松波20 2008 43 43 复方倍他米松+透明质酸钠 透明质酸钠 5周
杜立群21 2018 44 44 复方倍他米松+透明质酸钠 透明质酸钠 5周
王功腾22 2018 210 210 复方倍他米松+透明质酸钠 透明质酸钠 5周 ②③
张新磊23 2023 63 63 复方倍他米松+透明质酸钠 透明质酸钠 5周 ①②
冯美杰24 2012 33 20 复方倍他米松+透明质酸钠 透明质酸钠 4周 ①③
刘大辉25 2020 44 44 复方倍他米松+透明质酸钠 透明质酸钠 3周
张立贵26 2011 29 28 复方倍他米松+透明质酸钠 透明质酸钠 8周
24 复方倍他米松
王小磊27 2011 50 50 地塞米松+透明质酸钠 透明质酸钠 5周
50 地塞米松 5周
Maia 28 2019 16 16 地塞米松+透明质酸钠 透明质酸钠 1次
12 地塞米松
廖黎黎29 2022 30 30 地塞米松+透明质酸钠 透明质酸钠 3周
张燕30 2014 60 58 地塞米松+透明质酸钠 透明质酸钠 15周
徐献信31 2015 54 54 地塞米松+透明质酸钠 透明质酸钠 5周
刘春元32 2012 47 49 地塞米松+透明质酸钠 透明质酸钠 5周
郑清山33 2018 53 53 曲安奈德+透明质酸钠 透明质酸钠 5周 ①③
Campos 34 2013 52 52 曲安奈德+透明质酸钠 透明质酸钠 1次 ②③④
魏建峰35 2012 41 41 曲安奈德+透明质酸钠 透明质酸钠 8周
陈立36 2021 50 50 曲安奈德+透明质酸钠 透明质酸钠 5周
宋洁37 2010 50 43 曲安奈德+透明质酸钠 透明质酸钠 5周
李前程38 2023 49 49 曲安奈德+透明质酸钠 透明质酸钠 5周 ①②
于新39 2018 60 46 曲安奈德+透明质酸钠 透明质酸钠 3周
de Campos 40 2013 52 52 曲安奈德+透明质酸钠 曲安奈德 ②③④
Hangody 41 2018 149/150 69 曲安奈德/透明质酸钠 安慰剂 1次
Raynauld 42 2003 33 33 曲安奈德 安慰剂 2年 ②③
Mendes 43 2019 35 35 曲安奈德 安慰剂 1次
McAlindon 44 2017 70 70 曲安奈德 安慰剂 24周
Gaffney 45 1995 42 42 曲安奈德 安慰剂 1次
Yavuz 46 2012 30 30 曲安奈德 安慰剂 1次
Skwara 47 2009 30 30 曲安奈德 透明质酸钠 1次 ③④
杨藕罗48 2005 30 30 曲安奈德 透明质酸钠 5周 ①④
Skwara 49 2009 21 21 曲安奈德 透明质酸钠 5周 ③④
曹宇虎50 2012 43 42 曲安奈德 透明质酸钠 5周
Jones 51 1995 27 29 曲安奈德+安慰剂 透明质酸钠 5周
赵良虎52 2015 50 50 复方倍他米松 透明质酸钠 5周
柳成行53 2017 100 100 复方倍他米松 透明质酸钠 5周
Yavuz 46 2012 30 30 复方倍他米松 醋酸甲泼尼龙 1次
Lomonte 54 2015 50 50 醋酸甲泼尼龙 曲安奈德 1次 ②③
Tasciotaoglu 55 2003 27 28 醋酸甲泼尼龙 透明质酸钠 3周 ③④
Bisicchia 56 2016 75 75 醋酸甲泼尼龙 透明质酸钠 2周 ②③
招淑珠57 2019 33 33 地塞米松 复方倍他米松 1次 ②④
图2 纳入研究的偏倚风险评价
Figure 2 Risk assessment of bias in include studies
图3 各结局指标网状关系图 注:HA-透明质酸钠;CB-复方倍他米松;DXM-地塞米松;TA-曲安奈德PLA-安慰剂;MPA-醋酸甲泼尼龙;HA+CB-透明质酸钠+复方倍他米松;HA+PLA-透明质酸钠+安慰剂;HA+DXM-透明质酸钠+地塞米松;HA+MPA-透明质酸钠+醋酸甲泼尼龙;HA+TA-透明质酸钠+曲安奈德;CB+PLA-复方倍他米松+安慰剂;TA+PLA-曲安奈德+安慰剂
Figure 3 Network diagram of each outcome indicators Note: HA- hyaluronic acid; CB-compound betamethasone; DXM-dexamethasone; TA-triamcinolone acetonide; PLA-placebo; MPA-methylprednisolone acetate; HA+CB-hyaluronic acid+compound betamethasone; HA+PLA-hyaluronic acid+placebo; HA+DXM-hyaluronic acid+dexamethasone; HA+MPA-hyaluronic acid+methylprednisolone acetate;HA+TA-hyaluronic acid+triamcinolone acetonide; CB+PLA-compound betamethasone+placebo; TA+PLA-triamcinolone acetonide+placebo
图4 治疗有效率的网状Meta分析结果 注:单元格数据为治疗有效率比较的OR(95% CI),95% CI不包含1表明差异有统计学意义;当OR>1时表明列治疗方案优于行治疗方案,反之则列治疗方案劣于行治疗方案
Figure 4 Network meta-analysis of treatment effective rate Note: The cell data is the OR (95%CI) of the comparison of the effective rate of treatment, and the fact that 95%CI does not contain 1 indicates that the difference is statistically significant; when OR>1, the treatment regimen of column is better than row, otherwise, the treatment regimen of column is worse than row
表2 治疗有效率的节点劈裂法结果
Table 2 Node splitting method results of treatment effective
表3 WOMAC评分的节点劈裂法结果
Table 3 Node splitting method results of WOMAC score
图5 WOMAC(西安大略与麦克马斯特大学)评分的网状Meta分析 注:单元格数据为WOMAC评分比较的MD(95% CI),95% CI不包含0表明差异有统计学意义;当MD<0时表明列治疗方案优于行治疗方案,反之则列治疗方案劣于行治疗方案
Figure 5 Network meta-analysis of WOMAC(Western Ontario and McMaster Universities osteoarthritis index) score Note: The cell data is the MD (95%CI)of the scores of WOMAC score, and the fact that 95%CI does not contain 0 indicates that the difference is statistically significant; when OR<0, the treatment regimen of column is better than row, otherwise, the treatment regimen of column is worse than row
表4 VAS评分的节点劈裂法结果
Table 4 Node splitting method results of visual analogue scale
图6 VAS(视觉模拟评分)评分的网状Meta分析 注:单元格数据为VAS评分比较的MD(95% CI),95% CI不包含0表明差异有统计学意义;当MD<0时表明列治疗方案优于行治疗方案,反之则列治疗方案劣于行治疗方案
Figure 6 Network meta-analysis of VAS(visual analogue scale)score Note: The cell data is the MD (95%CI) of the score of visual analogue scale, and the fact that 95%CI does not contain 0 indicates that the difference is statistically significant; when OR<0, the treatment regimen of column is better than row, otherwise, the treatment regimen of column is worse than row
表5 Lequesne指数评分的节点劈裂法结果
Table 5 Node splitting method results of Lequesne index
图7 Lequesne指数评分的网状Meta分析 注:单元格数据为Lequesne评分比较的MD(95% CI),95% CI不包含0表明差异有统计学意义;当MD<0时表明列治疗方案优于行治疗方案,反之则列治疗方案劣于行治疗方案
Figure 7 Network meta-analysis of Lequesne index score Note: The cell data is the MD (95%CI) of the Lequesne index, and the fact that 95%CI does not contain 0 indicates that the difference is statistically significant; when OR<0, the treatment regimen of column is better than row, otherwise, the treatment regimen of column is worse than row
表6 网状Meta分析SUCRA值和排序
Table 6 SUCRA values and rank of network Meta-analysis
图8 4个结局指标比较-校正漏斗图
Figure 8 Inverted funnel plot of four outcome indicators
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