Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium.
Adv Ther. 2019 May;36(5):1085-1099. doi: 10.1007/s12325-019-00921-w. Epub 2019 Mar 16.
There are some controversies about treatment modalities in osteoarthritis (OA), including chondroitin sulfate (CS). The objective of this study was to determine whether CS is effective at alleviating pain and improving function in patients with knee OA and to identify the factors that explain inconsistencies in clinical trial results.
We conducted a systematic review of randomized, placebo-controlled trials, searching the databases Medline, Cochrane central register for controlled trials and Scopus. Random effects meta-analysis was then performed, using tau and I statistics to assess heterogeneity. The pain and Lequesne index (LI) scores were expressed as standardized mean differences (SMDs), with a 95% confidence interval (CI). Heterogeneity was explored by stratifying the analyses according to pre-specified study-level characteristics and assessing the sources of funnel plot asymmetry.
The inclusion criteria yielded 18 trials. Overall, CS significantly but inconsistently reduced pain (SMD: - 0.63; 95% CI: - 0.91, - 0.35; I = 94%) and improved function (SMD: - 0.82; 95% CI: - 1.31, - 0.33; I = 95%). When limiting the analysis to studies with a low risk of bias, the pharmaceutical grade CS of IBSA origin showed a greater reduction in pain (SMD: - 0.25; 95% CI: - 0.34, - 0.16; I = 75%) and function (SMD: - 0.33; 95% CI: - 0.47, - 0.20; I = 53%, p = 0.07) compared with the other preparations (SMD: - 0.08; 95% CI: - 0.19, + 0.02; I = 20%; SMD: - 0.18; 95% CI: - 0.36, +0.01; I = 0%). Assessing funnel plot asymmetry in the studies with a low risk of bias, we found strong correlations between the treatment effects and study size (pain: r = 0.93; LI: r = 0.86; p < 0.05). Ultimately, there was no residual heterogeneity in the CS effects when the smallest studies were removed from the analyses.
This new meta-analysis suggests that CS provides a moderate benefit for pain and has a large effect on function in knee OA, however with large inconsistency. The risks of bias, brand and study size were the factors explaining heterogeneity among the clinical trial results.
在骨关节炎（OA）的治疗方法中存在一些争议，包括硫酸软骨素（CS）。本研究的目的是确定 CS 是否能有效缓解膝骨关节炎患者的疼痛和改善功能，并确定解释临床试验结果不一致的因素。
我们对随机、安慰剂对照试验进行了系统评价，检索了 Medline、Cochrane 对照试验中心注册库和 Scopus 数据库。然后使用 tau 和 I 统计量评估异质性，进行随机效应荟萃分析。疼痛和 Lequesne 指数（LI）评分表示为标准化均数差（SMD），置信区间（CI）为 95%。根据预先设定的研究水平特征对分析进行分层，并评估漏斗图不对称的来源，以探索异质性。
纳入标准产生了 18 项试验。总体而言，CS 显著但不一致地减轻了疼痛（SMD：-0.63；95%CI：-0.91，-0.35；I=94%）和改善了功能（SMD：-0.82；95%CI：-1.31，-0.33；I=95%）。当将分析限制为偏倚风险较低的研究时，IBSA 来源的药用级 CS 显示出更大的疼痛缓解（SMD：-0.25；95%CI：-0.34，-0.16；I=75%）和功能改善（SMD：-0.33；95%CI：-0.47，-0.20；I=53%，p=0.07），与其他制剂相比（SMD：-0.08；95%CI：-0.19，+0.02；I=20%；SMD：-0.18；95%CI：-0.36，+0.01；I=0%）。在偏倚风险较低的研究中评估漏斗图不对称性时，我们发现治疗效果与研究规模之间存在很强的相关性（疼痛：r=0.93；LI：r=0.86；p<0.05）。最终，当从分析中删除最小的研究时，CS 效应的异质性消失。
这项新的荟萃分析表明，CS 对膝骨关节炎患者的疼痛有中度益处，对功能有较大影响，但存在较大的不一致性。偏倚风险、品牌和研究规模是解释临床试验结果异质性的因素。
