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Meta-Analysis
. 2019 May;36(5):1085-1099.
doi: 10.1007/s12325-019-00921-w. Epub 2019 Mar 16.

Efficacy of Chondroitin Sulfate in Patients with Knee Osteoarthritis: A Comprehensive Meta-Analysis Exploring Inconsistencies in Randomized, Placebo-Controlled Trials

Germain Honvo  1   2 , Olivier Bruyère  3   4 , Anton Geerinck  3   4 , Nicola Veronese  5 , Jean-Yves Reginster  3   6
Affiliations
Meta-Analysis

Efficacy of Chondroitin Sulfate in Patients with Knee Osteoarthritis: A Comprehensive Meta-Analysis Exploring Inconsistencies in Randomized, Placebo-Controlled Trials

Germain Honvo et al. Adv Ther. 2019 May.

Abstract

Introduction: 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.

Methods: 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 tau2 and I2 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.

Results: The inclusion criteria yielded 18 trials. Overall, CS significantly but inconsistently reduced pain (SMD: - 0.63; 95% CI: - 0.91, - 0.35; I2 = 94%) and improved function (SMD: - 0.82; 95% CI: - 1.31, - 0.33; I2 = 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; I2 = 75%) and function (SMD: - 0.33; 95% CI: - 0.47, - 0.20; I2 = 53%, p = 0.07) compared with the other preparations (SMDPain: - 0.08; 95% CI: - 0.19, + 0.02; I2 = 20%; SMDFunction: - 0.18; 95% CI: - 0.36, +0.01; I2 = 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: rS = 0.93; LI: rS = 0.86; p < 0.05). Ultimately, there was no residual heterogeneity in the CS effects when the smallest studies were removed from the analyses.

Conclusion: 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.

Keywords: Chondroitin sulfate; Functional status; Meta-analysis; Osteoarthritis; Pain; Rheumatology.

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Figures

Fig. 1
Fig. 1
Flow chart of the review
Fig. 2
Fig. 2
Meta-analysis of the effect of chondroitin sulfate on pain in patients with osteoarthritis, including all eligible trials
Fig. 3
Fig. 3
Meta-analysis of the effect of chondroitin sulfate on the Lequesne index in patients with osteoarthritis, including all eligible trials
Fig. 4
Fig. 4
Funnel plots for pain (a) and the Lequesne index (b), using data from the primary meta-analyses including all eligible trials, stratified according to the risk of attrition bias in studies
See this image and copyright information in PMC

References

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