Symptomatic efficacy of oral Chondroitin sulfate in knee osteoarthritls. A systematic review and meta-analysls of randomized, placebo-controlled trials
G. Honvo Osteoarthritis and Cartilage VOLUME 27, SUPPLEMENT 1, S498-S499, APRIL 01, 2019
Purpose: To determine whether Chondroitin Sulfate (CS) is effective in alleviating pain and improving functional status in patients with knee Osteoarthritis (OA). To determine whether brand of CS, risk of bias, dose of CS and duration of study explain inconsistencies in trials using CS for the symptomatic management of OA.
Methods: A systematic review of randomized, placebo-controlled trials was conducted, searching the databases Medline, CENTRAL and Scopus. Random-effect meta-analysis was performed, using the Tau2 and I2 statistics to assess heterogeneity. Both pain and the Lequesne index (LI), a composite index measuring pain and function, scores were expressed as Standardized Mean Differences (SMD) and 95% Cl. Heterogeneity was explored by stratifying the analyses according to pre-specified study level characteristics. For sensitivity analyses, the fixed-effect model was applied.
Results: The inclusion criteria yielded 18 trials. CS reduced pain (SMD:-0.63 (95%Cl:-0.91,-0.35)) although a high level of between-trial inconsistency was observed (I2:94%). When limiting the analysis to studies at low risk of bias, the reduction in pain remained significant (SMD:-0.18 (95%Cl:-0.25,-0.12)). Studies conducted with the IBSA-Genevrier CS showed a greater reduction in pain (SMD:-0.25 (95%Cl:-0.34,-0.16)) compared to the other preparations (SMD:-0.08 (95%Cl:-0.19,+0.02)).The presence of NSAIDs as a rescue medication did not alter the effect of CS on pain (SMD:-0.15 (95%Cl:-0.25,-0.06)) compared to the effect observed when no NSAIDs were given (SMD:-0.22 (95%Cl:-0.31,-0.12)). The 800mg daily dose of CS (SMD:-0.19 (95%CI:-0.28,-0.10)) was as effective as the doses ranging from 1000mg to 2000mg daily (SMD:-0.17 (95%Cl:-0.28,-0.07)). A significant reduction in pain was seen in studies lasting 3 months (SMD:-0.40 (95%Cl:-0.59,-0.22)), or 4-12 months (SMD:-0.20 (95%Cl:-0.30,-0.11)) but was no longer significant in the few (n=3) studies of > 12 months (SMD:-0.08 (95%Cl:-0.19,+0.04)). Results were consistent when LI was assessed with a SMD of -0.82 (95%CI:-1.31,-0.33) and a I2 of 95% in all studies and a SMD of -0.28 (95%Cl:-0.39,-0.18) in studies at low risk of bias. Studies conducted with the IBSA-Genevrier CS also generated a greater effect on LI (SMD:-0.33 (95%Cl:-0.47,-0.20)) compared to the other CS preparations (SMD:-0.18 (95%Cl:-0.36,+0.01)). Studies with (SMD:-0.28 (95%CI -0.48,-0.10)) or without (SMD:-0.29 (95%Cl:-0.42,-0.15)) NSAIDs given as rescue medications showed a similar effect on LI. CS was effective on LI at doses of 800mg/day (SMD:-0.23 (95%Cl:-0.39,-0.07)) or above (SMD:-0.32 (95%CI:-0.47,-0.18)). LI was improved in studies of 3-month duration (SMD -0.45 (95%Cl:-0.64,-0.26)) or in studies lasting 4-12 months (SMD:-0.20 (95%Cl:-0.33,-0.07)).
Conclusions: This new meta-analysis suggests that CS provides a moderate benefit on pain and function in knee OA. The pharmaceuticalgrade preparation marketed by IBSA-Genevrier generates greater benefits than the other CS. A daily dose of 800mg is as effective as higher doses and the effect is observed in studies of 3-month duration as well as in studies lasting up to 12 months, with or without NSAIDs given as rescue medications.