Dataset Information

Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis.

ABSTRACT:

Objective

To determine the effect of glucosamine, chondroitin, or the two in combination on joint pain and on radiological progression of disease in osteoarthritis of the hip or knee. Design Network meta-analysis. Direct comparisons within trials were combined with indirect evidence from other trials by using a Bayesian model that allowed the synthesis of multiple time points.

Main outcome measure

Pain intensity. Secondary outcome was change in minimal width of joint space. The minimal clinically important difference between preparations and placebo was prespecified at -0.9 cm on a 10 cm visual analogue scale.

Data sources

Electronic databases and conference proceedings from inception to June 2009, expert contact, relevant websites. Eligibility criteria for selecting studies Large scale randomised controlled trials in more than 200 patients with osteoarthritis of the knee or hip that compared glucosamine, chondroitin, or their combination with placebo or head to head. Results 10 trials in 3803 patients were included. On a 10 cm visual analogue scale the overall difference in pain intensity compared with placebo was -0.4 cm (95% credible interval -0.7 to -0.1 cm) for glucosamine, -0.3 cm (-0.7 to 0.0 cm) for chondroitin, and -0.5 cm (-0.9 to 0.0 cm) for the combination. For none of the estimates did the 95% credible intervals cross the boundary of the minimal clinically important difference. Industry independent trials showed smaller effects than commercially funded trials (P=0.02 for interaction). The differences in changes in minimal width of joint space were all minute, with 95% credible intervals overlapping zero. Conclusions Compared with placebo, glucosamine, chondroitin, and their combination do not reduce joint pain or have an impact on narrowing of joint space. Health authorities and health insurers should not cover the costs of these preparations, and new prescriptions to patients who have not received treatment should be discouraged.

SUBMITTER: Wandel S

PROVIDER: S-EPMC2941572 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVE:Osteoarthritis (OA) of the knee causes significant morbidity and current medical treatment is limited to symptom relief, while therapies able to slow structural damage remain elusive. This study was undertaken to evaluate the effect of glucosamine and chondroitin sulfate (CS), alone or in combination, as well as celecoxib and placebo on progressive loss of joint space width (JSW) in patients with knee OA. METHODS:A 24-month, double-blind, placebo-controlled study, conducted at 9 sites in the United States as part of the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), enrolled 572 patients with knee OA who satisfied radiographic criteria (Kellgren/Lawrence [K/L] grade 2 or grade 3 changes and JSW of at least 2 mm at baseline). Patients with primarily lateral compartment narrowing at any time point were excluded. Patients who had been randomized to 1 of the 5 groups in the GAIT continued to receive glucosamine 500 mg 3 times daily, CS 400 mg 3 times daily, the combination of glucosamine and CS, celecoxib 200 mg daily, or placebo over 24 months. The minimum medial tibiofemoral JSW was measured at baseline, 12 months, and 24 months. The primary outcome measure was the mean change in JSW from baseline. RESULTS:The mean JSW loss at 2 years in knees with OA in the placebo group, adjusted for design and clinical factors, was 0.166 mm. No statistically significant difference in mean JSW loss was observed in any treatment group compared with the placebo group. Treatment effects on K/L grade 2 knees, but not on K/L grade 3 knees, showed a trend toward improvement relative to the placebo group. The power of the study was diminished by the limited sample size, variance of JSW measurement, and a smaller than expected loss in JSW. CONCLUSION:At 2 years, no treatment achieved a predefined threshold of clinically important difference in JSW loss as compared with placebo. However, knees with K/L grade 2 radiographic OA appeared to have the greatest potential for modification by these treatments.

Project description: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.

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Project description:ObjectivesTo quantify the placebo effect of intraarticular injections for knee osteoarthritis in terms of pain, function, and objective outcomes. Factors influencing placebo effect were investigated.DesignMeta-analysis of randomized controlled trials; Level of evidence, 2. PubMed, Web of Science, Cochrane Library, and grey literature databases were searched on January 8, 2020, using the string: (knee) AND (osteoarthritis OR OA) AND (injections OR intra-articular) AND (saline OR placebo). The following inclusion criteria were used: double-blind, randomized controlled trials on knee osteoarthritis, including a placebo arm on saline injections. The primary outcome was pain variation. Risk of bias was assessed using the RoB 2.0 tool, and quality of evidence was graded following the GRADE (Grading of Recommendations Assessment, Development and Evaluation) guidelines.ResultsOut of 2,363 records, 50 articles on 4,076 patients were included. The meta-analysis showed significant improvements up to the 6-month follow-up: Visual Analogue Scale (VAS)-pain -13.4 mean difference (MD) (95% confidence interval [CI]: -21.7/-5.1; P < 0.001), Western Ontario and McMaster Osteoarthritis Index (WOMAC)-pain -3.3 MD (95% CI: -3.9/-2.7; P < 0.001). Other significant improvements were WOMAC-stiffness -1.1 MD (95% CI: -1.6/-0.6; P < 0.001), WOMAC-function -10.1 MD (95% CI: -12.2/-8.0; P < 0.001), and Evaluator Global Assessment -21.4 MD (95% CI: -29.2/-13.6; P < 0.001). The responder rate was 52% (95% CI: 40% to 63%). Improvements were greater than the "minimal clinically important difference" for all outcomes (except 6-month VAS-pain). The level of evidence was moderate for almost all outcomes.ConclusionsThe placebo effect of knee injections is significant, with functional improvements lasting even longer than those reported for pain perception. The high, long-lasting, and heterogeneous effects on the scales commonly used in clinical trials further highlight that the impact of placebo should not be overlooked in the research on and management of knee osteoarthritis.

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