Mette Johansen1, Henriette Bahrt1, Roy D Altman2, Else M Bartels1, Carsten B Juhl3, Henning Bliddal1, Hans Lund4, Robin Christensen5. 1. The Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospitaler, Nordre Fasanvej 57, DK-2000, Copenhagen, Denmark. 2. Division of Rheumatology and Immunology, David Geffen School of Medicine, University of California, Los Angeles, CA 90024. 3. Department of Sports Science and Clinical Biomechanics, SEARCH, Research Unit for Muscusloskeletal Function and Physiotherapy, University of Southern Denmark, Odense, Denmark; Department of Orthopedics, Copenhagen University Hospital, Herlev and Gentofte Hospitaler, Copenhagen, Denmark. 4. Department of Sports Science and Clinical Biomechanics, SEARCH, Research Unit for Muscusloskeletal Function and Physiotherapy, University of Southern Denmark, Odense, Denmark; Centre for Evidence-Based Practice, Bergen University College, Bergen, Norway. 5. The Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospitaler, Nordre Fasanvej 57, DK-2000, Copenhagen, Denmark. Electronic address: Robin.Christensen@regionh.dk.
Abstract
OBJECTIVE: The aim was to identify factors explaining inconsistent observations concerning the efficacy of intra-articular hyaluronic acid compared to intra-articular sham/control, or non-intervention control, in patients with symptomatic osteoarthritis, based on randomized clinical trials (RCTs). METHODS: A systematic review and meta-regression analyses of available randomized trials were conducted. The outcome, pain, was assessed according to a pre-specified hierarchy of potentially available outcomes. Hedges׳s standardized mean difference [SMD (95% CI)] served as effect size. REstricted Maximum Likelihood (REML) mixed-effects models were used to combine study results, and heterogeneity was calculated and interpreted as Tau-squared and I-squared, respectively. RESULTS: Overall, 99 studies (14,804 patients) met the inclusion criteria: Of these, only 71 studies (72%), including 85 comparisons (11,216 patients), had adequate data available for inclusion in the primary meta-analysis. Overall, compared with placebo, intra-articular hyaluronic acid reduced pain with an effect size of -0.39 [-0.47 to -0.31; P < 0.001], combining very heterogeneous trial findings (I(2) = 73%). The three most important covariates in reducing heterogeneity were overall risk of bias, blinding of personnel and trial size, reducing heterogeneity with 26%, 26%, and 25%, respectively (Interaction: P ≤ 0.001). Adjusting for publication/selective outcome reporting bias (by imputing "null effects") in 24 of the comparisons with no data available reduced the combined estimate to -0.30 [-0.36 to -0.23; P < 0.001] still in favor of hyaluronic acid. CONCLUSION: Based on available trial data, intra-articular hyaluronic acid showed a better effect than intra-articular saline on pain reduction in osteoarthritis. Publication bias and the risk of selective outcome reporting suggest only small clinical effect compared to saline.
OBJECTIVE: The aim was to identify factors explaining inconsistent observations concerning the efficacy of intra-articular hyaluronic acid compared to intra-articular sham/control, or non-intervention control, in patients with symptomatic osteoarthritis, based on randomized clinical trials (RCTs). METHODS: A systematic review and meta-regression analyses of available randomized trials were conducted. The outcome, pain, was assessed according to a pre-specified hierarchy of potentially available outcomes. Hedges׳s standardized mean difference [SMD (95% CI)] served as effect size. REstricted Maximum Likelihood (REML) mixed-effects models were used to combine study results, and heterogeneity was calculated and interpreted as Tau-squared and I-squared, respectively. RESULTS: Overall, 99 studies (14,804 patients) met the inclusion criteria: Of these, only 71 studies (72%), including 85 comparisons (11,216 patients), had adequate data available for inclusion in the primary meta-analysis. Overall, compared with placebo, intra-articular hyaluronic acid reduced pain with an effect size of -0.39 [-0.47 to -0.31; P < 0.001], combining very heterogeneous trial findings (I(2) = 73%). The three most important covariates in reducing heterogeneity were overall risk of bias, blinding of personnel and trial size, reducing heterogeneity with 26%, 26%, and 25%, respectively (Interaction: P ≤ 0.001). Adjusting for publication/selective outcome reporting bias (by imputing "null effects") in 24 of the comparisons with no data available reduced the combined estimate to -0.30 [-0.36 to -0.23; P < 0.001] still in favor of hyaluronic acid. CONCLUSION: Based on available trial data, intra-articular hyaluronic acid showed a better effect than intra-articular saline on pain reduction in osteoarthritis. Publication bias and the risk of selective outcome reporting suggest only small clinical effect compared to saline.
Authors: Ninna K Senftleber; Sabrina M Nielsen; Jens R Andersen; Henning Bliddal; Simon Tarp; Lotte Lauritzen; Daniel E Furst; Maria E Suarez-Almazor; Anne Lyddiatt; Robin Christensen Journal: Nutrients Date: 2017-01-06 Impact factor: 5.717