Exploring reasons for the observed inconsistent trial reports on intra-articular injections with hyaluronic acid in the treatment of osteoarthritis: Meta-regression analyses of randomized trials

Mette Johansen, Henriette Bahrt, Roy D. Altman, Else M. Bartels, Carsten B. Juhl, Henning Bliddal, Hans Lund, Robin Christensen

Research output: Contribution to journalReview article

13 Scopus citations

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 (I2 = 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.

Original languageEnglish (US)
Pages (from-to)34-48
Number of pages15
JournalSeminars in Arthritis and Rheumatism
Volume46
Issue number1
DOIs
StatePublished - Aug 1 2016

Keywords

  • Bias
  • Efficacy
  • Hyaluronic acid
  • Inconsistency
  • Osteoarthritis
  • Pain

ASJC Scopus subject areas

  • Rheumatology
  • Anesthesiology and Pain Medicine

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