Effects of hyaluronic acid combined with anti-inflammatory drugs compared with hyaluronic acid alone, in clinical trials and experiments in osteoarthritis: a systematic review and meta-analysis

Abstract

BackgroundThe objectives are to compare the efficacy of intra-articular hyaluronic acid (IA-HA) alone and in combination with anti-inflammatory drugs (IA-HA + AI), corticosteroids (CS) or non-steroidal anti-inflammatory drugs (NSAIDs) in clinical trials and in vivo and in vitro studies of osteoarthritis (OA).MethodsData in the BIOSIS, CINAHL, Cochrane Library, EMBASE and Medline databases were collected and analyzed. Random effects models were used to compute the effect size (ES) of the mean difference in pain reduction scores from baseline and the relative risk (RR) of adverse events. The ES of histological scores in vivo and cartilage metabolism in vitro were also calculated. We conducted sensitivity analysis of blinding and intention-to-treat (ITT), compared IA-HA combined with CS vs. IA-HA alone in trials, and compared the effects of HA + AI vs. AI alone in vitro, including anabolic and catabolic gene expression.ResultsThirteen out of 382 papers were included for data analysis. In clinical trials, the ES of pain reduction scores within the 1st month was −4.24 (−6.19, −2.29); 2nd–12th month, −1.39 (−1.95, −0.82); and within one year, −1.63 (−2.19, −1.08), favoring IA-HA + AI (P < 0.001). The ES of RR was 1.08 (0.59, 1.98), and histological scores was 1.38 (−0.55, 3.31). The ES of anabolic gene expression was 1.22 (0.18, 2.25), favoring HA alone (P < 0.05); catabolic gene expression was 0.74 (−0.44, 1.53), favoring HA alone; and glycosaminoglycans remaining was −2.45 (−5.94, 1.03).ConclusionsIA-HA + AI had greater efficacy for pain relief than IA-HA alone within a one-year period. However, HA + AI down-regulated the ACAN gene when compared with HA alone in vitro.

Efficacy of combination therapy of Hyaluronic acid and Methylprednisolon verses Hyaluronic acid single therapy in knee Osteoarthritis : A comparative study

“…They found that, Intra-articular Hyaluronic acid and anti-inflammatory drugs had greater efficacy for pain relief than Intra-articular Hyaluronic acid alone. 10 In our study, we used Methyl prednisolone with Hyaluronic acid and also found better efficacy of combination therapy in terms of pain relief and function improvement.…”

Primary Human Chondrocytes Affected by Cigarette Smoke—Therapeutic Challenges

“…Thus, not only pain relief and suppression of inflammation should be addressed, but also cartilage repair. Recent reports have investigated the combined effects of HA and anti-inflammatory drugs (CSs or NSAIDs) [66,67] in order to develop more effective OA treatments. We evaluated the combined effects of HA with low concentrations of Dex and therapeutic concentrations of Dic or Ace on CSE-impaired chondrocytes.…”

Shea Nut Oil Extracts Enhance the Intra-Articular Sodium Hyaluronate Effectiveness on Surgically Induced OA Progression in Rats

“…Although the protective potential of oral SNO supplementation differs from that of IAHA in many aspects (route, dose frequency, and mechanism of action). But the combination of both therapeutic models, like IA corticosteroid/anti-inflammatory drugs combined with IAHA, can lead to significant improvement of the clinical outcome of either agent alone [30]; this however only provides short duration, and is not feasible for persisting injection. Therefore, we sought to determine the role of oral SNO as an adjuvant in combination with IAHA injections and compare the effectiveness in the OA rat model.…”