Intra-Articular Hyaluronic Acid in the Symptomatic Treatment of Knee Osteoarthritis: A Meta-Analysis of Single-Injection Products

Abstract

Background Viscosupplementation of the synovial fluid with intra-articular hyaluronic acid (IA HA) is a well-known symptomatic treatment of knee osteoarthritis. The question arises whether a monoinjection (ie, single injection) could be as efficient as multi-injection (ie, 3–5 injections) regimens. Methods A meta-analysis of published studies relating to IA HA monoinjection trials was performed. The efficacy criterion was the Western Ontario and MacMaster Universities pain subscore. Any study design was accepted, from randomized control trials to single-arm observational open-label studies. An extensive search was performed using PubMed, Google, Google Scholar, and references found in recent meta-analyses, for all articles published before end of April 2018. Population profiles were analyzed in terms of age, sex, body mass index (BMI), and Kellgren-Lawrence (KL) radiology grades. Results of intra-articular single injection of placebo were collected to create a database allowing post hoc comparisons. Each IA HA study arm was compared to an IA placebo arm (either pooled or not), to present a similar KL profile controlled with the χ 2 test. The effect size (ES) (95% CI) and P values were calculated and synthesized for each follow-up visit at 1, 2, 3, and 6 months. In parallel, a global approach was used to represent the variations from baseline for each group or subgroup studied. Results From 1547 citations, 28 studies were included in the meta-analysis, representing 4129 patients treated with monoinjection: 3360 received IA HA and 769 patients received IA placebo. The mean (SD) IA HA patient was 61.2 (9.6) years, 63% women, BMI 28.0 (4.1), 47% KL III, and 3% KL IV. A good placebo KL profile matching was obtained for 26 of the 31 IA HA arms. For the whole IA HA population, ES = 0.30 (95% CI, 0.25–0.35) at 3 months and ES = 0.39 (95% CI, 0.33–0.44) at 6 months. In a restricted analysis, after removal of outliers, poorly KL matched and active arms <30 patients, results remained unchanged, ES = 0.29 (95% CI, 0.23–0.34) and ES = 0.40 (95% CI, 0.34–0.45) at 3 and 6 months respectively, whilst heterogeneity was improved. Conclusions There are certainly limits to the post hoc placebo comparison method, for individual studies. But for each synthesis per subgroup or group, the results were properly confirmed using multiple statistical approaches and weighing methods. This meta-analysis suggests that monoinjections produce results similar to multi-injections of IA HA in terms of pain relief in the treatment of knee osteoarthritis. ( Curr Ther Res Clin Exp . 2019; 80:XXX–XXX)

Cocktail of Hyaluronic Acid and Human Amniotic Mesenchymal Cells Effectively Repairs Cartilage Injuries in Sodium Iodoacetate-Induced Osteoarthritis Rats

“…It has been confirmed that the use of HA alone has obvious curative effects for the cartilage injury and has been widely used clinically (Sampson et al, 2013;Park et al, 2015). HA is commonly used in the treatment of cartilage damage in clinic as a second-generation HA joint cavity injection product (Vincent, 2019). However, there are also some reports showing its very limited efficacy (Rutjes et al, 2012;Jevsevar et al, 2015).…”

Specific concentration of hyaluronan amide derivative induces osteogenic mineralization of human mesenchymal stromal cells: Evidence of RUNX2 and COL1A1 genes modulation

“…The osteogenic differentiation of MSCs is a complex process influenced by ECM. HA represents one of the major components of ECM that has a physiological role in both healthy and OA joints (Bagga, Burkhardt, Sambrook, & March, 2006;Chernos et al, 2017;George, 1998;Moreland, 2003;Vincent, 2019;Yasuda, 2009). HA-derivatives are currently used clinically, since they have been shown to exert specific effects (i.e., anti-inflammatory, analgesic), and they are lubricant, able to restore joint viscosupplementation function of synovial fluid, shock absorber, and joint stabilizer (Bagga et al, 2006;Chernos et al, 2017;George, 1998;Yasuda, 2009).…”

Single-Dose Intra-Articular Administration of a Hybrid Cooperative Complex of Sodium Hyaluronate and Sodium Chondroitin in the Treatment of Symptomatic Hip Osteoarthritis: A Single-Arm, Open-Label, Pilot Study

“…The role of i.a. hyaluronic acid is well established in knee OA [20,[27][28][29][30][31], although its use Data are mean ± standard deviation (SD) * P \ 0.001 vs. baseline at all evaluated time points in hip OA is less well documented. Anatomical and biomechanical differences between the knee and hip joints mean that the rheological properties of hyaluronic acid products formulated for use in knee OA are not ideal for administration in hip OA.…”