Clinical effectiveness and safety of intra-articular injection of HYALGO in the management of knee osteoarthritis symptoms: A multicenter prospective study

Abstract

Background: The reduced concentration of hyaluronic acid in the synovial fluid, leading to impairment of joint function and painful symptomatology during knee osteoarthritis (OA), can be restored by using injectable formulations of hyaluronic acid (HA) and chondroitin sulfate (CS), variable for relative composition, HA/CS molecular modifications, and injection protocols. The present study aims to assess the safety and performance of the intra-articular (IA) viscosupplementing agent HYALGO, a formulation combining 40 mg/mL HA (>1700 kDa) and 40 mg/mL CS, in the treatment of patients suffering from knee OA. Methods: 74 patients affected by knee lesions classified as grade II and III according to Kellgren and Lawrence classification were prospectively recruited and treated with three HYALGO injections (2 mL) given one week apart. Visual analogue scale (VAS) pain changes were monitored at each injection and over-time at 6, 14, and 26 weeks of follow-up. Secondary endpoints were: Western Ontario McMaster University Osteoarthritis index (WOMAC), Patient's Global Assessment (PGA) score, Clinical Observer Global Assessment (COGA) score, Outcome Measures in Rheumatology Committee (OMERACT) and Osteoarthritis Research Society International (OARSI) responders rates. Patients were also assessed for changes in their ultrasound joint scores according to the criteria of the OMERACT US Task Force Group. Results: Pain reduction was statistically significant starting from the first IA injection. Mean pain reduction from baseline to week 26 was À90.6%. At 26 weeks, WOMAC Pain was reduced by À62.7%, WOMAC Stiffness by À47.2%, WOMAC Physical Function by À54.1%; Total WOMAC by À53.8%. The VAS PGA change from baseline was À48.0 [mm] and VAS COGA -41.0 [mm]. Responders at week 26 were 78.4%. Ultrasound parameters (joint effusion, synovial thickness, and popliteal cysts) improved or remained stable from baseline to week 6. Conclusions: Three injections of HYALGO were safe and effective to manage symptomatic knee OA, with a beneficial effect that increased progressively over time, peaking 6 months after injection.

Hyaluronic Acid-Based Injective Medical Devices: In Vitro Characterization of Novel Formulations Containing Biofermentative Unsulfated Chondroitin or Extractive Sulfated One with Cyclodextrins

“…To date, almost all the CS used either as food ingredients or as pharma-active molecules and as macromolecules in solution/combination with HA are of animal extractive origin [20,21,[27][28][29]. In this respect, as previously discussed, the commercialized CS are very heterogeneous molecules.…”

“…The authors reported that the proposed intervention was able to assure pain relief and improved function over 6 months of follow-up [28]. Interestingly, the combined intra-articular injection of HA and CS was effective since the first application, probably due to an anti-inflammatory effect [29]. More interesting, a novel biofermentative unsulfated chondroitin has been obtained at a high purity grade by biotechnological inventive processes and reported a molecular weight like those of fish (shark fins) extractive chondroitin sulfate, this one being the larger molecules among extractive CS.…”

Engineering of Viscosupplement Biomaterials for Treatment of Osteoarthritis: A Comprehensive Review

“…This study concluded that three injections of HYALGO were safe and effective to manage symptomatic knee OA, with a beneficial effect that increased progressively over time, peaking 6 months after injection. [ 69 ] The histological changes in knee cartilage and bone following the administration of two different CS products in two experimental OA models (MIA) in rats were studied ( Figure ). It was found that high‐quality pharmaceutical‐grade CS ensures optimal efficacy and safety of the final product in patients with OA.…”