Safety and performance of Hydros and Hydros-TA for knee osteoarthritis: a prospective, multicenter, randomized, double-blind feasibility trial

Abstract

BackgroundStudies have evaluated the concomitant use of hyaluronan (HA) with steroids, anti-inflammatory drugs and analgesic agents in an attempt to magnify the extent and duration of pain relief due to knee osteoarthritis. To date there has not been an intra-articular combination therapy available for relief of knee osteoarthritis symptoms – one that combines the fast acting onset of symptom relief provided by a corticosteroid with the long-lasting symptom relief provided by HA in a single injection. The objective of this study was to evaluate the safety and preliminary performance of two new HA formulations, Hydros (hyaluronan-based hydrogel suspended in hyaluronan solution) and Hydros-TA (HA plus 10 mg of triamcinolone acetonide [TA]) in subjects with knee osteoarthritis.MethodsWe conducted a Phase 2 prospective, multicenter, randomized, double-blind feasibility trial. Participants (n = 98; mean age 60 years) with knee osteoarthritis (Kellgren-Lawrence grade 2 or 3) were randomized to three treatment groups: Hydros, Hydros-TA, and Synvisc-One® (hylan G-F 20). Participants received one 6 ml intra-articular injection in the treatment knee and were evaluated at 2, 6, 13, and 26 weeks post-treatment. Safety was assessed from adverse events at all study visits. The primary efficacy outcome was the change from baseline on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A (Pain) score for the treatment knee.ResultsAdverse events were similar across treatment groups with the most common being arthralgia, joint swelling, back pain, and joint stiffness. Arthralgia was reported 5 times with Synvisc-One, 4 with Hydros, and 1 with Hydros-TA. Each group demonstrated a reduction in the WOMAC A (Pain) score over 26 weeks: [least-square mean (standard error)] 30.5 (5.1) mm for Hydros; 34.4 (4.7) mm for Hydros-TA; 28.0 (5.4) mm for Synvisc-One and an observed improvement of 2.5 mm (p = 0.64) and 6.4 mm (p = 0.24) over Synvisc-One for Hydros and Hydros-TA, respectively.ConclusionsA single injection of Hydros or Hydros-TA was well-tolerated and relieved pain associated with knee osteoarthritis over 26 weeks. Data indicate that Hydros-TA had a more rapid pain relief compared to Hydros alone. A Phase 3 trial is underway to confirm these preliminary results.Trial registration numberNCT01134406.

Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco‐supplementation in Orthobiologics

“…[391] A systematic review, which included data from six randomized controlled trials comparing the effectiveness of PRP with other intra-articular injections, exercise, or analgesia for a minimum of 6 months PRP produced statistically significant improvements in WOMAC scores for up to 12 months. [393][394][395] www.advancedsciencenews.com www.advtherap.com HA hydrogel n/a Dexamethasone Cortocosteroid [310] Adant (Suprahyal) 500-1000 Tenoxicam NSAID [311] Variofill (Adoderm, Langenfeld, Gmbh) HMWCR Diclofenac Sodium clodronate Triamcinolone acetonide Ropivacaine HCl NSAID DMOAD Cortocosteroid Anaesthetic [312] [ 313] Hydros, Hydros-TA HMW Triamcinolone acetonide Cortocosteroid [314] Cingal 1900 Triamcinolone acetonide Cortocosteroid [315] Hylan GF-20 HMWCR Triamcinolone acetonide Cortocosteroid [316] HA solution 800 Mannitol Anti-oxidant [317] Go-on matrix Ostenil Plus 1500 Mannitol Anti-oxidant [320] Happyvix 1500 Mannitol Anti-oxidant [320] Happycross 1500 Mannitol Anti-oxidant [320] Synolis V-A 2000 Sorbitol Anti-oxidant [320] HA 4AR conjugate 2200 4 aminoresorcinol Anti-oxidant [321] Ostenil 1000-2000 l-glutathione Anti-oxidant [322] Arthrum HCS 2800 CS GAG [320] Surgical Syonium 2800 CS GAG [320] HA-sCT conjugate 200 Salmon calcitonin DMOAD [323] HA ADAMTS inhibitor n/a ADAMTS inhibitor DMOAD [324] HA hydrogel 60-120 Doxycycline DMOAD [296] Hanox Hanox M-XL 1500 n/a Cortivazol Triamcinolone hexacetonide Mannitol + lidocaine clorhydrate Cortocosteroid Cortocosteroid Anti-oxidant + local anaesthetic [325] n/a, not available; HMW, high molecular weight; HMWCR, high molecular weight cross-linked. [393][394][395] www.advancedsciencenews.com www.advtherap.com HA hydrogel n/a Dexamethasone Cortocosteroid [310] Adant (Suprahyal) 500-1000 Tenoxicam NSAID [311] Variofill (Adoderm, Langenfeld, Gmbh) HMWCR Diclofenac Sodium clodronate Triamcinolone acetonide Ropivacaine HCl NSAID DMOAD Cortocosteroid Anaesthetic …”

I.S.Mu.L.T. Hyaluronic acid injections in musculoskeletal disorders guidelines

“…Several studies investigated combined therapy with corticosteroids in various pathologies, as knee osteoarthritis, stenosing tenosynovitis of fingers flexor tendons, internal derangement of temporomandibular joint, adhesive capsulitis and lateral epicondylitis (Tab. XII) 89,148,[153][154][155][156][157] . Despite the different indications and protocols, all these studies suggested the superiority of the therapeutic association in terms of efficacy (pain reduction) compared to the use of each treatment alone.…”

“…Fifty-seven studies (40 RCTs and 17 systematic reviews) were selected 65,78,98,99,101,102,104,107,108,114,136,139,140,148,156,158,159, . Absolute contraindications are represented by hypersensitivity to products, suspect or presence of infections at injection skin site or selected joint, joint inflammatory states.…”

Severe Acute Localized Reactions Following Intra-Articular Hyaluronic Acid Injections in Knee Osteoarthritis

“…The role of intra-articular CS in the development of the acute reactions is somewhat unclear. While CS and HA injections may be used concomitantly to improve the overall functional response [24][25][26] or used 1 week apart to reduce the risk of pseudoseptic arthritis, 22 acute reactions have also been reported following intra-articular CS use. 17 Intra-articular CS injections given before or with HA have been suggested to promote infections.…”