DUROLANE: The Science of the Single Injection

Transcription

1 : The Science of the Single Injection is a stabilised, hyaluronic acid (HA)-based, viscoelastic gel for the intra-articular treatment of mild to moderate osteoarthritis of the knee and hip. is different from all other HA products. uses patented NASHA TM technology which gives it a unique gel particle structure. is resistant to dilution and degradation, 1,2 giving a longer residence time in the synovial joint compared to other HA products. 3-5 Stabilised HA: 1% stabilisation forms a flexible molecular network which resists physiological catabolism 1,2 Stabilisation 1. Mendoza G et al. Degradation of hyaluronan by an oxidative system comprising cupric ions and hydrogen peroxide. Free Radical Research 27; 41: S Edsman K et al. The ability of Durolane to withstand degradation by free radicals. Poster presented at the 55th Annual Meeting of the Orthopaedic Research Society, February 22-25, 29; Las Vegas, Nevada, USA. 3. Lindqvist U et al. Elimination of stabilised hyaluronan from the knee joint in healthy men. Clin Pharmacokinet 22; 41: Larsen NE et al. Clearance kinetics of a single injection crosslinked hylan-based viscosupplement in a rabbit model. Osteoarth Cart 27; 15(Suppl. C): C Brown TJ et al. Turnover of hyaluronan in synovial joints: elimination of labelled hyaluronan from the knee joint of the rabbit. Exp Physiol 1991; 76:

2 Resistance to degradation Edsman K et al. The ability of Durolane to withstand degradation by free radicals. Poster presented at the 55th Annual Meeting of the Orthopaedic Research Society, February 22-25, 29; Las Vegas, Nevada, USA. 2 To compare the susceptibility of and Hylan G-F 2 to free radical attack in an in-vitro model. showed stable storage modulus during degradation with free radicals. The viscoelastic properties of Hylan G-F 2 decreased rapidly when exposed to free radicals both in diluted and undiluted conditions. Residence time Studies Lindqvist U et al. Elimination of stabilised hyaluronan from the knee joint in healthy men. Clin Pharmacokinet 22; 41: Larsen NE et al. Clearance kinetics of a single injection crosslinked hylan-based viscosupplement in a rabbit model. Osteoarth Cart 27; 15(Suppl. C): C64. 4 Brown TJ et al. Turnover of hyaluronan in synovial joints: elimination of labelled hyaluronan from the knee joint of the rabbit. Exp Physiol 1991; 76: Hyaluronic acid (mg) 3 Resistance to degradation/residence time 7 Hylan G-F 2 4 A B 6 1KDa HA 5 Storage modules G (PA) 1 Storage modules G (PA) Time Time diluted Hylan G-F 2 Hylan G-F 2 diluted 2 mg/ml HA solution Normal Synovial fluid OA Synovial fluid Time (weeks) Storage modulus at 1Hz during degradation by hydroxyl radicals. A) and 2mg/ml HA solution. B) and Hylan G-F 2 diluted and undiluted. has a greater ability to retain its viscoelastic properties when exposed to free radicals. The enhanced viscoelastic properties of during degradation may be due to the network of crosslinked HA obtained by the NASHA technology. The data support the use of to obtain a satisfactory intra-articular effect and residence time. Comparison of the elimination of hyaluronic acid from the joint space of humans and rabbits as a function of time for and for products containing non-stabilised hyaluronic acid. Conclusion The higher HA concentration of linked with its enhanced abilities to resist degradation provides much greater residence time in the joint compared with other HA products.

3 Safety Safety Ottaviani RA et al. Inflammatory and immunological responses to hyaluronan preparations. J Bone Joint Surg 27; 89: To test the local inflammatory and immunological effects of three different hyaluronanderived products (Hylan G-F 2, LMW HA and Supartz) using a mouse pouch model. All three products led to a significant increase in total membrane cellularity due to inflammatory cell influx. Increased lymphocyte counts were seen in membranes stimulated by Hylan G-F 2. Injection of Hylan G-F 2 also led to an antibody response against a non-hyaluronan portion of the product. Optical density Antibody binding to Hylan G-F 2 and HA Injection group Hylan G-F 2 HA PBS UHMWPE Hylan G-F 2 LMW HA Supartz All three HA products studied caused an inflammatory soft-tissue reaction. Only the non-hyaluronan portion of Hylan G-F 2 created an immunological response. This component of Hylan G-F 2 may be the target of adverse responses in patients. Wooley PH et al. Evaluation of the biocompatibility of Durolane using the murine air pouch model. Poster presented at the 55th Annual Meeting of the Orthopaedic Research Society, February 22-25, 29; Las Vegas, Nevada, USA. 7 To investigate the potential antigenicity of using a mouse air pouch model. A significant increase in pouch thickness was measured in the Hylan G-F 2 group but not in the group. Hylan G-F 2 showed the highest level of responsiveness and cellular infiltration, with a significant increase in both inflammatory and fibroblastic cells. Antibody binding to and Hylan G-F 2 showed low levels of binding activity, with the exception of pouch mice injected with Hylan G-F 2 binding to Hylan G-F 2, which was consistently elevated. Optical density 45 unit Adapted from Wooley PH et al, 29. Hylan G-F 2 Antibody binding to viscosupplements PBS Hylan G-F 2 The findings suggest that is not antigenic to an excessive level in this murine model. Little antibody reactivity or lymphocyte response were observed in the group. is less biologically stimulatory than Hylan G-F 2. Safety

4 Pain relief Pain relief Böttger M et al. provides anti-nociceptive effects in a model of articular joint pain. Poster presented at the 28 World Congress on Osteoarthritis, September 18-21, Rome, Italy. 8 To compare the anti-nociceptive effects of with 75kDa HA in an in vivo animal model of induced joint pain. A single injection of on Day 1 showed similar effects on pain to morphine on each testing day until the end of the study. provided significant anti-nociceptive effects compared to the saline control both in terms of force required to initiate a pain response and static motor behaviour at Days 1, 2, 4, 14 and kDa HA, in contrast, did not provide as good protection from pain when compared to. From Day 4 until the end measurement, the 75kDa HA behaved similarly to a single injection of saline. Incapacitance testing revealed significant differences that were seen at Days 1, 2 and 14 between the saline and groups. 75kDa HA-treated animals had a similar response to those treated with saline. A single intra-articular injection of provides anti-nociceptive effects until at least Day 28. The findings suggest that modifications in the NASHA gel provide superior pain relief compared to 75kDa HA in this model. mitigates incapacitance during weight bearing Mechanical Threshold (g) kDa HA Saline Pre-treatment value = 247.5g Base Day 1 Day 2 Day 4 Day 7 Day 14 Day 21 Day 28 Mechanical threshold data (means ± SEM) for the affected limb. The mean force required to cause withdrawal for the morphine group was 246.3g. Base = Baseline testing. Arrow indicates when the injections of, 75kDa HA and saline were performed. Weight on affected limb (%) kDa HA Equal distribution of load 35 Base Day 1 Day 2 Day 4 Day 7 Day 14 Day 21 Day 28 Incapacitance data for the affected limb. Data are represented as means ± SEM. The percentage weight loaded on the affected limb for saline was 45.2% and morphine was 5.1%. Base = Baseline testing. The arrow indicates when the injections of and 75kDa HA were performed. Pain relief

5 Scientific documentation 1. Mendoza G et al. Degradation of hyaluronan by an oxidative system comprising cupric ions and hydrogen peroxide. Free Radical Research 27; 41: S Edsman K et al. The ability of Durolane to withstand degradation by free radicals. Poster presented at the 55th Annual Meeting of the Orthopaedic Research Society, February 22-25, 29; Las Vegas, Nevada, USA. 3. Lindqvist U et al. Elimination of stabilised hyaluronan from the knee joint in healthy men. Clin Pharmacokinet 22; 41: Larsen NE et al. Clearance kinetics of a single injection crosslinked hylan-based viscosupplement in a rabbit model. Osteoarth Cart 27; 15(Suppl. C): C Brown TJ et al. Turnover of hyaluronan in synovial joints: elimination of labelled hyaluronan from the knee joint of the rabbit. Exp Physiol 1991; 76: Ottaviani RA et al. Inflammatory and immunological responses to hyaluronan preparations. J Bone Joint Surg 27; 89: Wooley PH et al. Evaluation of the biocompatibility of Durolane using the murine air pouch model. Poster presented at the 55th Annual Meeting of the Orthopaedic Research Society, February 22-25, 29; Las Vegas, Nevada, USA. 8. Böttger M et al. provides anti-nociceptive effects in a model of articular joint pain. Poster presented at the 28 World Congress on Osteoarthritis, September 18-21, Rome, Italy. Abbreviations HA Hyaluronic Acid NASHA Non-Animal Stabilised Hyaluronic Acid OA Osteoarthritis LMW Low Molecular Weight kda Kilodaltons