Delayed Total Knee Replacement with Hylan G-F 20.

We retrospectively examined prospective data on the incidence and time to total knee replacement (TKR) in (1) patients with grade IV osteoarthritis (OA) treated with hylan G-F 20 from 1997 to 2010 (full cohort; 1,863 knees) and (2) a patient subset treated from 1997 to 2003 (original cohort; 1,187 knees) to determine any continued hylan G-F 20 influence on TKR delay. In both the cohorts, 25 to 28% knees underwent a TKR, with an average of 2.8 to 3.1 years occurring between hylan G-F 20 and surgery. Age was a significant predictor of time to TKR. Knee synovitis increased slightly with repeat courses; most cases considered mild or moderate. Survival analysis showed that TKR was delayed for > 7 years in 75% of 1,863 grade IV OA knees (1,342 patients) treated with hylan G-F 20 in an orthopedic practice. Consistent with our previous report (Waddell and Bricker, 2007), we show hylan G-F 20 continues to delay the need for TKR.

Comparison of Efficacy and Tolerability of Hylan G-F 20 in Patients with and without Effusions at the Time of Initial Injection.

An effusion at the onset of viscosupplementation has been thought to diminish the efficacy and increase adverse event rates. This study compares efficacy of hylan G-F 20 in patients with and without an effusion. Patients with knee osteoarthritis (OA) received three weekly injections of hylan G-F 20. A total of 50 patients with an effusion requiring aspiration were compared with 50 matched patients without an effusion. Outcome measurements included Western Ontario and McMaster's Universities Osteoarthritis index (WOMAC) and visual analog scale (VAS). Patients were followed for 26 weeks. Both effusion and control group VAS was significantly lowered at all time points. WOMAC scores improved (p < 0.025) at all visits in the effusion group except for WOMAC A-1 week 14. Control WOMAC scores also significantly improved at all visits (p < 0.027), except for full WOMAC and WOMAC A-1 at week 1. Neither group experienced an adverse event. Presence of an effusion at onset of viscosupplementation requiring aspiration does not negatively impact efficacy of hylan G-F 20 or increase adverse event rates.

No conclusive evidence that histologically found granulomas and acute local reactions following hylan G-F 20 injections are related or have clinical significance.

Osteoarthritic (OA) knee pain can be successfully treated with hylan G-F 20 (Synvisc, Sanofi Biosurgery, Cambridge, MA) with few local adverse events. However, a few studies have identified hyaluronate positive (HA+) granulomas in the synovial tissue of patients treated with hylan G-F 20 raising the question of their relationship and clinical significance. To understand the potential relationship of HA+ granulomas with the occurrence of acute local reactions (ALRs), we evaluated the synovial tissue of OA patients undergoing total knee replacement that had previously been treated with hylan G-F 20 (n = 101) or had not been treated (n = 20). Granulomas were observed in nine patients, of which eight were in the hylan G-F 20 group (7.9%); HA+ granulomas were identified in six of these eight patients (5.9%). Three of the six patients with HA+ granulomas experienced an ALR within 30 days of administering an injection. Overall, we found no consistent relationship between histologically found HA+ granulomas and the occurrence of an ALR following hylan G-F 20 treatment. These microscopic granulomas were not associated with any symptoms and likely have little clinical significance. The low occurrence of granulomas and/or ALRs should not preclude use of hylan G-F 20 for the treatment of knee pain associated with OA.

The use of hyaluronan after arthroscopic surgery of the knee.

Viscosupplementation is defined as the use of intra-articular hyaluronan therapy for symptomatic osteoarthritis (OA). Originally used for the treatment of ophthalmic disorders, viscosupplementation has been available for over a decade in the United States for the treatment of pain secondary to OA of the knee in patients who have not responded adequately to conservative oral pharmaceuticals including nonsteroidal anti-inflammatories and simple analgesics. The majority of patients with symptomatic knee OA will have evidence of meniscal and/or articular surface pathology, and most orthopaedic surgeons include arthroscopic surgery as a possible treatment modality for the symptomatic patient. Although arthroscopic meniscectomy is the most commonly performed orthopaedic procedure in the United States, in patients with concomitant OA, disease-related pain can persist after arthroscopic surgery. This article reviews some of the more recent evidence recommending the use of viscosupplementation for the management of symptomatic knee OA and pain relief after arthroscopy.

Viscosupplementation with hylan g-f 20 in patients with osteoarthrosis of the knee.

Viscosupplementation (VIS) is one of several treatment modalities for osteoarthritis of the knee. It is useful in the treatment of osteoarthritis when other methods of conservative care have failed and it may be a safer method of treatment than oral chemical therapy which can have significant side effects with even short-term usage. The biochemical effects of hyaluronic acid are incompletely understood, however there are several accepted modes of action which result in a positive clinical effect on the function of the knee joint. There is some evidence that hyaluronic acid preparations with a higher molecular weight may be more beneficial to the patient. It is commonly used after arthroscopic meniscectomy and or debridement of the knee in a patient with chondral disease. The clinical effects have been well documented in multiple studies in patients with mild to moderate osteoarthritis in study groups before or after arthroscopic surgery of the knee. Adverse events do occur and are easily treated with only rare case reports of systemic effects. Furthermore, there is some evidence that VIS can prolong the need for total knee arthroplasty in the older patient as well.

Chronic knee effusions in patients with advanced osteoarthritis: implications for functional outcome of viscosupplementation.

Intra-articular injection of exogenous hyaluronan (viscosupplementation) is an effective treatment for knee pain due to osteoarthritis, but the amount of dilution of the viscosupplement by the synovial fluid, which could affect efficacy, has not been previously considered. In this study, the synovial fluid volume was measured in patients with advanced osteoarthritis and the variation in viscosupplement concentration that would have occurred had the patients received that treatment was calculated. A closed aspiration was performed under anesthesia in this consecutive, prospective series of patients undergoing total joint arthroplasty for advanced osteoarthritis. Any remaining synovial fluid was collected by means of open aspiration following an arthrotomy. Overall, 27.0 +/- 15.5 mL (range: 10-70 mL) of synovial fluid was present in the joints. Irrespective of the particular proprietary hyaluronan product, the viscosupplement concentration would have varied by an approximate factor of 6. Interpatient variation in volume of synovial fluid may explain some of the observed variations in efficacy in patients treated with viscosupplementation. Stricter attention to the possibility of a joint effusion and aspiration of the joint where indicated might lead to improved results.

Clinical experience with the effectiveness and tolerability of hylan G-F 20 in 1047 patients with osteoarthritis of the knee.

This retrospective review evaluates the effectiveness and tolerability of hylan G-F 20 for relief of pain due to knee osteoarthritis in a large orthopedic practice over a 5-year period. Prospectively collected data from patients who initiated intra-articular hylan G-F 20 (3 weekly injections) for osteoarthritis knee pain treatment were analyzed. Efficacy variables included physician visual analogue scale (VAS: 100 mm), and patient rating of pain, mobility, and amount of pain medication taken after treatment. Patients (n=1047; 1489 knees) were an average age of 65.3 years, 60% female, and 71% had radiologic osteoarthritis grade IV. Mean VAS scores significantly improved with hylan G-F 20 compared to baseline at all time points (P<.0001). Most knees (62%-89%) responded positively with hylan G-F 20. Pain and mobility improved and less pain medication was needed after therapy. The incidences of local adverse events were 5.2% per patient and 1.2% per injection; most local adverse events were mild or moderate, with severe local events in 0.3% of injections. Our clinical experience shows that hylan G-F 20 effectively relieves osteoarthritis knee pain (as indicated) and reduces pain medication needed for up to 6 months with a low incidence of local adverse events.

A second course of hylan G-F 20 for the treatment of osteoarthritic knee pain: 12-month patient follow-up.

This prospective open-label study evaluated the efficacy and tolerability of a second course of hylan G-F 20 for the treatment of osteoarthritic knee pain over a 12-month period in patients who previously experienced a beneficial initial course of therapy. Men or women aged > or = 40 years with knee osteoarthritis received 3 weekly injections of hylan G-F 20. Consecutive patients requesting a second course of therapy were enrolled from October 2000 to January 2001. The mean time between the first and second courses of hylan G-F 20 was 19.6 months. All efficacy parameters significantly improved (P<.001) from baseline at weeks 1, 2, 4, 8, 12, 26, and 52. Improvements from baseline to weeks 26 and 52 for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) index question A1, WOMAC domain C, and total WOMAC were 1.39+/-0.11 and 1.1+/-0.12, 18.50+/-1.43 and 13.69+/-1.54, and 26.77+/-1.97 and 19.8+/-2.13, respectively. Significant improvements from baseline were maintained for patient and physician VAS to week 26 (patient: 48.66+/-2.52; investigator: 51.51+/-2.34) and week 52 (patient: 46.10+/-2.73; investigator: 47.23+/-2.52). A second course of hylan G-F 20 therapy was generally well-tolerated; the types of local events observed in this study were not qualitatively different from those in the current product information and published literature. For continued relief of osteoarthritic knee pain, this study supports repeat use of hylan G-F 20 in patients who had a previous successful course of therapy.

Increased intercellular communication through gap junctions may contribute to progression of osteoarthritis.

Our aim was to support the hypothesis of a specific association between gap junctions in synovial tissue and the presence of osteoarthritis, as evidenced by differences between osteoarthritis and non-osteoarthritis synovia in the number of gap junctions, the amount of gap-junction protein, and the amount of enzymatic activity produced through a pathway mediated by gap-junction intercellular communication. An average of 4.41 gap junctions were found per 100 cells counted in the osteoarthritis synovia, compared with 1.00 in the controls. The amount of the gap-junction protein connexin 43 in synovial lining cells was approximately 50% greater in patients with osteoarthritis. Synovial lining cells from patients with osteoarthritis produced matrix metalloproteinases constitutively and, at higher levels, in response to stimulation by interleukin-1 beta. In both cases, intercellular communication through gap junctions was shown to be critical to the ability of the cells to secrete matrix metalloproteinases. Overall, the results indicated that gap junctions between synovial lining cells were altered significantly in patients with osteoarthritis, as a consequence of the disease process or as part of the causal chain. In either case, gap junctions seem to be a rational therapeutic target.