In this independent prospective randomized trial, we compared the clinical effectiveness, functional outcome and patient satisfaction following intra articular injection with two viscosupplementation agents - Hylan G-F-20 (n=199) and Sodium Hyaluronate (n=193) in patients with osteoarthritis (OA) of the knee. All patients were prospectively reviewed by blinded independent assessors at pre injection, 6 weeks, 3, 6, 12 months. Knee pain and patient satisfaction were measured on a visual analogue scale. Functional outcome was assessed using WOMAC, Oxford knee score and EuroQol EQ-5D scores. Knee pain on VAS improved from 6.7 to 3.2 by 6 weeks (p=0.02) and was sustained until 12 months (3.7, p=0.04) with Hylan G-F 20. In the Sodium Hyaluronate group, pain improved from 6.6 to 5.7 at 6 weeks (p>0.05) and to 4.1 at 3 months (p=0.04) but was sustained only until 6 months (5.9, p>0.05). Improvement in the WOMAC pain subscale was significantly superior in the Hylan G-F 20 group at 3 months (p=0.02), 6 months (p=0.01) and 12 months (p=0.007). There was no significant difference in the EQ-5D scores at 6 weeks and 3 months between the two groups. The numbers of treatment related adverse events were higher (39 vs. 30) in the Hylan G-F 20 group. One patient in the Hylan G-F 20 group who had a serious adverse event was also included in the final analysis. Although both treatments offered significant pain reduction, it was achieved earlier and sustained for a longer period with Hylan G-F 20. From this study, it appeared that the clinical effectiveness and general patient satisfaction are better amongst patients who received Hylan G-F 20.
OBJECTIVE: To compare the efficacy and safety of intraarticular hylan and 2 hyaluronic acids (HAs) in osteoarthritis (OA) of the knee. METHODS: This was a multicenter, patient-blind, randomized controlled trial in 660 patients with symptomatic knee OA. Patients were randomly assigned to receive 1 cycle of 3 intraarticular injections per knee of 1 of 3 preparations: a high molecular weight cross-linked hylan, a non-cross-linked medium molecular weight HA of avian origin, or a non-cross-linked low molecular weight HA of bacterial origin. The primary outcome measure was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at 6 months. Secondary outcome measures included local adverse events (effusions or flares) in injected knees. During months 7-12, patients were offered a second cycle of viscosupplementation. RESULTS: Pain relief was similar in all 3 groups. The difference in changes between baseline and 6 months between hylan and the combined HAs was 0.1 on the WOMAC pain score (95% confidence interval [95% CI] -0.2, 0.3). No relevant differences were observed in any of the secondary efficacy outcomes, and stratified analyses provided no evidence for differences in effects across different patient groups. There was a trend toward more local adverse events in the hylan group than in the HA groups during the first cycle (difference 2.2% [95% CI -2.4, 6.7]), and this trend became more pronounced during the second cycle (difference 6.4% [95% CI 0.6, 12.2]). CONCLUSION: We found no evidence for a difference in efficacy between hylan and HAs. In view of its higher costs and potential for more local adverse events, we see no rationale for the continued use of hylan in patients with knee OA.
Viscosupplementation consists of injecting exagenous hyaluronan (HA) into the synovial joints to restore the normal rheological environment which deteriorates severely in osteoarthritic (OA) joints. Efficacy might be related to the rheological properties and molecular weight (MW) of the hyaluronan preparations. This prospective, controlled, double-blind, randomised clinical trial was aimed at comparing the elastoviscous properties of a high molecular weight viscosupplement, hylan G-F 20, with that of a lower molecular weight hyaluronan product in order to determine the relationship of elastoviscosity to efficacy, alongside placebo, in the treatment of patients with knee OA. The results were analysed as a "completers" analysis with 59 patients. Primary outcome measures included the Western Ontario and Mc Master Universities' Osteoarthritis Index (WOMAC) for pain, stiffness and function scores, and patient and physician global assessments (0-100 scale). For patient (PGA) and physician global assessments (PhGA), the 0-100 scale was used, with 100 being the worst. Follow-up assessments were made at intervals of 1, 3 and 6 months after the first injection. Local adverse events, such as transient pain at the injection site or warm knee lasting for one night, were recorded in two patients (3%). In all groups, the WOMAC pain score exhibited a significant difference from the baseline value; neither treatment group was significantly different from the placebo group, but total pain score was significantly better than baseline for both of the HA groups at the end of 6 months (p < 0.05). Improvement in WOMAC physical function score favoured both sodium hyaluronate and hylan G-F 20 after the first month, and remained significant until the end of 6 months (p < 0.01). In the placebo group, the physical function scores became worse after the end of the 1st month; the scores at the end of 6 months were no different from those at the beginning. The WOMAC stiffness scores of both of the hyaluronic acid groups improved with the first injection, and remained significantly better than the placebo group until the end of the survey (p < 0.001). All groups expressed improvement with PGA scores after the first injection. At the end of 6 months all three groups were similar, but the treatment groups were significantly better than the placebo group (p < 0.05), and all were significantly better than at the beginning (p < 0.05). The PhGA scores were similar in all groups until after the third injection. The second group was slightly better in the controls at 1 and 3 months, but all the groups were similar at the end of 6 months. Although the placebo group seemed worse, it was not statistically significant. Compared with lower molecular weight HA, the higher molecular weight HA might be more efficacious in treating knee OA, but heterogeneity of previous studies limited definitive conclusions. Patients treated by injection of either of two hyaluronan preparations showed clinical improvement for pain, though no different from the placebo group; WOMAC stiffness scores were better than placebo in the HA groups, whereas PGA scores showed improvement in all groups but HA groups were better than placebo. PhGA scores were worse in the placebo group, but not to a statistically-significant extent. The HA groups did not differ in terms of clinical efficacy.
OBJECTIVES: To compare the long-term effects of high and low molecular weight hyaluronic acid (HA) applications in severe (Kellgren Lawrence stage III) osteoarthritis (OA) of the knee. METHODS: In a prospective clinical trial 184 knees (92 patients) with radiographic Kellgren Lawrence stage III OA were randomized to receive either 3 intra-articular high molecular weight HA (Hylan G-F 20) injections or 3 low molecular weight HA (Orthovisc) injections at one-week intervals. Patients were evaluated by the Hospital for Special Surgery (HSS) Knee Score and were followed-up for 12 months. RESULTS: The total HSS score in high molecular weight HA patients improved from 71.8+/-11.6 to 86.7+/-11.6 and in low molecular weight HA patients from 66.7+/-11.0 to 86.6+/-9.1 at the end of the trial (p < 0.01). There were no statistically significant differences between the groups and both had improved in all parameters at the latest follow-up (p = 0.000). CONCLUSIONS: Three intra-articular injections at intervals of 1 week of both HA preparations resulted in a pronounced reduction in pain and improved function as measured by the HSS score during a period of 52 weeks, without complications.
A pilot study was designed to investigate the efficacy of two different hyaluronic acid preparations combined to physical therapy in patients with knee osteoarthritis in terms of reduction in pain and disability and muscle strengthening. Thirty-seven patients with symptomatic osteoarthritis of the knees were randomly assigned into three groups. First group received a lower molecular weight hyaluronic acid plus physical therapy, second group received a higher molecular weight hyaluronic acid plus physical therapy, and the third group received physical therapy alone. The isokinetic knee muscle strengths and index of severity for osteoarthritis of the knee scores were evaluated at baseline, at the end of treatment (3 weeks) and at 3 months of follow up. At both short-term (3 weeks) and long-term (3 months) evaluations, index of severity for osteoarthritis of the knee scores were reduced in all three groups, while there was no significant muscle strengthening.
In this independent prospective randomized trial, we compared the clinical effectiveness, functional outcome and patient satisfaction following intra articular injection with two viscosupplementation agents - Hylan G-F-20 (n=199) and Sodium Hyaluronate (n=193) in patients with osteoarthritis (OA) of the knee. All patients were prospectively reviewed by blinded independent assessors at pre injection, 6 weeks, 3, 6, 12 months. Knee pain and patient satisfaction were measured on a visual analogue scale. Functional outcome was assessed using WOMAC, Oxford knee score and EuroQol EQ-5D scores. Knee pain on VAS improved from 6.7 to 3.2 by 6 weeks (p=0.02) and was sustained until 12 months (3.7, p=0.04) with Hylan G-F 20. In the Sodium Hyaluronate group, pain improved from 6.6 to 5.7 at 6 weeks (p>0.05) and to 4.1 at 3 months (p=0.04) but was sustained only until 6 months (5.9, p>0.05). Improvement in the WOMAC pain subscale was significantly superior in the Hylan G-F 20 group at 3 months (p=0.02), 6 months (p=0.01) and 12 months (p=0.007). There was no significant difference in the EQ-5D scores at 6 weeks and 3 months between the two groups. The numbers of treatment related adverse events were higher (39 vs. 30) in the Hylan G-F 20 group. One patient in the Hylan G-F 20 group who had a serious adverse event was also included in the final analysis. Although both treatments offered significant pain reduction, it was achieved earlier and sustained for a longer period with Hylan G-F 20. From this study, it appeared that the clinical effectiveness and general patient satisfaction are better amongst patients who received Hylan G-F 20.
