OBJECTIVE: Hyaluronic acid (HA) polymers have been found to be useful as viscosupplements for the treatment of osteoarthritis (OA) in a number of clinical studies. It appears that HA with high molecular weights (HMW) are more effective than low molecular weight HA polymers. METHODS: A single blind, initial randomized study was conducted involving two randomly selected patient groups, which received injections of either placebo or BioHy, a highly purified HMW HA produced by bacterial fermentation. HA was administered intra-articularly and several functional tests, including pain level, stiffness, and physical function, were used to score efficacy at various intervals throughout the study. RESULTS AND CONCLUSION: The results through week 20 indicate that BioHy provides relief for osteoarthritic patients without causing adverse effects, although the study was not sufficiently powered to obtain statistically significant differences between the treatment groups.
A prospective, multicenter, randomized, double-blind, controlled trial was conducted in 226 patients with knee osteoarthritis to evaluate the safety and efficacy of intraarticular injections of sodium hyaluronate. Patients were randomized to three weekly injections of 30 mg sodium hyaluronate or physiologic saline (control) and were observed for an additional 25 weeks. In comparison with the control group, among patients who completed at least 15 weeks of the study and whose Western Ontario and McMaster Universities Osteoarthritis Index pain score for the contralateral knee was less than 12 at baseline, sodium hyaluronate injection resulted in improvement in Western Ontario and McMaster Universities Osteoarthritis Index pain score, patient and investigator global assessments, and pain on standing from Weeks 7 to 27. Fifty-eight percent of patients treated with sodium hyaluronate achieved a 5-unit or greater improvement in mean pain score from Weeks 7 through 27, compared with 40% of control patients. In addition, nearly twice as many patients treated with sodium hyaluronate as with saline (30% versus 17%, respectively) achieved a net improvement of at least 7 units. In contrast to treatment with saline, Western Ontario and McMaster Universities Osteoarthritis Index pain score for the contralateral knee was inversely related to the magnitude of improvement after treatment with sodium hyaluronate. Few side effects were attributed to treatment, and no differences between treatment groups were seen in this respect (sodium hyaluronate, nine [8%]; saline, 11 [10%]). The incidence of injection site reactions was low (sodium hyaluronate, 1.2 %; saline, 1.5%). The results indicate that sodium hyaluronate treatment is well tolerated and produces statistically and clinically significant improvement of symptoms in patients with mild to moderate knee osteoarthritis in whom pain in the contralateral knee is relatively modest.
OBJECTIVE: To determine efficacy and safety of intraarticular (IA) hyaluronic acid (HA; Hyalgan) versus placebo and a nonsteroidal antiinflammatory drug for osteoarthritis (OA) of the knee. METHOD: A series of 5 weekly IA injections of HA (20 mg each) was compared to placebo or oral naproxen in a 26 week, double blind, masked observer, multicenter trial of 495 patients with idiopathic OA. Acetaminophen was permitted for escape analgesia. The primary measurement was pain experienced on a 50 foot walk test for those completing the study (completers) as measured on a 10 cm visual analog scale (VAS). Also measured were the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index (pain, stiffness, function) and categorical assessments of pain. RESULTS: Patients receiving HA improved more with respect to pain on the 50 foot walk compared to placebo at Week 26 (HA vs placebo difference 8.8 mm; p < 0.005); 56% of HA treated patients compared to 41 % of placebo treated patients had > or = 20 mm reduction in the VAS from Week 5 continuously through Week 26 (p=0.031). At 26 weeks, more HA treated patients (47.6%) had slight pain or were pain-free in contrast to placebo treated (33.1%; p=0.039) or naproxen treated (36.9%; p=0.22) [corrected] patients. Improvement in secondary outcome variables was generally superior in the HA group compared to those receiving placebo and was significantly better at Week 26 with respect to the WOMAC pain (p=0.041) and WOMAC physical function (p=0.047) subscales. The HA group also tended to have better results relative to the naproxen group in both primary and secondary assessments. For all randomized patients, there was a > or = 20 mm improvement in pain experienced on the 50 foot walk in 28% [corrected] of placebo treated patients vs 36% [corrected] of the HA treated patients (p=0.127; 67% of patients completed the trial). Injection site pain, more commonly reported in the HA group (38/164=23%) than in the placebo group (22/168=13%; p < 0.001), resulted in withdrawal in 6 patients (4%). One withdrawal was associated with the HA injection (< 1%). Gastrointestinal adverse events were significantly more common in the naproxen group than the HA or the placebo groups and 14 naproxen treated patients (8.3%) discontinued prematurely due to these events. CONCLUSION: This large, controlled randomized clinical trial confirms that 5 weekly IA injections of HA (Hyalgan) in patients with OA of the knee are generally well tolerated, provide sustained relief of pain and improved patient function, and were at least as effective with fewer adverse reactions as continuous treatment with naproxen for 26 weeks.
OBJECTIVES: We examined the efficacy, safety and patient satisfaction of intra-articular hyaluronic acid (HA) in patients with osteoarthritis of the knee. METHODS: One hundred patients with mild to moderate osteoarthritis of the knee entered a randomized blind-observer trial of 6 months HA vs placebo. Primary efficacy criteria were pain on walking, measured with a visual analogue scale, and the Lequesne Index. RESULTS: For pain on walking, a significant difference in favour of HA was found for completed patients at week 5, the end of the course of injections, and at month 6, the end of the study (P = 0.0087 and P = 0.0049, respectively). Further analysis using the Last Observation Carried Forward (LOCF) also showed a significant benefit favouring HA at month 6 (P = 0.0010). For the Lequesne Index, a significant difference in favour of HA was found at week 5 (P = 0.030) and at month 2 (P = 0.0431), but this was only of borderline significance at month 4 (P = 0.0528). Patients' global assessment of efficacy favoured HA at month 6 (P = 0.012). Improvement in other secondary criteria was generally superior in the HA group compared to placebo both at week 5 and month 6. Adverse events, mainly local injection site reactions, occurred in both groups with equal frequency. CONCLUSIONS: The study demonstrated that five weekly intra-articular injections of sodium hyaluronate (Hyalgan) were superior to placebo and well tolerated in patients with osteoarthritis of the knee with a symptomatic benefit which persisted for 6 months.
Hylan G-F 20, which is derived from hyaluronan, is a highly purified, elastoviscous fluid with rheologic properties similar to those of synovial fluid in the knee joints of healthy young persons. The efficacy and safety of viscosupplementation with hylan G-F 20 were evaluated in a multicenter, double-masked clinical study in patients with chronic idiopathic osteoarthritis (OA) of the knee of 1 to 30 years' duration. Three intra-articular injections of 2 mL hylan G-F 20 were administered 1 week apart to 57 knees. The control group (60 knees) received 2 mL of physiologic buffered saline solution at the same intervals. Patients were predominantly female (65%), with a mean age of 62 years and mean weight of 76 kg. Using a visual analogue scale, patients assessed the following clinical variables: pain during weight-bearing, pain at rest during the night, reduction of pain during the most painful movement of the knee, and treatment success. Evaluators also assessed patients' loss of activity while performing difficult daily tasks and treatment success. There was dramatic early improvement in all six variables with hylan G-F 20 beginning after the first injection; the improvement continued through the study end points. The differences between hylan G-F 20 and saline treatment were statistically significant for all outcome measures. In the hylan G-F 20 group, 39% to 56% of patients were free or nearly free of weight-bearing pain 10 to 24 weeks after the last injection. Treatment with saline was less effective, with fewer than 13% of patients free or nearly free of weight-bearing pain. Use of rescue therapy was significantly greater in the saline group than in the hylan G-F 20 group. No adverse events were observed in the injected joint after hylan G-F 20 treatment. These results demonstrate that hylan G-F 20 is effective and well tolerated in the management of chronic idiopathic OA.
BACKGROUND: At this time, no definite treatment exists for osteoarthritis disease. Hyaluronate (ARTZ) is one of the most important components of synovial fluid. It is generally accepted that hyaluronic acid protects the articular cartilage and soft tissue surfaces from trauma during joint function. METHODS: Ninety patients with 116 knees diagnosed as early arthritis (mild to moderate) by four senior orthopaedic surgeons were selected to join this study. The trial design was applied with a double-blind model. The selected patients were randomly injected with 2.5 ml drugs (ARTZ or placebo) intra-articularly once a week for five consecutive weeks without the use of local anesthetic drugs. Evaluation results included grading of subjective and objective symptoms and daily activities. The follow-up period was up to six months after initial injection. RESULTS: According to the results of clinical evaluation and statistical analysis, SPH (ARTZ) is quite effective for osteoarthritis knees, and significantly better than the placebo. The effective peak was one week after five injections of ARTZ. The effective period could last up to three months without additional treatment. The efficacy of ARTZ on osteoarthritis knees was more prominent for relief of motion pain and improvement of knee movement. No side effects developed during a six month period. CONCLUSIONS: Based on clinical results here, SPH is a safe drug for administration as an alternative approach to treat the osteoarthritis knee.
Hyaluronic acid is a natural component of cartilage and is considered not only as a lubricant in joints but also as playing a physiological role in the trophic status of cartilage. Hyalectin, a selected fraction of hyaluronic acid extracted from cocks' combs, has exhibited efficacy in animal models of osteoarthritis. To assess the efficacy and tolerability of intra-articular injections of hyalectin, we conducted a prospective, randomized, placebo-controlled trial of 1 years' duration in 110 patients with painful hydarthrodial osteoarthritis of the knee. At entry and once a week for 3 weeks, aspiration of the knee effusion and intra-articular injections of either hyalectin 20 mg (H) or its vehicle (C) were performed. The vehicle acted as the control treatment. Four weeks after the last injection, the improvement was greater in the H group compared with the C group (pain: -35.5 +/- 26.4 mm vs -25.8 +/- 21.4, P = 0.03, Lequesne's functional index: -3.8 +/- 4.3 vs -2.3 +/- 3.3, P = 0.03). During the 1 year follow-up, the need to perform supplementary local therapies (joint fluid aspiration because of painful hydarthrodial episodes and/or local corticosteroid injections) was more frequent in group C (44% vs 30%, P = 0.03). Moreover, at the final visit, the physician's overall assessment of efficacy was in favor of H (77% vs 54%, P = 0.01) and the improvement in the functional index was greater in group H (-4.4 +/- 5.1 vs -2.7 +/- 4.1, P = 0.05). This study suggests that intra-articular injections of hyalectin may (1) improve clinical condition and (2) have a long-term beneficial effect in patients with osteoarthritis of the knee.
OBJECTIVE: To assess the effects of intra-articular injections of hyaluronan on symptoms of knee osteoarthritis (OA). METHODS: Two hundred and forty patients with symptomatic, radiological knee OA were randomly assigned to treatment with weekly injections for five weeks with either 25 mg of high molecular weight hyaluronan or vehicle. Results were evaluated at weeks 1, 2, 3, 4, 5, 13, and 20 by visual analogue scales (pain, function, motion, activity), algofunctional index, and global evaluation by patient and investigator. Analysis was by "intention to treat', "per protocol', and area under the curve principles on unstratified patient groups and for patients stratified into four groups of equal size by age and baseline algofunctional index. RESULTS: No serious side effects were reported. At 20 weeks both treatment groups were improved compared with baseline, with no difference between unstratified groups treated with placebo or hyaluronan. Comparison of treatment groups stratified by age and baseline algofunctional index revealed a significant difference in favour of hyaluronan over placebo (pain, activity, algofunctional index, global evaluations by patient and investigator) for patients older than 60 years and with a baseline algofunctional index greater than 10. There was no clinically relevant difference between the two treatments for the other three stratified subgroups of younger age or fewer symptoms. Similar results were obtained by area under the curve, intention to treat, and per protocol analysis. CONCLUSIONS: Patients older than 60 years with knee osteoarthritis and with significant symptoms corresponding to an index of severity of knee disease of 10 or more, comprise the group most likely to benefit from treatment with intra-articular hyaluronan injections.
Hyaluronic acid (HA) polymers have been found to be useful as viscosupplements for the treatment of osteoarthritis (OA) in a number of clinical studies. It appears that HA with high molecular weights (HMW) are more effective than low molecular weight HA polymers.
METHODS:
A single blind, initial randomized study was conducted involving two randomly selected patient groups, which received injections of either placebo or BioHy, a highly purified HMW HA produced by bacterial fermentation. HA was administered intra-articularly and several functional tests, including pain level, stiffness, and physical function, were used to score efficacy at various intervals throughout the study.
RESULTS AND CONCLUSION:
The results through week 20 indicate that BioHy provides relief for osteoarthritic patients without causing adverse effects, although the study was not sufficiently powered to obtain statistically significant differences between the treatment groups.
