Open-label multicenter trial of the safety and efficacy of viscosupplementation with hylan G-F 20 (Synvisc) in primary osteoarthritis of the knee

The safety and efficacy of hylan G-F 20, a viscosupplement derived from hyaluronan, were evaluated in an open-label, 12-week, multicenter, clinical trial in patients with chronic idiopathic osteoarthritis of the knee of Larsen radiographic Grades I through TV. Three intra-articular injections of 2 mi, of hylan G-F 20 were administered 1 week apart. A total of 256 knees in 222 patients were treated, with 34 patients treated bilaterally. Patients had a mean age of 62 years, and 54% were female. Safety was assessed through clinical examination and patient reports of adverse signs and symptoms that had emerged during the study period. To assess efficacy, patients evaluated the following clinical variables using a visual analogue scale: pain during weight bearing, pain at night, pain during the most painful movement of the knee, and improvement from treatment. Physicians additionally assessed patients' reduction of activity and inactivity stiffness. No generalized systemic adverse events attributable to treatment were observed. The only local adverse events, pain and/or swelling in the injected knee, occurred at a rate per injection of 2.5%. Bilateral knee injections were given in some patients, without increased adverse reactions. Ln most cases, the local events were mild and transient and did not require treatment. Arthrocenteses were performed in four knees to remove effusions and relieve pain and swelling. Patients who received hylan G-F 20 demonstrated a statistically and clinically significant improvement beginning after the first or second injection compared with their initial scores for all outcome measures assessed; all improvements increased steadily until at least 8 weeks and were maintained through the 12-week endpoint. Depending on the outcome measure, from 34% to 81% of knees were considered symptom-free at the 12-week endpoint. Improvement occurred in patients with all grades of radiologic severity. A regimen of three weekly injections conferred a long-term (3-month) reduction of pain and improvement in knee movement in many patients. The results show that hylan G-F 20 is a well-tolerated and effective treatment for chronic idiopathic osteoarthritis.