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 hya luronan, were evaluated in an open-label, 12-week, multicenter, clinical tr ial in patients with chronic idiopathic osteoarthritis of the knee of Larse n radiographic Grades I through TV. Three intra-articular injections of 2 m i, 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 h ad a mean age of 62 years, and 54% were female. Safety was assessed through clinical examination and patient reports of adverse signs and symptoms tha t had emerged during the study period. To assess efficacy, patients evaluat ed the following clinical variables using a visual analogue scale: pain dur ing 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 obser ved. The only local adverse events, pain and/or swelling in the injected kn ee, occurred at a rate per injection of 2.5%. Bilateral knee injections wer e given in some patients, without increased adverse reactions. Ln most case s, 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 stati stically and clinically significant improvement beginning after the first o r second injection compared with their initial scores for all outcome measu res assessed; all improvements increased steadily until at least 8 weeks an d were maintained through the 12-week endpoint. Depending on the outcome me asure, from 34% to 81% of knees were considered symptom-free at the 12-week endpoint. Improvement occurred in patients with all grades of radiologic s everity. A regimen of three weekly injections conferred a long-term (3-mont h) 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.