A MULTI-CENTER RANDOMIZED COMPARATIVE PHASE IV CLINICAL DOSE-RESPONSE STUDY OF HIGH MOLECULAR WEIGHT HYALURONIC ACID (SUVENYL) ON KNEE PAIN IN RHEUMATOID ARTHRITIS

Background: Suvenyl is a non-crosslinked high molecular weight hyaluronan (HA) similar to native joint fluid HA obtained from a bacterial fermentation process, with an average molecular weight of 1900 kDa, which has been clinically used in Japan since 2000 for the world''s first approved indication of knee rheumatoid arthritis (RA) in addition to 2 indications of knee osteoarthritis and periarthritis scapulohumeralis. Suvenyl has been so far reported to improve joint fluid viscoelasticity and lubrication, and inhibit articular cartilage degeneration and inflammatory synovial proliferation in a molecular weight of HA dependent manner. In a Phase II open study, it had been also demonstrated that the 1% Suvenyl-treated group had greater efficacy for knee RA than 0.6% Suvenyl-treated group, and the plateau of efficacy is gained after 5 weekly injections. Together with the result of a Phase III study, the optimal efficacy of Suvenyl was observed when the patients received 5 weekly 2.5ml intraarticular injections of 1% Suvenyl.Objectives: The objective of this Phase IV study is to precisely reconfirm the dose-response relationship for knee RA in 1% versus 0.6% Suvenyl-treated groups.Methods: 286 patients fulfilling the ACR criteria 1987 for RA were enrolled in this study by 30 medical facilities. The patients were also selected from those whose knee''s symptoms were assessed as mild to moderate cases showing a CRP value less than 10mg/dl, and assigned a Larsen''s knee X-ray grade I to III. Five intraarticular injections of 2.5ml of 1% Suvenyl were performed into knee joint of patients at the interval of 1 week. Efficacy was finally evaluated at 1 week after 5 weekly injections by measuring the change of pain scores judged by physicians and the changes of a visual analogue scale (VAS) rated by patients. Statistical analyses were performed using Wilcoxon''s rank sum test and Student''s t-test for the determination of the changes of pain scores judged by physicians and changes of VAS rated by patients, respectively.Results: Of the 286 enrolled patients, Suvenyl injection was initiated in 285 patients except 1 untreated patient. 143 patients received 1% Suvenyl, and 142 patients received 0.6% Suvenyl, respectively. At the initiation of treatment of Suvenyl, the average of the total pain scores measured as the primary endpoint was same 3.7 in both groups. The changes of pain scores judged by physicians at 1 week after 5 weekly injections were -45.1% in the 1%-group and -27.3% in the 0.6%-group. There was a significant difference in the change of pain score between both groups (p=0.013). The changes of VAS rated by patients at 1 week after 5 weekly injections were -34.6% in the 1%-group and -17.2% in the 0.6%-group. Pain symptom in the 1%-group was also significantly improved compared with that in the 0.6%-group (p=0.035). Furthermore, there were no clinically serious side effects in either group.Conclusion: From these results, it was concluded that the 1%-HA group is clinically more effective for knee RA than the 0.6%-HA group as well as the dose-response curve in the Phase II study.Citation: Ann Rheum Dis, volume 64, supplement III, year 2005, page 415Session: Rheumatoid Arthritis – Treatment