A phase I/II randomized, controlled, clinical trial for assessment of the efficacy and safety of β-d-mannuronic acid in rheumatoid arthritis patients

Background: Following the potent efficacy of [ì-o-mannuronic acid (M2000) in phase I/Il trial in ankylosing spondylitis patients, the present clinica] tria! was conducted to evaluate the efficacy, safety, and tolerability of this nove! drug in rheumatoid arthritis (RA) patients who had inadequate response to conventional therapy. Method: The study was a 12-week randomized, controlled, phase I/II clinica! tria! with two treatment arms: M2000 and conventional treatment. Patients who had RA according to the modifìed American College of Rheumatology (ACR) criteria, with active disease at baseline also inadequate response to conventional therapy, were enrolled in this study, M2000 was administrated at a dose of two capsules (500 mg) per day orally during a period of 12 weeks. The primary endpoint was the proportion of patients fulfìlling the ACR 20% improvement criteria after 12 weeks of M2000 therapy. Moreover, the patients were also followed up for safety. Results: There were no statistically signifìcant differences between treatment and conventional groups at baseline characteristics. The ACR20 response rate was signifìcantly higher among M2000-treated patients than conventional-treated contro!, so that 74% of patients in treatment group showed an ACR20 response after 12 weeks of M2000 therapy (74 versus 16%; P= O.O 11 ). I 0% of M2000-treated patients and 57.1 % of conventional-treated patient's ad verse events occurred during this study. Conclusion: Treatment with M2000 in combination with conventionaJ therapy showed a significantly superior efficacy along with a high safety profìle compared to conventional-treated patients. Thereby, M2000 might be suggested as a suitable option in the treatment of RA.