Evaluation of the efficacy and safety of β-d-mannuronic acid in patients with ankylosing spondylitis: A 12-week randomized, placebo-controlled, phase I/II clinical trial

Abstract

ObjectiveTo evaluate the efficacy, safety and tolerability of β-d-mannuronic acid (M2000) in the treatment of ankylosing spondylitis (AS). MethodsThe study was a 12-week randomized, double-blind, placebo-controlled, phase I/II clinical trial with 3 treatment arms: placebo, β-d-mannuronic acid and naproxen. Patients who had AS according to the modified New York criteria, with active disease at baseline were eligible for study. Primary outcome measure was the Assessment of SpondyloArthritis international Society (ASAS) 20 response rate at week 12. ResultsOf the 85 randomized patients, 27 were allocated to receive placebo, 28 naproxen, and 30 β-d-mannuronic acid. There were no statistically significant differences between treatment groups at baseline. Of the patients receiving β-d-mannuronic acid, 57.7% achieved an ASAS20 response at week 12, compared with 59% of the patients in the naproxen group (P>0.05) and 19% of the patients in the placebo group (P=0.007). In comparison with patients receiving placebo over the 12-week treatment period, those receiving β-d-mannuronic acid and naproxen demonstrated statistically significantly greater improvement in all secondary endpoints. Interestingly, β-d-mannuronic acid reduced some parameters associated with inflammation more effectively than naproxen and placebo. The incidence of gastrointestinal and other adverse events were higher on naproxen than on β-d-mannuronic acid and placebo. ConclusionThe present study demonstrated similar efficacy, but with a more favorable safety profile for β-d-mannuronic acid than naproxen and, therefore, suggest that β-d-mannuronic acid is suitable for the management of AS. Trial registrationIranian registry of clinical trials; www.irct.ir; IRCT2013062213739N1.