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A Phase I/Ii Randomized, Controlled, Clinical Trial for Assessment of the Efficacy and Safety of Β-D-Mannuronic Acid in Rheumatoid Arthritis Patients Publisher Pubmed



Ahmadi H1 ; Jamshidi AR2 ; Gharibdoost F2 ; Mahmoudi M2 ; Rastkari N3 ; Mostafaei S2 ; Fattahi MJ1, 9 ; Vojdanian M2 ; Cuzzocrea S4 ; Rehm BHA5 ; Matsuo H6, 7 ; Hosseini M8 ; Aghazadeh Z1 ; Mortazavijahromi SS1, 10 Show All Authors
Authors
  1. Ahmadi H1
  2. Jamshidi AR2
  3. Gharibdoost F2
  4. Mahmoudi M2
  5. Rastkari N3
  6. Mostafaei S2
  7. Fattahi MJ1, 9
  8. Vojdanian M2
  9. Cuzzocrea S4
  10. Rehm BHA5
  11. Matsuo H6, 7
  12. Hosseini M8
  13. Aghazadeh Z1
  14. Mortazavijahromi SS1, 10
  15. Mirshafiey A1
Show Affiliations
Authors Affiliations
  1. 1. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Box: 14155-6446, Tehran, Iran
  2. 2. Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Center for Air Pollution Research (CAPR), Institute for Environmental Research (IER), Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
  5. 5. Centre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith University, Nathan, QLD, Australia
  6. 6. Department of Clinical Research, Nagasaki Kawatana Medical Center, Nagasaki, Japan
  7. 7. Department of Neurology, Nagasaki Kawatana Medical Center, Nagasaki, Japan
  8. 8. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  10. 10. Department of Cellular and Molecular Biology, Kish International Campus, University of Tehran, Kish, Iran

Source: Inflammopharmacology Published:2018


Abstract

Background: Following the potent efficacy of β-d-mannuronic acid (M2000) in phase I/II trial in ankylosing spondylitis patients, the present clinical trial was conducted to evaluate the efficacy, safety, and tolerability of this novel 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 clinical trial with two treatment arms: M2000 and conventional treatment. Patients who had RA according to the modified 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 fulfilling 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 significant differences between treatment and conventional groups at baseline characteristics. The ACR20 response rate was significantly higher among M2000-treated patients than conventional-treated control, so that 74% of patients in treatment group showed an ACR20 response after 12 weeks of M2000 therapy (74 versus 16%; P = 0.011). 10% of M2000-treated patients and 57.1% of conventional-treated patient’s adverse events occurred during this study. Conclusion: Treatment with M2000 in combination with conventional therapy showed a significantly superior efficacy along with a high safety profile compared to conventional-treated patients. Thereby, M2000 might be suggested as a suitable option in the treatment of RA. © 2018, Springer International Publishing AG, part of Springer Nature.
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