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International Multicenter Randomized, Placebo-Controlled Phase Iii Clinical Trial of Β-D-Mannuronic Acid in Rheumatoid Arthritis Patients Publisher Pubmed



Rezaieyazdi Z1 ; Farooqi A2 ; Soleymanisalehabadi H3 ; Ahmadzadeh A4 ; Aslani M5 ; Omidian S5 ; Sadoughi A5 ; Vahidi Z6 ; Khodashahi M1 ; Zamurrad S2 ; Mortazavijahromi SS5 ; Fallahzadeh H7 ; Hosseini M8 ; Aghazadeh Z5 Show All Authors
Authors
  1. Rezaieyazdi Z1
  2. Farooqi A2
  3. Soleymanisalehabadi H3
  4. Ahmadzadeh A4
  5. Aslani M5
  6. Omidian S5
  7. Sadoughi A5
  8. Vahidi Z6
  9. Khodashahi M1
  10. Zamurrad S2
  11. Mortazavijahromi SS5
  12. Fallahzadeh H7
  13. Hosseini M8
  14. Aghazadeh Z5
  15. Ekhtiari P5
  16. Matsuo H9
  17. Rehm BHA10
  18. Cuzzocrea S11
  19. Daniello A12
  20. Mirshafiey A5
Show Affiliations
Authors Affiliations
  1. 1. Rheumatic Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
  2. 2. Department of Rheumatology, Pakistan Institute of Medical Sciences, Islamabad, Pakistan
  3. 3. Department of Rheumatology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  4. 4. Department of Rheumatology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  5. 5. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Box: 14155-6446, Tehran, Iran
  6. 6. Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  7. 7. Research Center of Prevention and Epidemiology of Non-Communicable Disease, Departments of Biostatistics and Epidemiology, Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  8. 8. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Nagasaki National Hospital, Sakuragi-cho 6-41, Nagasaki, Japan
  10. 10. Centre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith University, Nathan, QLD, Australia
  11. 11. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
  12. 12. Laboratory of Neurobiology, Zoological Station of Naples “Anton Dohrn�, Villa Comunale, Naples, Italy

Source: Inflammopharmacology Published:2019


Abstract

Background: The oral administration of drug β-d-mannuronic acid (M2000) showed a potent therapeutic effect in phase I/II study in rheumatoid arthritis (RA) patients. Here, our aim is to assess the efficacy and safety of this new drug in RA patients under a multinational, randomized placebo-controlled phase III clinical trial. Method: Patients (n = 288) with active disease at baseline and inadequate response to conventional drugs were randomly allocated to three groups; (1) receiving mannuronic acid at a dose of two capsules (500 mg) per day orally for 12 weeks, (2) placebo-controlled, and (3) conventional. The primary endpoints were the America College of Rheumatology 20 response (ACR20), 28-joint disease activity score (DAS28) and Modified Health Assessment Questionnaire-Disability Index (M-HAQ-DI). In addition, the participants were followed-up for safety assessment. Results: In this phase III trial, after 12 weeks of treatment, there was a significant reduction in ACR20 between mannuronic-treated patients compared to placebo and conventional groups. Moreover, there was a similar significant improvement for DAS28 following mannuronic therapy. The statistical analysis showed a significant reduction in the swollen and tender joint count in mannuronic-treated patients compared with the placebo group. On the other side, mannuronic acid showed no-to-very low adverse events in comparison to placebo. Conclusion: The results of this multinational, phase III clinical trial provided a potent evidence base for the use of β-d-mannuronic acid as a new highly safe and efficient drug in the treatment of RA. © 2019, Springer Nature Switzerland AG.
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