Zahra Rezaieyazdi1, Abid Farooqi2, Hossein Soleymani-Salehabadi3, Arman Ahmadzadeh4, Mona Aslani5, Saiedeh Omidian5, Arezoo Sadoughi5, Zohreh Vahidi6, Mandana Khodashahi1, Shazia Zamurrad2, Seyed Shahabeddin Mortazavi-Jahromi5, Hossein Fallahzadeh7, Mostafa Hosseini8, Zahra Aghazadeh5, Parvin Ekhtiari5, Hidenori Matsuo9, Bernd H A Rehm10, Salvatore Cuzzocrea11, Antimo D'Aniello12, Abbas Mirshafiey13. 1. Rheumatic Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Department of Rheumatology, Pakistan Institute of Medical Sciences, Islamabad, Pakistan. 3. Department of Rheumatology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. 4. Department of Rheumatology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 5. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Box: 14155-6446, Tehran, Iran. 6. Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 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. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. 9. Nagasaki National Hospital, Sakuragi-cho 6-41, Nagasaki, Japan. 10. Centre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith University, Nathan, QLD, Australia. 11. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy. 12. Laboratory of Neurobiology, Zoological Station of Naples "Anton Dohrn", Villa Comunale, Naples, Italy. 13. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Box: 14155-6446, Tehran, Iran. mirshafiey@tums.ac.ir.
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.
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.
Authors: Daniel Aletaha; Tuhina Neogi; Alan J Silman; Julia Funovits; David T Felson; Clifton O Bingham; Neal S Birnbaum; Gerd R Burmester; Vivian P Bykerk; Marc D Cohen; Bernard Combe; Karen H Costenbader; Maxime Dougados; Paul Emery; Gianfranco Ferraccioli; Johanna M W Hazes; Kathryn Hobbs; Tom W J Huizinga; Arthur Kavanaugh; Jonathan Kay; Tore K Kvien; Timothy Laing; Philip Mease; Henri A Ménard; Larry W Moreland; Raymond L Naden; Theodore Pincus; Josef S Smolen; Ewa Stanislawska-Biernat; Deborah Symmons; Paul P Tak; Katherine S Upchurch; Jirí Vencovský; Frederick Wolfe; Gillian Hawker Journal: Arthritis Rheum Date: 2010-09
Authors: Kevin D Deane; M Kristen Demoruelle; Lindsay B Kelmenson; Kristine A Kuhn; Jill M Norris; V Michael Holers Journal: Best Pract Res Clin Rheumatol Date: 2017-09-18 Impact factor: 4.098