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.
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Acknowledgement
We should appreciate from the medical personnel and provided facilities by the Ghaem Hospital in Mashhad, Loghman Hakim Hospital, Imam Khomeini Hospital, Imam Hossein Hospital in Tehran, Shahid Sadoughi Hospital in Yazd and Department of Rheumatology at Pakistan Institute of Medical Sciences in Islamabad, Pakistan.
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Rezaieyazdi, Z., Farooqi, A., Soleymani-Salehabadi, H. et al. International multicenter randomized, placebo-controlled phase III clinical trial of β-d-mannuronic acid in rheumatoid arthritis patients. Inflammopharmacol 27, 911–921 (2019). https://doi.org/10.1007/s10787-018-00557-2
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DOI: https://doi.org/10.1007/s10787-018-00557-2