Safety and effectiveness assessment of intravenous immunoglobulin in the treatment of relapsing-remitting multiple sclerosis: A meta-analysis

Background: Intravenous immunoglobulin (IVIG) is an established treatment of immune mediated demyelinating neuropathy including Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. Recent trials suggest its efficacy in treating relapsing- remitting multiple sclerosis. IVIG exerts a number of effects, which may be beneficial in treating multiple sclerosis (MS): Reduction of inflammation, inhibition of macrophages, and promotion of remyelination. The aim of this study was to provide an overall assessment of the existing trials of safety and effectiveness of IVIG in relapsing- remitting MS compared to other drugs currently available for the treatment of disease activity in MS.   Methods: A systematic search strategy was applied to MEDLINE (PubMed and Ovid Medline (1990- Nov 2014)), Cochrane Library 2014, and Trip Database 2014, CRD. The reference lists from the identified trials, MS clinical handbooks and guidelines for the use of IVIG were studied. This article was conducted without language restrictions. Randomized controlled trials of IVIG in MS were selected. Sixteen double-blinded trails were randomly selected. Ten trials were excluded and we performed a meta-analysis on the six trials (537 participants) of IVIG in comparison to placebo. The methodological quality of the trials was assessed using Jadad checklist.   Results: The meta-analysis showed a significant beneficial effect on proportion of relapse-free patients (OR: 1.693; 95% CI-1.205-2.380), on the proportion of patients who improved (OR:2.977; 95% CI 1.769-5.010; p=0.0001) and deteriorated (OR:0.522; 95% CI0.330-0.827; p=0.006) between placebo and IVIG-treated patients. In addition, there was a reduction in the annual relapse rate in the IVIG group compared to placebo, which was statistically significant (SMD=-0.218; 95% CI-0.412 to -0.024; p=0.028). The results of the meta-analysis did not show significant differences between Expanded Disability Status Scale (EDSS) changes from baseline (SMD,-0.025; 95% CI,-0.211 to 0.161; p=0.860).    Conclusion: IVIG can be considered as an alternative therapeutic option, second-line therapy or adjuvant therapy, considering its beneficial effects (high tolerance, need to be injected with longer intervals, etc.) for treating relapsing–remitting MS patients.