Intravenous immunoglobulin treatment in multiple sclerosis Effect on relapses

Multiple Sclerosis Center, Sheba Medical Center, Tel Hashomer, Israel.
Neurology (Impact Factor: 8.29). 03/1998; 50(2):398-402. DOI: 10.1212/WNL.50.2.398
Source: PubMed


We conducted a double-blind, placebo-controlled study of 40 patients (aged 19 to 60 years) with clinical definite relapsing remitting (RR) MS and brain MRI confirmed. Patients were randomly assigned to receive a loading dose of immunoglobulin IgG (0.4 g/kg/body weight per day for 5 consecutive days), followed by single booster doses (0.4 g/kg/body weight) or placebo once every 2 months for 2 years. The primary outcome measures were change in the yearly exacerbation rate (YER), proportion of exacerbation-free patients, and time until first exacerbation. Neurologic disability, exacerbation severity, and changes in brain MRI lesion score were the secondary outcome measures, all determined at baseline, 1 year, and on completion. Treated patients showed a reduction in YER from 1.85 to 0.75 after 1 year and 0.42 after 2 years versus 1.55 to 1.8 after 1 year and to 1.4 after 2 years in the placebo group (p = 0.0006, overall), reflecting a 38.6% reduction in relapse rate. Six patients in the IVIg group were exacerbation free throughout the 2-year period of the study, whereas none were exacerbation free in the placebo group. The median time to first exacerbation was 233 days in the IVIg group versus 82 days in the placebo group (p = 0.003). Neurologic disability as measured by the Expanded Disability Status Scale (EDSS score) decreased by 0.3 in the IVIg group and increased by 0.15 in the placebo group. Total lesion score evaluated by brain MRI did not show a significant difference between groups. Side effects were minor and occurred in only 19 of 630 (3.0%) infusions administered in both groups. Our results suggest that IVIg may be safe and effective in reducing the frequency of exacerbations in RR-MS.

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Available from: Uri Gabbay, Oct 05, 2015
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    • "While several studies have suggested a beneficial effect of intravenous immunoglobulin (IVIG) in RRMS [Fazekas et al. 1997; Achiron et al. 1998; Lewanska et al. 2002] and CIS [Achiron et al. 2004] in terms of relapse rate, MRI and disability progression, there were limitations in terms of methodology and sample size. The most recent published trial from the Prevention of Relapse with Intravenous Immunoglobulin (PRIVIG) study group brought the efficacy of IVIG as a preventative agent in MS into question [Fazekas et al. 2008]. "
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    ABSTRACT: Multiple sclerosis (MS) is a potentially disabling chronic autoimmune neurological disease that mainly affects young adults. Our understanding of the pathophysiology of MS has significantly advanced in the past quarter of a century. This has led to the development of many disease-modifying therapies (DMTs) that prevent exacerbations and new lesions in patients with relapsing remitting MS (RRMS). So far there is no drug available that can completely halt the neurodegenerative changes associated with the disease. It is the purpose of this review to provide concise information regarding mechanism of action, indications, side effects and safety of Food and Drug Administration and European Medicines Agency approved agents for MS, emerging therapies, and drugs that can be considered for off-label use in MS.
    Therapeutic Advances in Neurological Disorders 07/2012; 5(4):205-20. DOI:10.1177/1756285612450936 · 3.14 Impact Factor
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    • "A study published by Ephrem et al. in Blood also demonstrated that IVIg therapy induced expansion of Tregs and protected against development of EAE induced by active immunization with myelin oligodendrocyte glycoprotein (MOG)35–55 [43]. IVIg has been considered as a potential systemic therapy for MS and other autoimmune diseases [44, 45]; however, the use of human IVIg is associated with a number of real and potential adverse effects [46, 47]. In order to explore a safer, more effective alternative to IVIg for the treatment of MS, we have evaluated the capacity of IgG-derived Tregitopes to generate antigen-specific adaptive tolerance induction to MOG35–55 epitopes in vivo. "
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    ABSTRACT: The induction of immunologic tolerance is an important clinical goal in autoimmunity. CD4(+) regulatory T (Treg) cells, defined by the expression of the transcription factor forkhead box P3 (FoxP3), play a central role in the control of autoimmune responses. Quantitative and qualitative defects of Tregs have been postulated to contribute to failed immune regulation in multiple sclerosis (MS) and other autoimmune diseases. This paper highlights the potential uses of T regulatory cell epitopes (Tregitopes), natural Treg epitopes found to be contained in human immunoglobulins, as immunomodulating agents in MS. Tregitopes expand Treg cells and induce "adaptive Tregs" resulting in immunosuppression and, therefore, are being considered as a potential therapy for autoimmune diseases. We will compare Tregitopes versus intravenous immunoglobulin (IVIg) in the treatment of EAE with emphasis on the potential applications of Tregitope for the treatment of MS.
    Neurology Research International 09/2011; 2011(1):256460. DOI:10.1155/2011/256460
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    • "21 1984 0.82 RRMS 24 Lewan´ska M et al. 22 2002 1.24 RRMS 24 Lycke J et al. 23 1996 1.57 RRMS 24 Myhr KM et al. 24 1999 0.88 RRMS 24 Oger J et al. 25 2005 0.60 RRMS 24 Polman C et al. 26 2006 0.73 RRMS 24 PRISMS Study Group 27 2001 1.02 RRMS 24 Filippi M et al. 28 2006 0.61 RRMS 48 Hauser SL et al. 29 2008 0.84 RRMS 48 Comi G et al. 30 2008 0.77 RRMS 48 Fazekas F et al. 31 2008 0.50 RRMS 48 Fazekas F et al. 32 1997 1.26 RRMS 48 Comi G et al. 33 2001 1.21 RRMS 48 Johnson KP et al. 34 1998 0.81 RRMS 48 Achiron A et al. 35 1998 1.61 RRMS 48 Goodkin DE et al. 36 1991 1.88 RRMS 48 Jacobs LD et al. 8 1996 0.82 RRMS 48 Johnson KP et al. 7 1995 0.84 RRMS 48 Millefiorini E et al. 37 1997 1.31 RRMS 48 Miller DH et al. 38 2003 0.51 RRMS 48 "
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