Intravenous immunoglobulin in relapsing-remitting multiple sclerosis - A dose-finding trial

Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria.
Neurology (Impact Factor: 8.29). 07/2008; 71(4):265-71. DOI: 10.1212/01.wnl.0000318281.98220.6f
Source: PubMed


Several studies have reported a reduction of relapses after the long-term administration of IV immunoglobulin (IVIG) to patients with relapsing-remitting multiple sclerosis (RRMS), but they were mostly small and differed in terms of predefined outcome variables and treatment regimen. We therefore set out to test two different doses of a new formulation of immunoglobulin termed IGIV-C 10% for suppression of both clinical and MRI disease activity as well as safety.
One hundred twenty-seven patients with RRMS participated in this multicenter, randomized, double-blind, placebo-controlled trial. Forty-four and 42 patients received treatment with 0.2 and 0.4 g/kg of IGIV-C 10%, and 41 patients received an equal volume of placebo (0.1% albumin) every 4 weeks for 48 weeks. The primary endpoint was the proportion of relapse-free patients. The main secondary endpoint was lesion activity assessed by 6-weekly MRI.
Baseline variables were similar in IVIG- and placebo-treated groups. After 1 year, the proportion of relapse-free patients did not differ statistically according to treatment (IVIG 0.2 g/kg: 57%; IVIG 0.4 g/kg: 60%; placebo: 68%), and there was no difference regarding the cumulative number of unique newly active MRI lesions (median numbers: IVIG 0.2 g/kg: 8.0; IVIG 0.4 g/kg: 5.0; placebo: 7.2) after 48 weeks. There were no significant between-group differences in the rates of adverse events.
Although IV immunoglobulin (IVIG) treatment was well tolerated, this study did not substantiate a beneficial effect of IVIG in doses ranging from 0.2 to 0.4 g/kg. This result seriously questions the utility of IVIG for the treatment of relapsing-remitting multiple sclerosis.

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Available from: David K B Li, Jul 01, 2015
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    • "nt by some authors studying postnatal relapses ( Fazekas et al . , 2008 ; Hellwig et al . , 2009 ) . Some authors recommend the use of immunoglobulin as a therapeutic option for MS when usual immunomodulatory drugs are inefficient ( Dudesek & Zettl , 2006 ) . Other authors , however , question whether there is indeed a response to this treatment ( Fazekas et al . , 2008 ) and whether the price paid for it is justifiable ( Elovaara & Hietaharju , 2010 ) ."
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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]. Current guidelines from the European Federation of Neurological Societies recommend that IVIG be considered as a second-or third-line therapy in RRMS if conventional immunomodulatory therapies are not tolerated [Elovaara et al. 2008]. "
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    • "No ideal dosage was determined. Another study done by Fazekas et al. [38] showed that patients treated with IVIG (0.2-0.4 mg/kg) did not show significant improvement or relapse rate or disability compared to patients with placebo. The number of patients in each arm of this study was relatively small however and as the data on IVIG remains ambiguous it is not usually used as a first line treatment. "
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