#1
Effects Of IntraVenous ImmunoGlobulin In Relapsing/Remitting Multiple Sclerosis
Further Analyzes Of The Austrian ImmunoGlobulin In Multiple Sclerosis Study
Fazekas F, Deisenhammer F, Strasser-Fuchs S, Nahler G, Mamoli B
Mult Scler 1997 Apr;3(2):137-41
Karl-Franzens University, Dept of Neurology, Graz, Austria
PMID# 9291168
Abstract
Recently, the Austrian Immunoglobulin in Multiple Sclerosis (AIMS) study showed patients with Relapsing/Remitting Multiple Sclerosis to benefit from repeated administration of IntraVenous ImmunoGlobulin (IVIG).
To provide a more detailed understanding of IVIG's action we performed further analyzes on the time course of treatment effects and in regard to the impact of clinical disability at study entry on patients' response to medication.
The AIMS trial was a randomized, placebo-controlled, double blind, multicenter trial. It included 148 patients (IVIG: 75; placebo 73) who suffered from Relapsing/Remitting MS, were 15-65 years old and scored from 1-6 on the Expanded Disability Status Score (EDSS).
IVIG was given over 2 years in a monthly dosage of 0.15-0.2 g/kg body weight. Within the first 6 months of the trial clinical disability of IVIG treated patients improved significantly from a baseline EDSS of 3.33 +/- 1.38 to a score of 3.05 +/- 1.73 (P=0.002).
This improvement was retained over the subsequent 18 months of the trial (final EDSS: 3.09 +/- 1.62). In contrast, placebo-treated patients showed a slight trend for deterioration over the study period (baseline EDSS: 3.37 +/- 1.67; final EDSS: 3.49 +/- 1.83).
IVIG treatment was associated with a significant reduction of relapses throughout the study which was independent of the patients' disability at baseline.
The observation of clinical improvement in the early phase of IVIG medication may suggest the activation of repair mechanisms such as the promotion of ReMyelination while ImmunoRegulatory effects would be expected as the cause of fewer exacerbations throughout the AIMS study.
These hypotheses need to be tested in future trials.
#2
Intravenous ImmunoGlobulin Therapy
In Relapsing/Remitting Multiple Sclerosis
Austrian ImmunoGlobulin in Multiple Sclerosis Study Group
Fazekas F, Deisenhammer F, Strasser-Fuchs S, Nahler G, Mamoli B
Lancet 1997 Mar 1;349(9052):589-93
Karl-Franzens University, Dept of Neurology, Graz, Austria
PMID# 9057729
Abstract
Multiple Sclerosis is an AutoImmune disorder characterized by the repeated occurrence of DeMyelinating lesions within the Central Nervous System.
Uncontrolled studies and experimental evidence suggest beneficial effects of repeated administration of IntraVenous ImmunoGlobulin (IVIG) by ImmunoModulating mechanisms and induction or ReMyelination.
We aimed to investigate the efficacy of IVIG in a randomized double-blind multicenter study.
Patients with Relapsing/Remitting Multiple Sclerosis were randomly assigned a monthly dose of IVIG (0.15-0.2 g/kg bodyweight) or placebo. Duration of treatment was 2 years.
The primary outcome measures were the effect of treatment on clinical disability-measured by the absolute change in Kurtzke's Expanded Disability Status Scale (EDSS) score and the proportion of patients with improved, stable, or worse clinical disability (> or = 1.0 grade on EDSS score).
Of the 243 patients screened, 150 met our eligibility criteria and were randomly assigned to IVIG or placebo. Before the start of treatment two patients in the placebo group dropped out, so there were 75 patients in the IVIG group and 73 in the placebo group.
Intention-to-treat analysis showed that IVIG treatment had a beneficial effect on the course of clinical disability. The EDSS score decreased in the IVIG-treated patients and increased in the placebo group (-0.23 [95% CI -0.43 to -0.03] vs 0.12 [-0.13 to 0.37], p = 0.008).
In the IVIG group, the numbers of patients with improved, stable, or worse clinical disability were 23 (31%), 40 (53%), and 12 (16%) compared with ten (14%), 46 (63%), and 17 (23%) in the placebo group.
Side-effects were reported in three (4%) IVIG-treated patients and in four (5%) placebo-group patients, but were not directly linked to study medication. Monthly IVIG is an effective and well-tolerated treatment for patients with Relapsing/Remitting Multiple Sclerosis.
#3
The Austrian ImmunoGlobulin In Multiple Sclerosis (AIMS) Study: Final Analysis
Strasser-Fuchs S, Fazekas F, Deisenhammer F, Nahler G, Mamoli B.
Mult Scler 2000 Oct;6 Suppl 2:S9-13
Karl-Franzens University, Department of Neurology, Graz, Austria
PMID# 11188778
Abstract
From observational studies and positive experience in other AutoImmune Disorders it has been speculated that IntraVenous ImmunoGlobulin (IVIG) may be effective for the interval treatment of MS.
The Austrian Immunoglobulin in Multiple Sclerosis (AIMS) study was the first to test this assumption in a randomized, double-blind, placebo controlled trial of 148 patients with Relapsing/Remitting MS.
IVIG given monthly at a dosage of 0. 15-0.2 g/kg bodyweight over 2 years was associated with a significantly more favourable course of disability as measured by the EDSS (- 0.23 vs 0.12; P=0.008) and caused a significant reduction of the frequency of relapses (0.52 vs 1.26; P=0.011).
Beneficial effects on these outcome measures were already seen within 6 months of treatment and did not appear to depend on the severity of baseline disability.
IVIG treatment also had a positive effect on daily and social living according to patient' self rating on the Incapacity Status and Environmental Status Scales and was associated with a lower, though not significantly different number of hospital admissions and days spent in hospital.
These data support IVIG as an alternative treatment option for Relapsing/Remitting MS and encourage further studies to clarify the optimal usage of this substance for this indication.
#4
European Study On IntraVenous ImmunoGlobulin In Multiple Sclerosis: Results Of Magnetization Transfer Magnetic Resonance Imaging Analysis
Filippi M, Rocca MA, Pagani E, Iannucci G, Sormani MP, Fazekas F, Ropele S, Hommes OR, Comi G
Arch Neurol 2004 Sep;61(9):1409-12
Scientific Institute and University Ospedale San Raffaele, NeuroImaging Research Unit, Via Olgettina 60, 20132 Milan, Italy
PMID# 15364687
Abstract
Background
Magnetization Transfer Magnetic Resonance Imaging (MT MRI) can provide in vivo markers reflecting the severity of Multiple Sclerosis-related Brain damage occurring within and outside T2-visible lesions.
Objective
To investigate the effect of IntraVenous ImmunoGlobulin (IVIG) treatment on the accumulation of Brain damage in patients with Secondary/Progressive Multiple Sclerosis (SPMS), measured using MT MRI.
Design, Patients, and Intervention
Seventy patients with SPMS participating in the European, multicenter, randomized, double-blind, placebo-controlled trial of IVIG in SPMS underwent Brain T2-weighted and MT MRI at baseline and after 12 and 24 months.
The MT MRI scans were post-processed and analyzed to obtain MT Ratio values from T2-visible lesions and MT Ratio Histograms from the Normal-Appearing Brain Tissue (NABT).
Results
At baseline, a significant difference was found for NABT MT Ratio Histogram peak height (P =.003) between treated patients and patients receiving placebo.
No significant differences between treated patients and those receiving placebo were found for any of the considered MT MRI-derived metrics in terms of treatment x time interaction.
Nevertheless, over the 24-month period, the placebo patients experienced a 6.75% reduction of the NABT MT Ratio Histogram peak height, whereas treated patients experienced only a 0.92% reduction of the NABT MT ratio Histogram peak height.
Conclusions
This study did not show any statistically significant effect of IVIG on MT MRI quantities.
Nevertheless, the markedly different percentage change of the NABT MT Ratio Histogram peak height over time between patients receiving placebo and treated patients, suggests a possible role of IVIG treatment in preventing the loss of "truly" normal Brain Tissue in SPMS patients.
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