Intravenous immunoglobulin G reduces MRI activity in relapsing multiple sclerosis

Abstract

We wanted to assess whether intravenous immunoglobulin G (IVIG) decreases disease activity on MRI in relapsing MS. Previous trials of IVIG in relapsing-remitting MS demonstrated a reduction of acute relapses, but these studies did not include MRI. We treated 26 patients in a randomized, double-blind, crossover study of IVIG 1 g/kg daily or placebo on 2 consecutive days every month during two 6-month treatment periods. The primary end point was the number of gadolinium-enhancing lesions on monthly serial MRI. Secondary efficacy variables were the occurrence of exacerbations, clinical neurologic ratings, total MS lesion load on T2-weighted MRI, and multimodal evoked potentials. Eighteen patients completed the entire trial; eight patients did not. Twenty-one patients completed the first treatment period and at least two MRI examinations in the second treatment period and were included in the intention-to-treat analysis. On serial MRI, we observed fewer enhancing lesions per patient per scan during IVIG treatment (median, 0.4; range, 0 to 9.3) than during placebo treatment (median, 1.3; range, 0.2 to 25.7; p = 0.03). During IVIG treatment, 15 patients were exacerbation free compared with only 7 on placebo (p = 0.02). The total number of exacerbations in the IVIG period was 11 and in the placebo period, 19 (not significant). None of the remaining secondary efficacy measures were significantly different between the two treatment periods. The number of adverse events, in particular eczema, was significantly higher during IVIG therapy than during placebo treatment. These results suggest that IVIG treatment is beneficial to patients with relapsing MS.

Modulation of dendritic cell development by immunoglobulin G in control subjects and multiple sclerosis patients

“…In RR-MS patients, relapse is inhibited by IVIg administration during remission [7][8][9][10]. The mechanism of action by which IVIg exerts this effect has not been elucidated, although several theories have been put forth.…”

“…Intravenous immunoglobulin (IVIg) has been reported to be an effective treatment for several autoimmune diseases [1][2][3][4][5][6][7][8][9][10]. In autoimmune diseases, IVIg may exert a therapeutic effect via multiple mechanisms, including the neutralization of autoantibodies with anti-idiotype antibodies [11], inhibition of complement-mediated damage [12,13], inhibition of inflammatory cytokine production by activated lymphocytes [14,15] and Fc receptor-mediated inhibition of inflammation [16,17].…”

Human monoclonal antibodies reactive to oligodendrocytes promote remyelination in a model of multiple sclerosis

“…Several double-blind, placebo-controlled trials with IVIg have shown some efficacy in MS (18,36,37). Polyclonal human IgM, sHIgM22, and sHIgM46 all enhanced CNS remyelination in the TMEV model as well as IVIg, suggesting that these Abs may be as effective in MS. Human mAbs that bind to OLs may have the additional benefit of direct OL stimulation.…”

“…Clinical studies in MS indicate that IVIg may be partially effective in stabilizing the disease course (18,36,37). To determine whether IVIg could promote remyelination in the TMEV model of MS, chronically infected mice were treated with a single i.p.…”

Nuclear magnetic resonance monitoring of treatment and prediction of outcome in multiple sclerosis

“…However, the latter provide a more robust assessment of therapeutic e¡ect (McFarland et al 1992;Nauta et al 1994), as the former are more susceptible to the e¡ects of selection bias and regression to the mean. Numerous positive trials using crossover and parallel group designs have been reported (Moreau et al 1994;IFNB Study Group 1995;Jacobs et al 1996;Stone et al 1995;PRISMS 1998;European Study Group 1998;Edan et al 1997;Andersen et al 1996;Karussis et al 1996;Sorensen et al 1998;Durelli et al 1994;Mancardi et al 1998;Tubridy et al 1999) (table 1).…”