ArticlesRandomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis*
Introduction
Multiple sclerosis is the most common demyelinating disorder of the central nervous system, and is characterised by repeated episodes of neurological dysfunction with variable remission. Previous studies have suggested that autoimmune mechanisms have an important role in the pathogenesis of multiple sclerosis.1, 2 Intravenous immunoglobulin (IVIg) has been successful in other autoimmune neurological disorders, such as acute and chronic inflammatory demyelinating radiculoneuropathies,3, 4 myasthenia gravis,5 and dermatomyositis.6 Yan and colleagues7 recommended IVIg treatment for acute exacerbations of multiple sclerosis and three uncontrolled or open-label studies reported a beneficial effect of long-term IVIg treatment on the course of the disease.8, 9, 10, 11 Several immunological mechanisms may be involved in multiple sclerosis.12, 13 IVIg produced from pooled blood from healthy donors may contain antiidiotypic antibodies, which have regulatory effects on antibody production and lymphocyte activity.14 IVIg may also reduce the autoaggressive effect of macrophages by blocking their Fc-receptors,15 or it may act as a receptor for activated complement components preventing their binding to the oligodendrocyte surface and myelin proteins.16 In addition, IVIg can down-regulate cytokine production and neutralise inflammatory cytokines.17 All these mechanisms are involved in the pathogenesis of multiple sclerosis lesions.
Experiments in mice have shown that IVIg may promote remyelination within demyelinative lesions induced by Theiler's virus.18 The clinical significance of this mechanism was supported by van Engelen and colleagues' study19 of five multiple sclerosis patients with optic neuritis: after a period of stable visual impairment for between 7 months and 4 years, IVIg treatment led to an increase in visual acuity and colour vision 1–2 months after the start of treatment which continued thereafter.19 This finding suggests that repeated IVIg therapy may not only delay or prevent the progression of multiple sclerosis but can even induce clinical improvement.20
Our randomised, double-blind, placebo-controlled, multicentre study was designed to assess the effect of monthly IVIg treatment on the clinical course of relapsingremitting multiple sclerosis.
Section snippets
Methods
Between December, 1992, and January, 1996, 243 patients from 13 neurological centres throughout Austria were considered for enrolment in our study.
Our definition of relapsing-remitting multiple sclerosis included individuals with complete and incomplete remissions.21 Inclusion criteria were a clinically definite diagnosis of relapsingremitting multiple sclerosis,22 a baseline Kurtzke's expanded disability status scale (EDSS)21 score of between 1·0 (minor neurological signs but no disability)
Results
Of the 243 patients screened for eligibility, 93 did not meet the inclusion criteria: 17 had an EDSS score of less than 1·0 or more than 6·0; 16 had too low progression rates; seven had had fewer than two relapses within the previous 2 years; 12 did not have relapsing-remitting multiple sclerosis; 14 were taking immunomodulatory drugs, four were not available to take part in the study; 12 did not give their consent; and 11 were excluded for other reasons. Two patients withdrew their consent to
Discussion
Our study is the first large-scale placebo-controlled trial of the efficacy of long-term IVIg treatment in relapsingremitting multiple sclerosis. Our findings show that a monthly dose of IVIg (0·15–0·20 g/kg bodyweight) improved the course of clinical disability and reduced the frequency of relapses. At the end of 2 years, the magnitude of the absolute change in EDSS score and, thus, in clinical disability was small in both groups. However, the between-group difference in absolute change in
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Efficacy of intravenous immunoglobulin in autoimmune neurological diseases. Literature systematic review and meta-analysis
2022, Autoimmunity ReviewsCitation Excerpt :Twenty-three studies that met the selection criteria were included in this study, which were classified into three categories. The first category included studies that compared the efficacy of IVIg with placebo; nine studies were analyzed, four of which focused on CIDP [82–85] and five on MS [86–90]. The second category corresponded to studies comparing the efficacy of IVIg versus plasmapheresis; nine studies were analyzed in this category, of which five focused on GBS [91–95], three on MG [96–98], and one on MS [99].
Intravenous immunoglobulins for the prevention of postpartum relapses in multiple sclerosis
2020, Multiple Sclerosis and Related DisordersUpdate on the use of immunoglobulin in human disease: A review of evidence
2017, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Combining the data from these studies showed that 34% of IVIG recipients had reduced exacerbations versus 15% of placebo recipients. The largest study (148 patients) revealed that IVIG (0.15-0.2 g/kg monthly for 2 years) was associated with reduced clinical disability.448 When larger doses were tried (1 g/kg/d for 2 days at 4-week intervals), 65% (of 25 patients) had no exacerbations in 6 months versus 35% of the control group.449
Multiple Sclerosis
2016, International Encyclopedia of Public Health
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