Rituximab in the treatment of polyneuropathy associated with anti‐MAG antibodies

Renaud, Susanne; Gregor, Michael; Fuhr, Peter; Lorenz, Delia; Deuschl, Günther; Gratwohl, Aloïs; Steck, Andreas

doi:10.1002/mus.10359

Cited by 178 publications

(109 citation statements)

References 17 publications

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“…Our results confirmed the median change in B-cell and CD20 cell counts reported in previous studies, 14,15,18 but it is unclear whether this reflects the beneficial effect of rituximab in IgM anti-MAG demyelinating neuropathy. It would be important to determine levels of B-cell-activating factor (BAFF), which controls B-cell homeostasis, to further understand the role of these cells in treatment.…”

supporting

confidence: 90%

“…12,13 Rituximab is a genetically engineered chimeric murine/human monoclonal antibody directed against CD20, a protein present on the surface of normal and malignant pre-B and mature B cells until differentiation into plasma cells. Efficacy of rituximab has been supported by both uncontrolled studies [14][15][16][17] and, more recently, an RCT that concluded there was a small difference between rituximab and placebo-treated patients, 18 although confirmation is needed in a larger trial. The aim of the Rituximab vs Placebo in Polyneuropathy Associated With Anti-MAG IgM Monoclonal Gammopathy (RIMAG) study was to test the hypothesis that rituximab at 375 mg/m 2 is beneficial in patients with IgM anti-MAG demyelinating neuropathy.…”

mentioning

confidence: 99%

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Placebo-controlled trial of rituximab in IgM anti-myelin–associated glycoprotein neuropathy

et al. 2013

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Objective: To determine whether rituximab 375 mg/m 2 was efficacious in patients with immunoglobulin M (IgM) anti-myelin-associated glycoprotein antibody demyelinating neuropathy (IgM anti-MAG demyelinating neuropathy).Methods: Fifty-four patients with IgM anti-MAG demyelinating neuropathy were enrolled in this randomized, double-blind, placebo-controlled trial. The inclusion criteria were inflammatory neuropathy cause and treatment (INCAT) sensory score (ISS) $4 and visual analog pain scale .4 or ataxia score $2. The primary outcome was mean change in ISS at 12 months.Results: Twenty-six patients were randomized to a group receiving 4 weekly infusions of 375 mg/m 2 rituximab, and 28 patients to placebo. Intention-to-treat analysis, with imputation of missing ISS values by the last observation carried forward method, showed a lack of mean change in ISS at 12 months, 1.0 6 2.7 in the rituximab group, and 1.0 6 2.8 in the placebo group. However, changes were observed, in per protocol analysis at 12 months, for the number of patients with an improvement of at least 2 points in the INCAT disability scale (p 5 0.027), the self-evaluation scale (p 5 0.016), and 2 subscores of the Short Form-36 questionnaire. Within the spectrum of chronic immune-mediated neuropathies, demyelinating neuropathy associated with immunoglobulin M (IgM) monoclonal gammopathy and antibodies against myelin-associated glycoprotein (MAG) is a distinct entity that typically presents with progressive sensory ataxia and painful paresthesias.1-8 Patients present with a striking immunochemical profile, suggesting the possibility of an autoimmune mechanism: monoclonal IgM recognizes a carbohydrate MAG epitope, which is shared with a number of other glycoconjugates involved in cell adhesion, including the Po glycoprotein of myelin, peripheral myelin protein-22, sulfated sphingolipid, and other related glycolipids.9,10 The disease may progress slowly over many years in some patients, whereas others develop significant disability mostly due to dysesthesias and ataxia; thus, there is a need to develop effective treatments.

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supporting

confidence: 90%

mentioning

confidence: 99%

Placebo-controlled trial of rituximab in IgM anti-myelin–associated glycoprotein neuropathy

et al. 2013

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“…On the basis of these results, Rituximab was approved in 2006 for use in RA patients who do not respond to TNF-antagonists (Sabahi and Anolik, 2006). Rituximab has also shown benefit in several other autoimmune diseases, including autoantibody-associated neuropathies, immune thrombocytopenia and systemic lupus erythematosus (Edwards and Cambridge, 2006;Renaud et al, 2003Renaud et al, , 2006Sabahi and Anolik, 2006;Tanaka et al, 2007).…”

Section: Therapeutic Depletion Of B Cells In Ms With Rituximabmentioning

confidence: 99%

Chapter 4 B Cells and Autoantibodies in the Pathogenesis of Multiple Sclerosis and Related Inflammatory Demyelinating Diseases

McLaughlin

Wucherpfennig

2008

Advances in Immunology

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Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). The mainstream view is that MS is caused by an autoimmune attack of the CNS myelin by myelin-specific CD4 T cells, and this perspective is supported by extensive work in the experimental autoimmune encephalomyelitis (EAE) model of MS as well as immunological and genetic studies in humans. However, it is important to keep in mind that other cell populations of the immune system are also essential in the complex series of events leading to MS, as exemplified by the profound clinical efficacy of B cell depletion with Rituximab. This review discusses the mechanisms by which B cells contribute to the pathogenesis of MS and dissects their role as antigen-presenting cells (APCs) to T cells with matching antigen specificity, the production of proinflammatory cytokines and chemokines, as well as the secretion of autoantibodies that target structures on the myelin sheath and the axon. Mechanistic dissection of the interplay between T cells and B cells in MS may permit the development of B cell based therapies that do not require depletion of this important cell population.

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“…55,56 In a phase II, 12-month pilot study, nine patients with anti-MAG neuropathy who were resistant to other therapies were treated with rituximab 375 mg/m 2 . 57 This study demonstrated clinical improvement in six of the nine patients by at least 2 points on the neurological disability score, and seven had improved nerve conduction studies by at least 10%. There was laboratory evidence of reduction of B cells, anti-MAG antibodies, and total IgM.…”

Section: Therapy Of Anti-myelin-associated Glycoprotein Polyneuropathymentioning

confidence: 52%

Inflammatory Demyelinating Neuropathies and Neuropathies Associated with Monoclonal Gammopathies: Treatment Update

2008

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Summary:This review focuses on recent data regarding inflammatory demyelinating neuropathies and neuropathies associated with monoclonal gammopathies. We describe both acute and chronic inflammatory neuropathies, and we discuss conditions ranging from mostly cell-mediated to antibody-mediated disorders. These diseases are characterized by proximal and distal sensory motor involvement. Treatments are based on immune-modulation and/or immune-suppression. Work-up sequence and therapeutical modes are discussed in the light of recently published data, with a special interest on new treatment modalities.

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Rituximab in the treatment of polyneuropathy associated with anti‐MAG antibodies

Cited by 178 publications

References 17 publications

Placebo-controlled trial of rituximab in IgM anti-myelin–associated glycoprotein neuropathy

Placebo-controlled trial of rituximab in IgM anti-myelin–associated glycoprotein neuropathy

Chapter 4 B Cells and Autoantibodies in the Pathogenesis of Multiple Sclerosis and Related Inflammatory Demyelinating Diseases

Inflammatory Demyelinating Neuropathies and Neuropathies Associated with Monoclonal Gammopathies: Treatment Update

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