High efficacy of rituximab for myasthenia gravis: a comprehensive nationwide study in Austria

Topakian, Raffi; Zimprich, Fritz; Iglseder, Stephan; Embacher, Norbert; Guger, Michael; Stieglbauer, Karl; Langenscheidt, Dieter; Rath, Jakob; Quasthoff, Stefan; Simschitz, Philipp; Wanschitz, Julia; Windisch, David; Müller, P; Oel, Dierk; Schustereder, Günther; Einsiedler, Stefan; Eggers, Christian; Löscher, Wolfgang N.

doi:10.1007/s00415-019-09191-6

Cited by 62 publications

(98 citation statements)

References 29 publications

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“…Online supplementary file 1 summarises data from selected studies on the use of RTX in AChR-MG. Thirteen studies have been selected, showing good safety 1 2 6 7 9 11–18. The data collected from each report included the number and regimen of infusions used for therapy with RTX, antibody type and titres pretreatment and post-treatment, follow-up duration, data on safety and postintervention status of MG.…”

Section: Resultsmentioning

confidence: 99%

“…The presence of thymoma in AChR-MG was specified in eight studies, accounting for 34 out of 165 overall patients with AChR-MG (online supplementary file 1). Some patients with thymoma did not respond at all to RTX, resulting unchanged or showing only a limited improvement7 14–16; others reported a significant improvement 7 9 11 12 15 16. However, the presence of thymoma has not been associated with a different response to RTX in AChR-MG 7 15 16…”

Section: Resultsmentioning

confidence: 99%

“…So, there could be a reporting bias toward successful treatment in AChR-MG, only because the use of RTX in this population is more frequent 9. Hence, several studies question the efficacy of RTX in AChR-MG, especially in comparison to MuSK-MG 14–16. There are only four prospective open-label studies which include a low number of patients 6 12 17 18.…”

Section: Discussionmentioning

confidence: 99%

“…Some authors also found a decrease in anti-AChR-Ab levels 1 2 11 16 17. However, in some cases, the reduction in antibody titres does not correlate with the clinical outcome,12 14 16 17 maybe because autoantibodies may accumulate at the neuromuscular junction 6. Another possible explanation is that RTX is responsible for the removal of B cells, rather than autoantibodies.…”

Section: Discussionmentioning

confidence: 99%

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Rituximab in AChR subtype of myasthenia gravis: systematic review

Stefano

Lupica

Rispoli

et al. 2020

J Neurol Neurosurg Psychiatry

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Myasthenia gravis (MG) is a chronic autoimmune disorder of the neuromuscular junction characterised by an autoantibody against acetylcholine receptor (AChR-Ab), autoantibody against muscle-specific kinase (MuSK-Ab), lipoprotein-related protein 4 or agrin in the postsynaptic membrane at the neuromuscular junction. Many patients are resistant to conventional treatment and effective therapies are needed. Rituximab (RTX) is a monoclonal antibody directed against CD20 antigen on B cells which has been successfully employed in anti-MuSK-Ab+MG, but the efficacy in anti-AChR-Ab+MG is still debated. The purpose of this systematic review was to describe the best evidence for RTX in the acetylcholine receptor subtype. The authors undertook a literature search during the period of 1999–2019 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analys methodology, employing (myasthenia)+(gravis)+(RTX) as search terms. The analysis was confined to studies that include at least five patients with confirmed anti-AChR-Ab+MG. Thirteen studies have been selected, showing a good safety. The data obtained were heterogeneous in terms of posology, administration scheme and patients’ evaluation, ranging from a minimum of two to a maximum of three cycles. RTX led to a sustained clinical improvement with prolonged time to relapse, in parallel to a reduction or discontinuation of other immunosuppressive therapies. Treatment with RTX appears to work in some but not all patients with anti-AChR-Ab+MG, but randomised controlled trials are needed. Future studies should take into account the subtype of MG and employ reliable measures of outcome and severity focusing on how to identify patients who may benefit from the treatment. Trial registration number: NCT02110706.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Rituximab in AChR subtype of myasthenia gravis: systematic review

Stefano

Lupica

Rispoli

et al. 2020

J Neurol Neurosurg Psychiatry

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“…Thus, rituximab-treated AChR-MG and MuSK-MG patients often have disease relapse or recurrence after an initial phase of disease remission (28). Nevertheless, some studies have reported the efficacy of rituximab for treatment of MG, particularly MuSK-MG (29,30). RTX was approved by USA FDA for treating refractory RA through intravenous infusion (31).…”

Section: Cd20-targeting Mabsmentioning

confidence: 99%

New Approaches to Targeting B Cells for Myasthenia Gravis Therapy

Huda

2020

Front. Immunol.

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Current therapies for myasthenia gravis (MG) are limited, and many investigations have recently focused on target-specific therapies. B cell-targeting monoclonal antibody (mAb) therapies for MG are increasingly attractive due to their specificity and efficacy. The targeted B cell biomarkers are mainly the cluster of differentiation (CD) proteins that mediate maturation, differentiation, or survival of pathogenic B cells. Additional B cell-directed therapies include non-specific peptide inhibitors that preferentially target specific B cell subsets. The primary goals of such therapies are to intercept autoantibodies and prevent the generation of an inflammatory response that contributes to the pathogenesis of MG. Treatment of patients with MG using B cell-directed mAbs, antibody fragments, or selective inhibitors have exhibited moderate to high efficacy in early studies, and some of these therapies appear to be highly promising for further drug development. Numerous other biologics targeting various B cell surface molecules have been approved for the treatment of other conditions or are either in clinical trials or preclinical development stages. These approaches remain to be tested in patients with MG or animal models of the disease. This review article provides an overview of B cell-targeted treatments for MG, including those already available and those still in preclinical and clinical development. We also discuss the potential benefits as well as the shortcomings of these approaches to development of new therapies for MG and future directions in the field.

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Comparison Between Rituximab Treatment for New-Onset Generalized Myasthenia Gravis and Refractory Generalized Myasthenia Gravis

et al. 2020

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IMPORTANCE Use of biologic agents in generalized myasthenia gravis is generally limited to therapy-refractory cases; benefit in new-onset disease is unknown. OBJECTIVE To assess rituximab in refractory and new-onset generalized myasthenia gravis and rituximab vs conventional immunotherapy in new-onset disease. DESIGN, SETTING, AND PARTICIPANTSA retrospective cohort study with prospectively collected data was conducted on a county-based community sample at

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High efficacy of rituximab for myasthenia gravis: a comprehensive nationwide study in Austria

Cited by 62 publications

References 29 publications

Rituximab in AChR subtype of myasthenia gravis: systematic review

Rituximab in AChR subtype of myasthenia gravis: systematic review

New Approaches to Targeting B Cells for Myasthenia Gravis Therapy

Comparison Between Rituximab Treatment for New-Onset Generalized Myasthenia Gravis and Refractory Generalized Myasthenia Gravis

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