Rituximab for myasthenia gravis Three case reports and review of the literature
Department of Neurology, Academic Teaching Hospital Wagner-Jauregg, Linz, Austria. Journal of the neurological sciences
(Impact Factor: 2.47).
06/2009; 280(1-2):120-2. DOI: 10.1016/j.jns.2009.02.357
In generalized myasthenia gravis (MG), a wide array of immunosuppressive and immunomodulating treatments is being used in clinical practice, but most drugs lack evidence from randomized controlled trials supporting their use. Furthermore, many patients develop serious side effects or do not respond sufficiently to these drugs. We report three patients with generalized MG who were treated with rituximab, a monoclonal antibody against CD20+ cells that causes prolonged B cell depletion. In all three patients, treatment with rituximab led to a sustained clinical improvement and discontinuation or reduction of prednisolone and other drugs. Rituximab was well tolerated. Therapy with rituximab was guided by the total count of peripheral B lymphocytes. Reviewing the anecdotal literature on rituximab for MG, we conclude that preliminary data on the efficacy and safety of rituximab are encouraging and that further studies in MG seem warranted.
Available from: Renato Mantegazza
- "Small series of patients are available, and both MG with and without thymoma have been treated. Rituximab provides promising expectations for the treatment of MG,67–70 although no RCTs have been conducted so far. "
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ABSTRACT: Myasthenia gravis (MG) is an autoimmmune disease in which autoantibodies to different antigens of the neuromuscular junction cause the typical weakness and fatigability. Treatment includes anticholinesterase drugs, immunosuppression, immunomodulation, and thymectomy. The autoimmune response is maintained under control by corticosteroids frequently associated with immunosuppressive drugs, with improvement in the majority of patients. In case of acute exacerbations with bulbar symptoms or repeated relapses, modulation of autoantibody activity by plasmapheresis or intravenous immunoglobulins provides rapid improvement. Recently, techniques removing only circulating immunoglobulins have been developed for the chronic management of treatment-resistant patients. The rationale for thymectomy relies on the central role of the thymus. Despite the lack of controlled studies, thymectomy is recommended as an option to improve the clinical outcome or promote complete remission. New videothoracoscopic techniques have been developed to offer the maximal surgical approach with the minimal invasiveness and hence patient tolerability. The use of biological drugs such as anti-CD20 antibodies is still limited but promising. Studies performed in the animal model of MG demonstrated that several more selective or antigen-specific approaches, ranging from mucosal tolerization to inhibition of complement activity or cellular therapy, might be feasible. Investigation of the transfer of these therapeutic approaches to the human disease will be the challenge for the future.
Neuropsychiatric Disease and Treatment 03/2011; 7(1):151-60. DOI:10.2147/NDT.S8915 · 1.74 Impact Factor
Available from: ncbi.nlm.nih.gov
- "Therefore, natalizumab blocking VLA-4 interaction with VCAM-1 or fibronectin prevents infiltration of lymphocytes during inflammation (Rice et al. 2005). Rituximab (Rituxan ® , IDEC Pharmaceuticals) is a chimeric mouse–human monoclonal antibody directed against CD20, which is expressed on B cells (Grillo-Lopez et al. 2000) and is used for the treatment of non-Hodgkin lymphomas (Fanale and Younes 2007), rheumatoid arthritis (Schuna 2007), autoimmune hematological disorders including autoimmune hemolytic anemia, acquired hemophilia, thrombotic thrombocytopenic and purpura (Garvey 2008), SLE (Ramos-Casals et al. 2009), myasthenia gravis (Stieglbauer et al. 2009), and MS (Cree et al. 2005; Wingerchuk and Weinshenker 2005; Bar-Or et al. 2008; Hauser et al. 2008; Linker et al. 2008). Binding of rituximab to CD20 on B cells results in their lysis and subsequent depletion of the B cell population in peripheral blood and CSF (Maloney et al. 1997; Monson et al. 2005). "
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ABSTRACT: Progressive multifocal leukoencephalopathy (PML) is a growing concern for patients undergoing immune modulatory therapies for treatment of autoimmune diseases such as multiple sclerosis. Currently, there are no drugs approved for the treatment of PML that have been demonstrated in the patient to effectively and reproducibly alter the course of disease progression. The human polyoma virus JC is the causative agent of PML. JC virus (JCV) dissemination is tightly controlled by regulation of viral gene expression from the promoter by cellular transcription factors expressed in cells permissive for infection. JCV infection likely occurs during childhood, and latent virus containing PML-associated promoter sequences is maintained in lymphoid cells within the bone marrow. Because development of PML is tightly linked to suppression and or modulation of the immune system as in development of hematological malignancies, AIDS, and monoclonal antibody treatments, further scrutiny of the course of JCV infection in immune cells will be essential to our understanding of development of PML and identification of new therapeutic targets.
Journal of Neuroimmune Pharmacology 09/2010; 5(3):404-17. DOI:10.1007/s11481-010-9203-1 · 4.11 Impact Factor
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ABSTRACT: Myasthenia gravis (MG) is an autoimmune disease that affects the post-synaptic area of the neuromuscular junction. Its hallmark is weakness that worsens with activity. MG incidence is rising in the recent decades, mostly the late onset subtype, which is considered to be due to the aging population or unknown environmental factors. The disease has several subtypes which defer slightly in the clinical characteristics, immunological markers, population distribution and the suitable treatments. The autoimmune nature of the disease is manifested by a decrease in the number of acetylcholine receptors in the muscle receptors which makes the endplate potential to be lower than the threshold needed to activate muscle fiber action potential. In our review we try to find the environmental influence on the disease.
Autoimmunity reviews 11/2009; 9(5):A383-6. DOI:10.1016/j.autrev.2009.11.011 · 7.93 Impact Factor
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