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Abstract

Myasthenia gravis is a chronic autoimmune disease of the neuromuscular junction in which antibodies produced by the immune system target various components of the postsynaptic membrane and impair neuromuscular transmission, causing weakness and fatigue of skeletal muscle. Approximately 80% of patients with myasthenia gravis have antibodies against acetylcholine receptors (AChRs). The remaining 20% of patients typically have antibodies against muscle-specific tyrosine kinase (MuSK), antibodies against related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4), or are seronegative (i.e., do not have any detectable antibodies associated with myasthenia gravis). This condition can be localized to specific muscle groups (e.g., extrinsic ocular muscles) or it can be generalized, affecting many regions of the body. Myasthenia gravis may become life-threatening when it involves the bulbar or respiratory muscles, resulting in respiratory failure that requires intubation and mechanical ventilation (known as a ). Sex and age are important factors that appear to influence the occurrence of myasthenia gravis. In patients younger than 40 years, females have disproportionately high rates of myasthenia gravis. Conversely, in populations older than 50 years, myasthenia gravis is more common in males. Between the ages of 40 years and 50 years, and in adolescent populations, myasthenia gravis affects male and females approximately equally. In Ontario, myasthenia gravis has been estimated to have a crude prevalence rate of approximately 32.0 per 100,000 population, a number which has been increasing over time. Conventional therapies for the treatment of myasthenia gravis include cholinesterase inhibitors (e.g., pyridostigmine), which increase the amount of acetylcholine available at the neuromuscular junction, corticosteroids (e.g., prednisone), which are immunosuppressants, thymectomy, where the thymus gland is removed to stop the production of autoantibodies, and other immunomodulatory therapies (e.g., azathioprine, cyclosporine, IV immunoglobulin, and plasma exchange). The goal of these therapies is to achieve stable disease where patients experience limited symptoms (i.e., minimal manifestation status). Although many patients experience success with these approaches, approximately 10% of those with generalized myasthenia gravis are refractory to or are unable to tolerate conventional therapies. In these cases, individualized treatment strategies involving other immunomodulatory therapies, such as eculizumab or rituximab, may be considered. In October 2020, the CADTH Canadian Drug Expert Committee assessed the use of eculizumab for the treatment of adult patients with refractory generalized myasthenia gravis and gave a conditional recommendation in favour of reimbursement. However, the place of rituximab therapy in the treatment pathway for patients with refractory myasthenia gravis is unclear, and an assessment of the available literature could help inform clinicians and decision-makers on its appropriate use. The objective of this report is to review the clinical effectiveness and cost-effectiveness of rituximab therapy for the treatment of myasthenia gravis in those who are refractory to standard therapy. Additionally, this report aims to summarize the evidence-based guidelines regarding the use of rituximab for the treatment of myasthenia gravis. This report updates a 2018 CADTH report that concluded that rituximab therapy was associated with improvement in patients with myasthenia gravis; however, definitive conclusions were not possible at that time due to limitations of the clinical literature.

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