By Michael Rubin, MD
Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Rubin reports no financial relationships relevant to this field of study.
SYNOPSIS: In uncontrolled, observational case series, rituximab treatment for myasthenia gravis appears to be effective and safe, but more studies are needed for confirmation.
SOURCE: Stieglbauer K, Pichler R, Topakian R. 10-year-outcomes after rituximab for myasthenia gravis: Efficacy, safety, costs of in-hospital care, and impact on childbearing potential. J Neurol Sci 2017;375:241-244.
Isolated case reports have noted the short-term benefit of rituximab (RTX) for myasthenia gravis (MG) refractory to standard immunotherapy, including corticosteroids, azathioprine, cyclosporine, plasmapheresis, and intravenous immunoglobulin. Long-term outcomes of rituximab on the other hand, including cost, safety, efficacy, and effect on childbearing potential, are less well documented, but are addressed in this paper.
Four patients with MG refractory to standard regimens, including prednisone, azathioprine, cyclosporine, mycophenolate mofetil, and plasmapheresis, were treated with RTX at a dose of 375 mg/m2 weekly for two weeks. Retreatment, a single infusion of 375 mg/m2, was based on B-cell counts using flow cytometry, but was spaced further apart when, in 2010, concern for potential complications, including progressive multifocal leukoencephalopathy, were raised. Thenceforth, RTX was given only after signs of clinical worsening developed.
Over a median follow-up of 10.1 years, regular neurological evaluations, including the Quantitative Myasthenia Gravis score, revealed dramatic improvement compared to pre-treatment scores, without the need for additional immunosuppressive medication. Three patients maintained their improvement since 2008, without the need for additional immunosuppression, while the fourth patient required only a single additional RTX infusion over a 6.7-year follow-up. Aside from occasional headaches in two patients, RTX was well-tolerated without severe infections or other adverse events noted. Two women each gave birth to a healthy child, one by vaginal delivery and one by caesarean delivery, after uncomplicated pregnancies, without MG flare. Cost of in-hospital MG patient care over the study period was decreased two- to 10-fold compared to pre-RTX cost, based on Austria’s diagnosis-related group system in which this retrospective study took place. RTX is safe and effective as treatment for refractory MG and, with further study, may emerge as a first-line choice.
COMMENTARY
Rituximab, a chimeric monoclonal antibody that depletes B-cells and their precursors, is a genetically engineered IgG1 kappa immunoglobulin produced by Chinese hamster ovary cells in medium containing gentamicin and purified by chromatography, comprising two heavy chains and two light chains, with a molecular weight of 145 kDa. Directed against CD20, the surface transmembrane phosphoprotein of B-lymphocytes, the Fab domain of RTX binds to CD20, while the Fc domain recruits immune effector cells for B-cell lysis, resulting in significant reductions, for up to six months, of circulating CD20+ B cells. Approved to treat a host of B-cell disorders, including rheumatoid arthritis, non-Hodgkin B-cell lymphoma, microangiopathic vasculitis, and granulomatosis with polyangiitis, RTX also appears efficacious in autoimmune disorders, such as autoimmune hemolytic anemia, immune thrombocytopenia, pemphigus, and MG that is refractory to standard immunomodulation therapy. In a review of 47 publications of RTX in MG, encompassing 28 single case reports with the remainder reporting two or more patients, totaling 30 childhood-onset and 137 adult-onset MG patients, RTX was well-tolerated and resulted in minimal manifestation disease (MG Foundation of America post-intervention scale) in 44% and pharmacologic/stable remission in 27% overall, with 72% of MuSK+ MG and 30% of AchR+ MG achieving minimal manifestation disease or better. Generally safe and effective, controlled trials hopefully will confirm its value in the neurologic arena.1
REFERENCE
- Tandan R, Hehir MK 2nd, Waheed W, Howard DB. Rituximab treatment of myasthenia gravis: A systematic review. Muscle Nerve 2017; Feb. 6. doi: 10.1002/mus.25597.
In uncontrolled, observational case series, rituximab treatment for myasthenia gravis appears to be effective and safe, but more studies are needed for confirmation.
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