Retrospective data suggest that high doses of rituximab are not needed to reach clinical remission in myasthenia gravis (MG), even with minimal doses of immunosuppressants, researchers said here at the 2021 virtual AAN Annual Meeting.
“In our experience, rituximab has a dramatic impact, reducing the number of hospitalizations for exacerbations, high-cost therapies," such as intravenous immunoglobulin and plasma exchange, “as well as the requirement of high doses of corticosteroids in the long-term with the consequences that this implies," said Juan Castiglione, MD, a resident in neurology at the Institute for Neurological Research (FLENI) at the University of Buenos Aires.
An independent expert said the results are encouraging but cautioned about the interpretation of retrospective data in a small series.
Researchers looked at 16 cases of refractory generalized MG from January 2015 to October 2020 that had a follow-up of at least two years. Eight of the patients had anti-muscle-specific-tyrosine kinase (MuSK) antibodies and eight had anti-acetylcholine receptor (AChR) antibodies.
Seven patients were treated with two doses of 500 mg of rituximab over two weeks; seven with two doses of 1,000 mg of rituximab over two weeks; and three with three doses of 500 mg of rituximab over three weeks. No patients had any detectable CD19- or CD20-positive B cell counts at six months or 12 months after rituximab treatment.
All patients achieved a score 2 or better on the Myasthenia Gravis Status and Treatment Intensity scale—meaning they had minimal clinical manifestations or pharmacologic remission either with low-dose oral therapy or prednisone monotherapy. The MuSK patients reached this score after a median of 46 days and the AChR patients after a median of 121.5 days, Dr. Castiglione said.
Rituximab treatment seemed to greatly reduce the need for immunosuppressive drugs. Among the AChR-related patients, five of the eight patients had been on high-dose dual therapy before rituximab, and three had been either high-dose monotherapy or low-dose dual therapy. After rituximab, six were on either high-dose monotherapy or low-dose dual therapy, and two required only symptomatic treatment.
Among the MuSK-related patients, six were on high-dose dual therapy, and two on either high-dose monotherapy or low-dose dual therapy before rituximab. After rituximab treatment, four of the eight were on either high-dose monotherapy or low-dose dual therapy; three were on low-dose monotherapy; and one required only symptomatic treatment.
Dr. Castiglione acknowledged that the AChR patients had a longer delay in treatment, and research has suggested that rituximab treatment is more effective in new-onset MG.
“Our study is one of the few that evaluated the response to rituximab at low doses, demonstrating that an efficacy similar to others published previously can be obtained despite having lower doses," he said. This represents a “paradigm shift" in low- and middle-income countries, he said.
“We believe that the quality of life of patients treated with rituximab improves significantly in the long term, not only due to the clinical stability achieved, but also due to the frank reduction in the daily dose of corticosteroids," he said.
Nicholas Silvestri, MD, FAAN, clinical associate professor of neurology at the Jacobs School of Medicine and Biomedical Sciences at the University of Buffalo, said the findings add to the evidence for rituximab's effectiveness in MG but cautioned against drawing firm conclusions from the data.
“The findings look promising, but then again so do many retrospective studies of rituximab in myasthenia," he said. “While the body of evidence is very clear that rituximab is a very effective treatment for MuSK myasthenia, the same is not true for AChR antibody-positive disease. Given that this study only included eight patients with AChR antibody-positive disease, I'm not completely convinced that rituximab is the best option to treat this form of the disease but it may be considered as a last resort in patients that have failed other available therapies."
The “major caution" with rituximab treatment is the risk of opportunistic infection due to the B cell depletion, with at least one case of progressive multifocal leukoencephalopathy reported following use of rituximab for MG treatment, he said.
Drs. Castiglione and Silvestri had no disclosures.
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AAN Abstract S12.001: Castiglione J, Barroso FA, Brand P, et al. Long-term remission with rituximab in refractory generalized myasthenia gravis.