Rituximab treats myasthenia gravis patients with anti-MuSK antibodies
Therapy let patients reduce, stop other medicines, including corticosteroids
Rituximab effectively treated most myasthenia gravis (MG) patients who were positive for antibodies against muscle-specific tyrosine kinase (MuSK), a small study shows.
The therapy eased MG symptoms and led to gains in measures of clinical severity. It also enabled patients to reduce or stop taking other medications, including corticosteroids, and lowered self-reactive antibody levels.
“We suggest that [rituximab] might be considered an early therapeutic option, even as a first-line treatment to reduce the risk of disease worsening in anti-MuSK positive generalized MG,” the researchers wrote.
The study, “Clinical and laboratory remission with rituximab in anti-MuSK-positive myasthenia gravis”, was published in the Irish Journal of Medical Science.
In MG, self-reactive antibodies attack proteins needed for nerve-muscle communication, leading to muscle weakness and fatigue. While most patients have self-reactive antibodies that target the acetylcholine receptor (AChR), 5%-8% have antibodies that target the MuSK protein. Patients with anti-MuSK antibodies often fail to respond to common MG treatments, such as acetylcholinesterase inhibitors like Mestinon, and are more likely to rely on steroids.
An anti-MuSK antibody MG treatment?
Rituximab, which is sold under the name Rituxan and others, is an antibody-based treatment that targets and destroys B-cells, the immune cells that produce the self-reactive antibodies that drive MG. By reducing B-cells, rituximab may lower the levels of MG-causing antibodies, easing the symptoms of MG and its severity.
Rituximab isn’t officially approved for MG, but is sometimes used off-label to treat patients who don’t respond to standard treatments, including those with anti-MuSK antibodies.
To further evaluate rituximab’s effects in MG, researchers in Turkey analyzed data from 16 patients with generalized MG and anti-MuSK antibodies treated between January 2010 and September 2023. The patients were chosen for rituximab based on their poor clinical responses to other treatments, frequent or severe symptoms, or severe side effects from other treatments.
They received two infusions into the vein of 1,000 mg of rituximab two weeks apart as part of an induction regimen. Maintenance doses of 1,000 mg were then administered at intervals of three to six months, based on their clinical evaluation. Three-quarters of the patients were female.
The number of rituximab treatment cycles ranged from two to nine, with a mean of 4.7. The patients were followed for a mean of nearly five years after starting rituximab.
Effects of rituximab
Rituximab reduced disease severity for most patients. Thirteen (81.3%) achieved a status of minimal manifestations, which is no symptoms or functional limitations caused by MG, but with some degree of muscle weakness, or better at their last visit.
At that visit, 93% of patients had discontinued corticosteroids. The median time to taper and discontinue corticosteroids after rituximab treatment was 11 months. All those taking other oral immunosuppressants also stopped taking them.
Twelve of 15 patients (80%) tested negative for anti-MuSK antibodies after taking rituximab. Eleven of them achieved complete stable remission, which means no signs or symptoms of the disease for at least a year in the absence of specific MG treatment.
The “changes in antibody levels seemed associated with clinical outcomes,” wrote the researchers, who acknowledged they couldn’t statistically analyze which factors predicted a good outcome after rituximab treatment due to the small number of study patients. However, “[rituximab] may be better in controlling relapses and achieving remission when started earlier without the disease severely worsening,” they wrote.
The therapy was well tolerated overall, with no observable side effects.
“[Rituximab] is an effective treatment in anti-MuSK-positive MG,” wrote the researchers, who added that “prospective studies in larger cohorts, with predefined treatment regimens and certain sampling intervals, are warranted to elucidate the effect of [rituximab] treatment on anti-MuSK antibody levels and the association between disease course and antibody levels.”
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