Early intervention with rituximab, a drug used to treat rheumatoid arthritis (RA), can reduce the risk of worsening of myasthenia gravis, an autoimmune disease that causes loss of muscle control. This is according to a randomized clinical study led by researchers at Karolinska Institutet in Sweden and published in the journal Gamma Neurology.
Patients with myasthenia gravis who received rituximab as a supplement to standard of care showed greater improvement compared to patients who were given a placebo. They also needed fewer adjuvant therapies and lower doses of cortisone than the placebo group. These are encouraging results that give hope for a more effective strategy to control new-onset myasthenia gravis, even if larger studies are needed to evaluate the long-term effects of treatment.”
Frederic Bell, Professor in the Department of Clinical Neuroscience, Karolinska Institutet, and principal investigator on the study
In myasthenia gravis, the immune system attacks receptors between nerves and muscles, causing muscle weakness and fatigue. It often starts around the eye muscles but usually spreads to other muscles in the body. The disease tends to progress in flare-ups, and since there is no curative treatment, the intervention is primarily aimed at suppressing the immune system and treating symptoms. About 25 per 100,000 people live with the disease in Sweden, the majority of whom are women.
There is only one approved drug for myasthenia gravis, Soliris, but the treatment is expensive, which means that very few patients – none yet in Sweden – have benefited from it. Instead, many patients are treated with cortisone, which can cause side effects, and older tablet treatments tend to lack scientific support.
The current study included 47 adult patients diagnosed with myasthenia gravis within the past year. 25 of them were randomly assigned to a one-time treatment with 500 mg rituximab, a tried and tested drug used to treat rheumatoid arthritis, and 22 to the placebo group. The study was conducted in seven clinics in Sweden and patients were followed for up to 48 weeks.
After four months, 71 percent of the rituximab group achieved good disease control on a well-established 13-item rating scale, compared with 29 percent of the placebo group. Subsequent follow-up at six, nine, and twelve months yielded similar results.
The rituximab group also received, on average, lower doses of cortisone, and required fewer adjuvant treatments. However, they also reported more adverse reactions, most of which were mild. A patient with previously diagnosed heart disease in the group died of myocardial infarction with cardiac arrest. Three patients in the placebo group required hospital care during the study period, and two had life-threatening conditions associated with myasthenia gravis.
The researchers note that the study is relatively small with an imbalance in some key characteristics between the two groups, which is a limitation. At the same time, the results are promising and motivate further studies.
“The use of rituximab for myasthenia gravis increased in Sweden even before the results of the study were finalized,” says Fredrik Bell. “It is also a treatment familiar to neurologists in Sweden thanks to the fairly common and controversial description of multiple sclerosis (MS). Balance the risks and benefits over the term of treatment with the help of national data collected via the Swedish Myasthenia gravis and national health registries. We also need to find markers It can predict the course of the disease at an early stage.”
The study was funded by the Swedish Research Council. Some researchers received grants and fees from various drug companies, including some that market rituximab, outside the scope of this study.
Piehl, F., Auslander, N., and others. (2022) Efficacy and safety of rituximab in the treatment of newly-emerged generalized myasthenia gravis. RINOMAX randomized clinical trial. Gamma Neurology. doi.org/10.1001/jamaneurol.2022.2887.