Rituximab, a monoclonal antibody therapy approved for treating rheumatoid arthritis and other autoimmune conditions, could be an effective first-line treatment for the autoimmune muscle condition myasthenia gravis according to a recent clinical study.
In the trial, researchers from the Karolinska Institute in Sweden tested rituximab in a group of 47 newly diagnosed patients with the autoimmune disease and found that after four months of therapy, 71% had good control of their disease.
Myasthenia gravis is a rare condition affecting up to 40 in 100,000 individuals in the U.S. The immune system of patients with the condition attacks receptors between nerves and muscles, which leads to muscle weakness and fatigue.
“While disease severity varies widely, it is well acknowledged that among those with generalized symptoms, many experience substantial morbidity and sometimes even life-threatening events,” explain the researchers in the paper describing the work published in JAMA Neurology.
Although biologic therapies such as rituximab have been used as third-line therapies for patients with myasthenia gravis, the first line option is normally oral corticosteroids followed by oral steroid-sparing immunosuppressive drugs such as azathioprine. When biologics are used, only the complement inhibitor eculizumab is officially approved for this use. Treatment comes with increased infection risk and it is prohibitively expensive for most patients.
In this study, Fredrik Piehl, a professor at the Department of Clinical Neuroscience, Karolinska Institute, and colleagues recruited the 47 newly diagnosed patients to take part in the randomized controlled trial. Of the participants, 25 were randomized to receive a single 500mg intravenous infusion of rituximab and 22 to receive a placebo.
The primary endpoint was the proportion of individuals with minimal disease manifestations with low doses of corticosteroids and no need of rescue treatment at four months. In the treatment group this was 71% versus 29% with placebo, a statistically significant difference.
“Patients with new onset myasthenia who received rituximab as a complement to standard of care showed greater improvement compared with patients who were given a placebo,” said Piehl, the study’s principal investigator, in a press statement.
“They also needed fewer adjuvant treatments and lower doses of cortisone than the placebo group. These are encouraging results that give hope for a more effective strategy for controlling new onset myasthenia more quickly, even if larger studies will be needed to assess the long-term effects of the treatment.”
Rituximab has been used ‘off-label’ for a number of conditions including multiple sclerosis (MS) and myasthenia gravis, but it is useful for medical professionals to have randomized placebo-controlled trials such as the current study to refer to.
“We’ll now, in a way similar to that with MS, analyze the long-term benefit-risk balance of the treatment with the help of national data collected via the Swedish myasthenia registry and national health registries. We also need to find markers that can predict the course of the disease at an early stage,” emphasized Piehl.