Rheumatoid Arthritis Drug Effective Against Myasthenia

Newswise – Early intervention with rituximab, a drug used in the treatment of rheumatoid arthritis (RA), may reduce the risk of worsening myasthenia gravis, an autoimmune disease that causes loss of muscle control. This is according to a randomized clinical trial led by researchers at the Karolinska Institutet in Sweden and published in the journal JAMA Neurology.

“Patients with new myasthenia who received rituximab as an adjunct to standard treatment showed greater improvement compared to patients who received placebo,” said Fredrik Piehl, professor in the Department of Clinical Neuroscience, Karolinska Institutet, and principal investigator of the study. “They also required fewer adjuvant treatments and lower doses of cortisone than the placebo group. These are encouraging results that give hope for a more effective strategy to control new myasthenia more quickly, even if larger studies will be needed to assess the long-term effects of the treatment.”

In myasthenia gravis, the immune system attacks the receptors between nerves and muscles, causing abnormal muscle weakness and fatigue. It often starts around the eye muscles, but usually spreads to other muscles in the body. The disease usually progresses in flare-ups and since there is no curative treatment, the intervention is mainly aimed at weakening the immune system and treating the 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, Soliris, but the treatment is expensive, meaning very few patients – none so far in Sweden – have benefited from it. Instead, many patients are treated with cortisone, which can cause side effects, and older tablet treatments that often have no scientific backing.

The current study included 47 adult patients who had been diagnosed with myasthenia in the past year. Twenty-five of them were randomly assigned to a single treatment with 500 mg of rituximab, a proven drug for the treatment of rheumatoid arthritis, and 22 to a placebo group. The study was conducted in seven clinics in Sweden and the patients were followed for up to 48 weeks.

After four months, 71 percent of the rituximab group had achieved good control of their disease according to an established 13-item rating scale, compared to 29 percent of the placebo group. Subsequent follow-ups at 6, 9 and 12 months yielded similar results.

The rituximab group also received lower doses of cortisone on average and required fewer adjuvant treatments. However, they also reported more side effects, most of which were mild. One 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, two for life-threatening conditions associated with a worsening of their myasthenia.

The researchers note that the study is relatively small with an imbalance in some of the baseline characteristics between the two groups, which is a limitation. At the same time, the results are promising and motivate further research.

“The use of rituximab for myasthenia in Sweden increased even before the study results were final,” says Fredrik Piehl. “It is also a treatment that neurologists in Sweden are very well known for thanks to the widespread and somewhat controversial off-label prescribing of multiple sclerosis (MS). We will now, in a manner similar to that in MS, analyze the long-term benefit-risk balance of the treatment using national data collected through 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.”

The study was funded by the Swedish Research Council. Some researchers have received grants and awards from various pharmaceutical companies, including some that market rituximab, outside the scope of this study.

Publication: “Efficacy and Safety of Rituximab for New Emerging Generalized Myasthenia Gravis: The RINOMAX Randomized Clinical Trial.” Fredrik Piehl, Ann Eriksson-Dufva, Anna Budzianowska, Amalia Feresiadou, William Hansson, Max Albert Hietala, Irene Håkansson, Rune Johansson, Daniel Jons, Ivan Kmezic, Christopher Lindberg, Jonas Lindh, Fredrik Lundin, Ingela Nygren, Anna Rostedt Punga, Rayomand Press, Kristin Samuelsson, Peter Sundstrom, Oskar Wickberg, Susanna Brauner, Thomas Frisell. JAMA Neurologyonline Sep 19. 2022, doi: 10.1001/jamaneurol.2022.2887

Leave a Comment