Myasthenia gravis (MG) is a relatively rare autoimmune disorder in which antibodies form against nicotinic acetylcholine (ACh) postsynaptic receptors at the neuromuscular junction (NMJ) of the skeletal muscles, causing muscle weakness and rapid muscle fatigue. It is a type-II hypersensitivity immune response.
The basic pathology is a reduction in the number of ACh receptors (AChRs) at the postsynaptic muscle membrane brought about by an acquired autoimmune reaction producing anti-AChR antibodies.The reduction in the number of AChRs results in a characteristic pattern of progressively reduced muscle strength with repeated use and recovery of muscle strength after a period of rest.
The ocular and bulbar muscles are affected most commonly and most severely, but most patients also develop some degree of fluctuating generalized weakness.
The overall incidence rate of myasthenia gravis (MG) has been estimated at 2.1 to 5.0 per million people per year and has not changed over time. However, the prevalence rate has increased since the 1950s in keeping with the declining mortality rate in MG as well as improved diagnostic precision.
Classically, the overall female-to-male ratio has been considered to be 3:2, with a female predominance in younger adults (ie, patients aged 20-30 years) and a slight male predominance in older adults (ie, patients older than 50 years). The mean age of onset is 28 years in females and 42 years in males.
MG is a well-understood and well-managed disease. Pharmacologic therapy includes anticholinesterase agents, such as pyridostigmine, and immunosuppressive agents, such as corticosteroids, azathioprine, mycophenolate mofetil, tacrolimus, sirolimus, cyclosporine, cyclophosphamide, rituximab, plasmapheresis, and intravenous immune globulin (IVIg).
Thymectomy has a significant role in the treatment of patients with generalized MG who are positive for acetylcholine receptor antibodies. Thymectomy becomes mandatory if a thymoma is present. Patients with MG require close follow-up care by a neurologist or neuromuscular specialist in cooperation with their primary care physician.
Rheumatoid arthritis drug effective against myasthenia
Early intervention with rituximab, a drug used in the treatment of rheumatoid arthritis (RA), can reduce the risk of deterioration in myasthenia gravis, an autoimmune disease that causes loss of muscle control. This is according to a randomised clinical study led by researchers at Karolinska Institutet in Sweden and published in the journal JAMA Neurology.
This study included 47 adult patients who had been diagnosed with myasthenia over the past year. Twenty-five of them were randomly assigned to a one-off treatment with 500 mg rituximab, a tried and tested drug used to treat rheumatoid arthritis, and 22 to a placebo group. The study was conducted at seven clinics in Sweden and the patients were followed for up to 48 weeks.
After four months, 71% of the rituximab group had attained good control of their disease according to a well-established 13-item rating scale, compared with 29% of the placebo group. Later follow-ups at six, nine and twelve months produced similar results.
The rituximab group also received on average lower doses of cortisone, and needed fewer adjuvant treatments. However, they also reported more adverse reactions, most of which were mild. One patient with previously diagnosed heart disease in the group died from a myocardial infarction with cardiac arrest. Three patients in the placebo group needed hospital care during the study period, two for life-threatening conditions related to a deterioration of their myasthenia.
With this result it is important to 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. Also it is necessary to find markers that can predict the course of the disease at an early stage.
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 Sundström, Oskar Wickberg, Susanna Brauner, Thomas Frisell, (September 19, 2022). Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis. JAMA Neurology. Retrieved from : https://jamanetwork.com/journals/jamaneurology/fullarticle/2796552