Medication in Patients with Myasthenia Gravis – What to Watch Out For?
According to current recommendations, the treatment of myasthenia gravis (MG) should be individualized, considering the severity of the disease, the type of autoantibodies, thymus pathology, and, last but not least, the patient's preferences and comorbidities. What are the usual treatment modalities? What specifics need to be considered when treating comorbidities or acute illnesses in patients with MG? The following text briefly summarizes the answers to these questions.
Myasthenia gravis – At the Junction of Nerve and Muscle
MG is a rare chronic autoimmune disease characterized by dysfunction and damage to the neuromuscular junction caused by pathological autoantibodies and complement. The prevalence in European countries is estimated by epidemiological studies to be 11–39 cases per 100,000 people.1
Common Treatment
Although the pathogenesis of MG is well-studied and the pathological autoantibodies causing the disease have been described, current treatment does not directly target them. According to current recommendations2, 3, the basis of therapy includes the following modalities:
1. Symptomatic treatment with acetylcholinesterase inhibitors (AChEI) – pyridostigmine should be the treatment of choice for most patients.2
2. Disease-modifying treatment:
- Systemic corticosteroid therapy – for patients who do not achieve remission with pyridostigmine.
- Immunosuppressive therapy – first-line azathioprine, 2 if ineffective or intolerant, cyclosporine, methotrexate,3 mycophenolate mofetil, or tacrolimus.
- Thymectomy – should be considered early in young patients with generalized MG and antibodies against the acetylcholine receptor (AChR), especially if they do not respond to immunosuppressive therapy.3
3. Escalation of treatment in cases of myasthenic crisis or refractory disease:
- Intravenous immunoglobulins (IVIG) and exchange plasmapheresis (PLEX) – used as short-term treatment in life-threatening symptoms.2
- Rituximab – should be considered as early therapy in patients with muscle-specific kinase (MuSK) antibodies who do not respond to immunosuppressive treatment.3
- Eculizumab – for severe refractory generalized MG with positive AChR antibodies.3
- Cyclophosphamide – in exceptional cases.
Other Medications and Their Impact on MG Symptoms
It is known that some medications can worsen muscle weakness in patients with MG. The most risky from this perspective include anesthetics, antibiotics, some psychiatric drugs, statins, beta-blockers, calcium channel blockers, and immune checkpoint inhibitors.4
Worsening of MG symptoms can be caused by several mechanisms. Some drugs (magnesium, botulinum toxin, antibiotics, or anesthetics) directly interfere with neuromuscular transmission, while others (benzodiazepines) can accentuate muscle weakness and fatigue indirectly. Attention should be paid to the risk of respiratory center depression, for example with opioids. Some drugs can trigger autoimmune MG – penicillamine, immune checkpoint inhibitors, interferon-alpha, tyrosine kinase inhibitors, statins, alemtuzumab, or chloroquine.4
Caution is also needed regarding potential interactions with administered AChEI and their side effects. AChEI as parasympathomimetics can cause bronchoconstriction. Suitable rescue medications are inhaled β2-sympathomimetics (e.g., fenoterol) and inhaled parasympatholytics (e.g., ipratropium). Conversely, some antispasmodics and anticholinergics (atropine, butylscopolamine) inhibit the cholinergic effects of AChEI.4
Conclusion
When prescribing medications to patients with MG, the individual risk-benefit ratio should always be considered.3 A detailed overview of contraindicated drugs in patients with MG and their possible alternatives has been prepared by experts from the Center for Diagnosis and Treatment of Myasthenia Gravis at the Department of Neurology, First Faculty of Medicine, Charles University, and General University Hospital in Prague. The latest version, updated in 2022, can be downloaded here.
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Sources:
1. Mevius A., Jöres L., Biskup J. et al. Epidemiology and treatment of myasthenia gravis: a retrospective study using a large insurance claims dataset in Germany. Neuromuscul Disord 2023; 33 (4): 324–333, doi: 10.1016/j.nmd.2023.02.002.
2. Sanders D. B., Wolfe G. I., Benatar M. et al. International consensus guidance for management of myasthenia gravis: executive summary. Neurology 2016; 87 (4): 419–425, doi: 10.1212/WNL.0000000000002790.
3. Narayanaswami P., Sanders D. B., Wolfe G. et al. International consensus guidance for management of myasthenia gravis: 2020 update. Neurology 2021; 96 (3): 114–122, doi: 10.1212/WNL.0000000000011124.
4. Týblová M. et al. Risky drugs in the diagnosis of myasthenia gravis. Center for Diagnosis and Treatment of Myasthenia Gravis, Neurology Clinic, First Faculty of Medicine, Charles University, and General University Hospital in Prague, 2022. Available at: www.mygra.cz/upload/docs/rizikova-leciva-u-dg-mg.pdf
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