What is the initial treatment for myasthenia gravis?

Initial Treatment for Myasthenia Gravis

Pyridostigmine bromide administered orally is the first-line treatment for myasthenia gravis, starting at 30 mg three times a day and gradually increasing to a maximum of 120 mg four times a day as tolerated and based on symptoms. 1, 2, 3

First-Line Treatment: Acetylcholinesterase Inhibitors

• Pyridostigmine is FDA-approved for the treatment of myasthenia gravis and serves as the initial symptomatic treatment 3
• Typical starting dose is 30 mg orally three times a day, with gradual increases to a maximum of 120 mg four times a day as tolerated 1
• Pyridostigmine provides symptomatic relief by inhibiting acetylcholinesterase, thereby increasing acetylcholine availability at the neuromuscular junction 4
• While effective for symptom management, approximately half of patients with ocular symptoms may show minimal response 2

Second-Line Treatment: Corticosteroids

• If symptoms persist despite optimal pyridostigmine therapy, corticosteroids should be added 1, 2
• Prednisone is typically started at 1-1.5 mg/kg orally daily for generalized symptoms 1
• About 66-85% of patients show positive response to corticosteroids 2
• Corticosteroid dosing should be weaned based on symptom improvement 1

Treatment Based on Disease Severity

Mild Disease (MGFA Class 1-2)

• Begin with pyridostigmine for symptomatic relief 1, 2
• Add corticosteroids if symptoms interfere with activities of daily living 1
• Avoid medications that can worsen myasthenia: β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides 1

Moderate to Severe Disease (MGFA Class 3-4)

• Higher doses of corticosteroids are typically required 1
• Consider adding immunosuppressive therapy such as azathioprine or mycophenolate mofetil as steroid-sparing agents 5, 6
• For rapid improvement, intravenous immunoglobulin (IVIG) 2 g/kg over 5 days or plasmapheresis for 5 days may be necessary 1

Crisis (MGFA Class 5)

• Hospitalization with possible ICU-level monitoring is required 1
• IVIG or plasmapheresis should be initiated promptly 1, 7
• Frequent pulmonary function assessment and daily neurologic review are essential 1
• Pyridostigmine may be temporarily discontinued during crisis and restarted prior to extubation 7

Additional Treatment Considerations

• Thymectomy should be considered in patients with thymoma and may be beneficial in certain subpopulations 2, 6
• For refractory cases, medications such as rituximab, high-dose cyclophosphamide, or newer agents like efgartigimod alfa-fcab may be considered 8, 5
• Regular monitoring for disease progression is crucial, especially for respiratory symptoms 1, 2

Diagnostic Workup to Guide Treatment

• Confirm diagnosis with anti-acetylcholine receptor antibody testing (positive in approximately 80% of generalized MG cases) 6
• Consider testing for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies in seronegative cases 1
• Electrodiagnostic studies including repetitive nerve stimulation and single fiber electromyography can help confirm the diagnosis 1
• The Ice Test (application of ice pack over closed eyes) may demonstrate temporary improvement in ocular symptoms 1

Common Pitfalls to Avoid

• Failing to adjust pyridostigmine dosage gradually based on symptoms and tolerability 1, 4
• Not recognizing that acetylcholinesterase inhibitors provide only partial benefit and most patients eventually require immunosuppressive therapy 4
• Overlooking potential respiratory compromise, which requires immediate intervention 1
• Delaying initiation of second-line therapy when symptoms are inadequately controlled with pyridostigmine alone 2, 6