What are the treatment options for myasthenia gravis?

Treatment Options for Myasthenia Gravis

Begin with pyridostigmine as first-line symptomatic therapy, then escalate systematically to corticosteroids for inadequate response, followed by steroid-sparing immunosuppressants for long-term management, while evaluating all AChR-positive patients for thymectomy. 1, 2

First-Line Symptomatic Treatment

Pyridostigmine is the initial treatment for all patients with myasthenia gravis, regardless of disease severity. 1, 3

• Start at 30 mg orally three times daily and gradually titrate upward based on symptom response 1, 2
• Maximum dose is 120 mg orally four times daily 1, 2
• Pyridostigmine is FDA-approved for myasthenia gravis treatment 3
• Approximately 50% of patients, particularly those with ocular manifestations, show minimal response to pyridostigmine alone and require escalation to immunosuppressive therapy 1, 2

Critical caveat: Pyridostigmine can cause bradycardia and high-degree AV block requiring treatment with muscarinic antagonists like hyoscyamine, which blocks cardiac side effects without reducing neuromuscular efficacy 4

Second-Line Immunosuppressive Therapy

Escalate to corticosteroids when pyridostigmine provides inadequate symptom control or for Grade 2 disease (mild generalized weakness interfering with activities of daily living). 1, 2

• Prednisone 0.5 mg/kg orally daily is the standard starting dose 2
• Corticosteroids demonstrate superior efficacy with 66-85% positive response rates compared to pyridostigmine's 50% response rate 1, 2
• Corticosteroids are the most consistently effective immunosuppressive agents but carry the highest incidence of potential side effects 1

Third-Line Steroid-Sparing Immunosuppressants

Add azathioprine for moderate to severe disease requiring long-term immunosuppression or when corticosteroid side effects are limiting. 1, 2

• Azathioprine is the most effective long-term immunosuppressive agent 5
• Mycophenolate is an alternative long-term option 5
• Calcineurin inhibitors (cyclosporine or tacrolimus) provide intermediate rates of improvement over months 5

Acute/Crisis Management

For Grade 3-4 disease (moderate to severe weakness) or myasthenic crisis, use IVIG or plasmapheresis for rapid symptom control. 2

• IVIG: 2 g/kg IV over 5 days (0.4 g/kg/day) 1, 2
• Plasmapheresis: 3-5 treatments 2
• These provide rapid improvement when necessary while waiting for slower-acting immunosuppressants to take effect 5

Surgical Intervention: Thymectomy

Evaluate all AChR-positive patients for thymectomy, which provides long-term symptom reduction. 1, 2

• Always perform thymectomy when thymoma is present (occurs in 10-20% of AChR-positive patients) 2
• Thymectomy is beneficial in AChR-positive generalized MG up to age 65 years 6
• Minimally invasive and robotic-assisted approaches have improved surgical outcomes 6

Novel Therapies for Refractory Disease

Consider efgartigimod alfa-fcab for AChR-positive patients who remain refractory to conventional immunosuppressive therapy. 2

• FDA-approved specifically for AChR-positive refractory myasthenia gravis 2
• Rituximab (B-cell inhibitor) is another option for refractory cases 5, 6

Critical Medication Avoidance

Immediately review and discontinue medications that worsen myasthenia gravis. 1, 2

• β-blockers 1, 2
• IV magnesium 1, 2
• Fluoroquinolones 1, 2
• Aminoglycosides 1, 2
• Macrolide antibiotics 1, 2

Essential Monitoring Requirements

Regular pulmonary function assessment is crucial in all patients with generalized myasthenia gravis to detect respiratory compromise early. 1, 2

• Monitor negative inspiratory force (NIF) and vital capacity (VC) 2
• Daily neurologic review and frequent pulmonary function testing for Grade 3-4 patients 2
• ICU-level monitoring may be necessary for rapidly progressive symptoms or respiratory muscle weakness 2
• 50-80% of patients with initial ocular symptoms develop generalized myasthenia within a few years, requiring vigilant monitoring for disease progression 1, 2

Treatment Algorithm by Disease Severity

Mild ocular or generalized MG (Grade 1):

• Pyridostigmine alone 1, 2
• Add corticosteroids if ocular motility abnormalities persist despite pyridostigmine 1

Moderate generalized MG (Grade 2):

• Pyridostigmine plus prednisone 0.5 mg/kg daily 2
• Consider azathioprine for steroid-sparing effect 1, 2

Severe generalized MG (Grade 3-4):

• IVIG or plasmapheresis for rapid control 2
• Corticosteroids plus azathioprine or other steroid-sparing agent 1, 2
• Evaluate for thymectomy 2

Refractory MG:

• Rituximab or efgartigimod alfa-fcab 2, 5

Special Considerations for Ocular Myasthenia

Early corticosteroid treatment is warranted when ocular motility abnormalities persist despite pyridostigmine, as ocular symptoms are highly variable and not readily remedied with prisms. 1, 7

• Ice pack application over closed eyes for 2-5 minutes may temporarily reduce symptoms and aid diagnosis 1, 2, 7
• Strabismus surgery should only be considered after disease stabilization, typically requiring 2-3 years of medical treatment 1, 2, 7
• Management requires collaboration between an experienced ophthalmologist and neurologist 1, 7