What is the treatment for myasthenia gravis?

Treatment of Myasthenia Gravis

Start pyridostigmine bromide 30 mg orally three times daily as first-line treatment, gradually increasing to a maximum of 120 mg four times daily based on symptom response. 1, 2, 3

Stepwise Treatment Algorithm

First-Line: Acetylcholinesterase Inhibitors

• Pyridostigmine is FDA-approved and the initial treatment for all myasthenia gravis patients, providing symptomatic relief by enhancing neuromuscular transmission 3, 4
• Titrate from 30 mg three times daily up to 120 mg four times daily as tolerated 1, 2
• Important caveat: Approximately 50% of patients with ocular myasthenia show minimal response to pyridostigmine alone, necessitating escalation to immunosuppressive therapy 5, 4

Second-Line: Corticosteroids

• Add prednisone 0.5 mg/kg orally daily when pyridostigmine provides inadequate symptom control or for Grade 2 or higher disease (symptoms interfering with activities of daily living) 1, 2
• Corticosteroids demonstrate superior efficacy with 66-85% positive response rates compared to pyridostigmine's 50% response rate 5, 4, 1
• Corticosteroids are the most consistently effective immunosuppressive agents but carry the highest incidence of potential side effects 6

Third-Line: Steroid-Sparing Immunosuppressants

• Azathioprine is the primary steroid-sparing agent for moderate to severe disease or when corticosteroid side effects are problematic 1, 2, 7
• Alternative agents include mycophenolate mofetil, cyclosporine (limited by renal toxicity and hypertension), or cyclophosphamide for refractory cases 7, 6, 8

Acute/Crisis Management

• For Grade 3-4 disease (moderate to severe weakness) or myasthenic crisis: IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) or plasmapheresis for 3-5 days 1, 2
• Both IVIG and plasmapheresis show comparable efficacy for acute exacerbations 6
• ICU-level monitoring with frequent pulmonary function testing (negative inspiratory force and vital capacity) is mandatory for rapidly progressive symptoms 2

Surgical Intervention: Thymectomy

• Perform thymectomy in all patients with thymoma (occurs in 10-20% of AChR-positive patients) 2, 7
• Thymectomy is beneficial for AChR-positive generalized myasthenia gravis patients up to age 65 years, ideally within the first 6-12 months of disease 6, 9, 10
• Minimally invasive and robotic-assisted techniques have improved surgical outcomes 9

Refractory Disease Options

• For treatment-refractory myasthenia: Consider rituximab, high-dose cyclophosphamide, or eculizumab (FDA-approved complement inhibitor) 8, 10
• Efgartigimod alfa-fcab represents a newer targeted therapy for refractory cases 4

Critical Medication Avoidance

Immediately discontinue medications that exacerbate myasthenia gravis: 1, 2

• β-blockers
• IV magnesium
• Fluoroquinolones
• Aminoglycosides
• Macrolide antibiotics

Essential Monitoring Requirements

• Regular pulmonary function assessment is mandatory, as 50-80% of patients with initial ocular symptoms develop generalized myasthenia within a few years 1, 2
• Obtain CT chest with contrast after diagnosis to evaluate for thymoma 2
• Monitor for respiratory compromise with serial negative inspiratory force and vital capacity measurements 2

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 5, 9
• Ice pack test (apply over closed eyes for 2-5 minutes) can temporarily reduce misalignment and serves as a diagnostic tool 4, 1
• Strabismus surgery may be considered only after disease stabilization, typically requiring 2-3 years of medical treatment 5, 4

Multidisciplinary Management

Diagnosis and management requires collaboration between an experienced ophthalmologist and neurologist, with potential involvement of cardiothoracic surgery for thymectomy 5, 1, 2