What is the role of prednisone (corticosteroid) in treating Myasthenia Gravis (MG)?

Role of Prednisone in Myasthenia Gravis Treatment

Prednisone at 1-1.5 mg/kg orally daily is the cornerstone immunosuppressive therapy for myasthenia gravis patients with moderate to severe symptoms (Grade 2 or higher) who remain symptomatic despite optimal pyridostigmine dosing, with response rates of 66-85%. 1

Initial Treatment Algorithm

Mild Disease (Grade 2: Some ADL Interference)

• Start pyridostigmine first at 30 mg orally three times daily, titrating gradually to a maximum of 120 mg four times daily based on symptom response 2
• Approximately 50% of patients with mild disease respond adequately to pyridostigmine alone 1
• Add prednisone 1-1.5 mg/kg orally daily if symptoms persist despite optimal pyridostigmine dosing 2
• Wean corticosteroids gradually based on symptom improvement 2

Severe Disease (Grade 3-4: Limiting Self-Care, Dysphagia, Respiratory Weakness)

• Immediately initiate prednisone 1-1.5 mg/kg orally daily (or methylprednisolone 1-2 mg/kg/day IV) 2
• Simultaneously administer IVIG 2 g/kg over 5 days (0.4 g/kg/day) or plasmapheresis for 5 days 2
• Continue corticosteroids throughout acute treatment 2
• Admit to hospital with ICU-level monitoring capability 2

Critical Dosing Considerations

Starting Dose Strategy

• High-dose daily prednisone (1-1.5 mg/kg) is more effective than low-dose regimens for achieving disease control 3
• High-dose therapy carries increased risk of initial exacerbation (mild to moderate severity in most cases) compared to low-dose approaches 3
• Concurrent plasmapheresis with prednisone initiation prevents steroid-induced exacerbation in patients with bulbar or respiratory weakness 4, 5

Exacerbation Risk Factors

• Older age, generalized MG, bulbar symptoms, disease severity, presence of thymoma, and recent thymectomy increase risk of steroid-induced worsening 3
• Methylprednisolone causes fewer exacerbations than prednisone, which in turn causes fewer than cortisone 3
• Most exacerbations occur within 24-48 hours of initiation but are prevented by simultaneous plasmapheresis 5

Monitoring Requirements During Corticosteroid Therapy

Essential Assessments

• Pulmonary function testing with negative inspiratory force (NIF) and vital capacity (VC) at baseline and during treatment 2, 1
• Daily neurologic evaluation during acute treatment phases 2
• Frequent monitoring for respiratory compromise, especially in first 48 hours after steroid initiation 1

Concurrent Diagnostic Workup

• Acetylcholine receptor (AChR) and antistriated muscle antibodies 2
• If AChR negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 2
• Creatine phosphokinase (CPK), aldolase, ESR, and CRP to evaluate for concurrent myositis 2
• Electrodiagnostic studies including repetitive nerve stimulation and jitter studies 2

Critical Medication Avoidance

Immediately discontinue or avoid these medications that worsen myasthenic weakness:

• β-blockers 2, 1
• Intravenous magnesium 2, 1
• Fluoroquinolone antibiotics 2, 1
• Aminoglycoside antibiotics 2, 1
• Macrolide antibiotics 2, 1

Long-Term Corticosteroid Management

Steroid-Sparing Strategies

• Azathioprine, cyclosporine, and mycophenolate mofetil are increasingly used as first-line treatments and steroid-sparing agents 4
• IVIG should NOT be used for chronic maintenance therapy in myasthenia gravis 6
• IVIG is reserved exclusively for acute exacerbations or crisis situations requiring hospitalization 6

Tapering Protocol

• Taper corticosteroids gradually based on symptom improvement 2
• Maintain lowest effective dose to control symptoms while minimizing side effects 4
• ICPi-associated myasthenia gravis may be monophasic, potentially not requiring additional corticosteroid-sparing agents 2

Evidence Quality and Strength

The recommendations are primarily based on 2018 ASCO guidelines for immune-related adverse events 2 and 2025 American Academy of Neurology/American College of Neurology guidance 1, 6. While a 2005 Cochrane review found limited high-quality randomized controlled trial evidence for corticosteroids in MG 7, the short-term benefit compared to placebo supports decades of observational data and expert consensus. The 2021 systematic review provides the most recent evidence on exacerbation risks 3, while the 1998 study demonstrates the efficacy of combining plasmapheresis with high-dose prednisone to prevent steroid-induced worsening 5.