What is the recommended acute and long‑term management for a patient with MOG‑IgG–positive demyelinating disease?

Management of MOG-IgG-Positive Demyelinating Disease

For acute attacks, treat with high-dose intravenous methylprednisolone followed by a prolonged oral corticosteroid taper; for severe or steroid-refractory cases, use plasma exchange or intravenous immunoglobulin (IVIG) as second-line therapy. 1

Acute Attack Management

First-Line Treatment

• High-dose IV methylprednisolone is the standard acute therapy with good treatment response rates 2, 3, 4
• Critical distinction from MS: MOG-EM carries a high risk of flare-ups after abrupt steroid cessation 1

Steroid Tapering Strategy

• Prolonged oral corticosteroid taper is essential after the acute phase 1, 3, 4
  • 71.4% of Swiss neurologists recommend oral steroid tapering in NMOSD, and 85.7% in MOGAD 5
  • A slow taper may lower relapse risk 3
  • This requires close monitoring and careful tapering to prevent early relapses 1

Second-Line Acute Therapies

When patients show inadequate response to methylprednisolone:

• Plasma exchange (PEX) or immunoadsorption (IA) 1
  • MOG-IgG-positive patients are particularly responsive to antibody-depleting treatments 1
• IVIG as an alternative, especially effective in children 1, 2, 4
• Early use of PEX or IVIG may be beneficial for severe attacks or corticosteroid-refractory cases 3, 6

Important caveat: Do not delay immunosuppressive therapy while awaiting MOG-IgG results, as laboratory processing can take 10+ days. Initiate treatment based on clinical and radiological suspicion 7.

Long-Term Preventative Management

Decision to Initiate Maintenance Therapy

The approach differs dramatically from NMOSD:

• In NMOSD: All participants advocate maintenance treatment after the first attack 5
• In MOGAD: Only 10% recommend treatment after the first attack 5

For MOGAD, consider maintenance therapy after the first attack only if:

• Severe attacks (38% of experts recommend) 5
• Persistent MOG-antibodies at 3-month follow-up (10% recommend) 5
• Both severe attacks AND persistent antibodies (19% recommend) 5

For relapsing disease: Initiate maintenance therapy after confirmed second attack 3, 4

Maintenance Therapy Options

First-Line: Rituximab

• Most commonly prescribed drug for both NMOSD and MOGAD 5, 2
• B cell-depleting therapy with good response, though patients may relapse immediately after B cell re-occurrence 1

Alternative Maintenance Therapies (in descending order of evidence):

1. IVIG - emerging as probably the most effective therapy for recurrent MOGAD 4

   • Monthly IVIG particularly effective in pediatric relapsing cases with low side effect profile 8
   • No further attacks reported in relapsing pediatric cases on monthly IVIG 8

2. Mycophenolate mofetil 2

3. Azathioprine 2

4. Chronic low-dose oral corticosteroids 2, 4

5. IL-6 receptor antagonists (tocilizumab, satralizumab) - emerging option for refractory cases 2, 3

   • Prospective trials underway 3
   • No major safety concerns with available therapies 2

6. Neonatal Fc receptor inhibitors (efgartigimod) - novel option 3, 9

   • First documented use as rescue therapy showed substantial functional recovery 9
   • Prospective trials in progress 3

Duration and De-escalation

Key difference from NMOSD:

• Tendency to recommend de-escalation or discontinuation in stable MOGAD patients, but NOT in NMOSD 5
• Monitor MOG-IgG serostatus: antibodies may disappear in monophasic disease (especially pediatric ADEM) 1
• Retest at 3 months and 6 months after first attack 8
  • Negative at 3 months suggests monophasic course 8
  • However, titers at 6 months can be inconsistent 8

Critical warning: If discontinuing treatment based on seronegativity, close monitoring of MOG-IgG serostatus is essential, as transient seroconversion can occur even in relapsing disease 1. The interval between first and second attack varies considerably—some patients relapse only after several years 1.

Common Pitfalls to Avoid

1. Do not use MS disease-modifying therapies: Some MS drugs may be ineffective or harmful in MOG-EM due to different immunopathogenesis 1

2. Do not abruptly stop steroids: High risk of early relapse requires careful tapering 1

3. Do not wait for disease activity before treatment change: This is an unwise approach given available safe therapies 2

4. Do not base long-term decisions solely on antibody disappearance: Titers can fluctuate with treatment and disease activity 1

5. Do not assume monophasic disease too early: Some patients relapse after years 1