What is the management approach for Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD)?

Management of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD)

MOGAD requires aggressive acute treatment with high-dose intravenous corticosteroids followed by prolonged oral steroid tapering, and for relapsing disease, intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) appears to be the most effective long-term preventive therapy. 1, 2

Acute Attack Management

First-Line Acute Treatment

• Administer high-dose intravenous methylprednisolone (IVMP) as the primary acute treatment for all MOGAD attacks 1, 3
• IVMP was used in 85% of attacks in clinical practice with good outcomes 3
• For severe or refractory cases, add intravenous immunoglobulin (IVIG) to IVMP 3

Critical Post-Acute Phase Management

• Implement a prolonged oral corticosteroid taper after the acute attack to prevent rapid relapse, as MOGAD patients have a high risk of flare-ups after cessation of steroid treatment 4, 1
• This extended taper is a distinguishing feature of MOGAD management compared to other demyelinating diseases 4
• Close monitoring during steroid tapering is essential, as steroid-dependent symptoms are common 4

Rescue Therapies for Steroid-Refractory Cases

• Consider plasma exchange or immunoadsorption for patients who fail to respond adequately to IVMP, as MOG-IgG-positive patients may be particularly responsive to antibody-depleting treatments 4

Long-Term Disease-Modifying Therapy

Identifying Patients Who Need Maintenance Therapy

Predictors of relapsing disease course requiring long-term immunotherapy include: 2

• CSF pleocytosis >150 cells/mm³ (HR 3.3)
• Pediatric disease onset at age <9 years (HR 2.69)
• Initial presentation with meningoencephalitis (HR 3.42)
• Note that 64.6% of MOGAD patients develop a relapsing course, with 68.6% experiencing their first relapse within the first year, though relapses can occur 5-15 years after initial presentation 2

First-Line Maintenance Therapy

Scheduled immunoglobulin therapy (IVIG or SCIG) is the most effective steroid-sparing treatment for relapse prevention: 1, 2, 5

• In comparative studies, 78.6% of patients remained relapse-free on scheduled immunoglobulins versus 54.2% on rituximab and 50% on mycophenolate mofetil 2
• Patients treated with immunoglobulins had significantly fewer relapses compared to other immunotherapies (HR 0.1, p=0.014) 2
• Subcutaneous immunoglobulin (SCIG) offers advantages over IVIG including self-administration and fewer systemic adverse effects, with six reported patients showing good tolerability and no relapses during follow-up 5

Alternative Maintenance Options

When immunoglobulin therapy is not feasible, consider: 2, 3

• Rituximab (B-cell depleting therapy): 54.2% remained relapse-free 2
• Mycophenolate mofetil: 50% remained relapse-free 2, 3
• Chronic low-dose oral corticosteroids (prednisone): used in some patients but less data on efficacy 3

Therapies to AVOID

Do NOT use interferon-beta or natalizumab in MOGAD patients, as these MS-approved therapies may be ineffective or even harmful, with clear increases in relapse rate documented 4

Diagnostic Confirmation Requirements

Before initiating long-term therapy, ensure proper diagnosis: 4

• MOG-IgG seropositivity detected by cell-based assay using full-length human MOG as target antigen
• MRI or electrophysiological findings compatible with CNS demyelination
• Clinical syndrome of acute optic neuritis, myelitis, brainstem encephalitis, encephalitis, or combinations thereof

Monitoring Strategy

Short-Term Monitoring

• Re-test MOG-IgG at 6-12 months after initial attack, as antibody disappearance may indicate monophasic disease, though this is more common in pediatric ADEM cases 4
• Be aware that transient seronegativity can occur after treatment with steroids, plasma exchange, or immunosuppressants, so confirm persistent seronegativity before discontinuing long-term therapy 4

Long-Term Follow-Up

• Median time to first relapse is 9.5 months (range 2-120 months), requiring vigilant long-term monitoring even in apparently stable patients 3
• The median Expanded Disability Status Scale score improves from 3.5 at nadir to 0 at long-term follow-up, indicating generally benign long-term outcomes with appropriate treatment 3

Common Pitfalls to Avoid

• Do not misdiagnose MOGAD as multiple sclerosis: 33% of adult MOGAD patients meet McDonald criteria for MS at some point, leading to inappropriate use of MS therapies that may worsen outcomes 4
• Do not abruptly discontinue corticosteroids after acute treatment: this leads to frequent flare-ups and steroid-dependent symptoms 4
• Do not assume monophasic disease too early: first relapses can occur over a decade after initial presentation in 19.6% of relapsing patients 2