What are the guidelines for using Rituximab (rituximab) in neurology?

Rituximab Guidelines in Neurology

Rituximab is recommended as a first-line therapy for several neurological conditions, with specific protocols based on the disease type, severity, and patient characteristics. 1

Key Indications for Rituximab in Neurological Disorders

• Primary Central Nervous System Lymphoma (PCNSL): Rituximab is a component of the MATRix regimen (high-dose methotrexate, high-dose cytarabine, rituximab, thiotepa), which is recommended for eligible patients aged ≤65 years with ECOG PS 0-3 or aged ≤70 years with ECOG PS ≤2 1

• Neuromyelitis Optica Spectrum Disorders (NMOSD): Rituximab is widely used as an off-label treatment with evidence showing reduction in relapse frequency and neurological disability 2

• Multiple Sclerosis (MS): Used off-label as both first-choice and switching therapy, with evidence suggesting effectiveness in reducing relapses compared to interferon beta, glatiramer acetate, and dimethyl fumarate 3

• ANCA-Associated Vasculitis: Conditionally recommended over cyclophosphamide for remission induction in active, severe granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) 1

• Waldenström Macroglobulinemia (WM)-related neuropathy: Recommended for patients with moderate to severe IgM-related neuropathy, particularly when rapid improvement is needed 1

• Sjögren's Syndrome-related neuropathy: Effective through B-cell depletion, which reduces pathogenic autoantibodies and inflammatory mediators causing nerve damage 4

Dosing Protocols by Condition

• PCNSL: As part of MATRix regimen, though specific rituximab dosing is not standardized across all protocols 1

• NMOSD: 375 mg/m² weekly for 4 weeks, with maintenance doses determined by B-cell monitoring 5, 2

• MS: 375 mg/m² weekly for 4 weeks (FDA-approved dosing) or 1,000 mg on days 1 and 15 3

• ANCA-Associated Vasculitis: 375 mg/m² weekly for 4 weeks for remission induction 1, 6

• WM-related neuropathy: 375 mg/m² weekly for 4 weeks, with monitoring for IgM flare 1

• Multifocal Acquired Demyelinating Sensory and Motor (MADSAM) Neuropathy: Considered for severe refractory cases after failure of first-line therapies (IVIg, corticosteroids) 7

Special Considerations and Precautions

• IgM Flare: Transient increases in IgM levels occur in 40-50% of WM patients after rituximab initiation, which may worsen hyperviscosity, neuropathy, and cryoglobulinemia 1

• Prophylactic Plasmapheresis: Consider before rituximab in patients with high IgM levels (≥4,000 mg/dL) to minimize symptomatic IgM flare 1, 4

• Hepatitis B Reactivation: Prophylactic antiviral therapy is strongly recommended for patients who are hepatitis B core antibody positive before initiating rituximab 1

• Hypogammaglobulinemia: In the setting of persistent hypogammaglobulinemia without infection, continuation of rituximab therapy is conditionally recommended over switching to a different biologic DMARD 1

• Lymphoproliferative Disorders: Rituximab is conditionally recommended over other DMARDs for patients with previous lymphoproliferative disorder for which rituximab is an approved treatment 1

• Infusion Reactions: Common adverse effect, occurring in approximately 10% of patients 8, 2

• Infections: Observed in approximately 9% of patients, with most recovering completely 8, 2

Monitoring Recommendations

• B-cell Counts: Monitor CD19+ B-cell levels to guide retreatment decisions 9

• Immunoglobulin Levels: Regular monitoring of IgG, IgM, and IgA levels, particularly with prolonged treatment 9

• Neurological Assessment: For neuropathy indications, response should be assessed after 2-4 weeks using standardized neurological examinations 4

• Hepatitis B Monitoring: For patients with positive hepatitis B serology, monitor viral load regularly 1

• Infection Surveillance: Regular clinical assessment for signs of infection, particularly in patients receiving concomitant immunosuppression 2

Common Pitfalls and Management Strategies

• IgM Flare Management: For WM patients experiencing symptomatic flare, plasmapheresis may be required; consider bortezomib before rituximab to rapidly reduce IgM levels 1

• Symptomatic Treatment of Neuropathy: Consider gabapentin, pregabalin, or duloxetine alongside rituximab for optimal pain management 1, 4

• Infection Risk: Rituximab likely increases slightly common infections compared with interferon beta, glatiramer acetate, and natalizumab, but absolute risk remains small 3

• Treatment Failure: In cases of inadequate response, consider alternative immunosuppressive regimens or combination therapy based on the specific neurological condition 7, 9