What is the role of Rituximab (rituximab) in treating ANCA (Anti-Neutrophil Cytoplasmic Antibody)-associated vasculitis?

Mechanism of Action of Rituximab in ANCA Vasculitis

Rituximab works in ANCA vasculitis by selectively depleting CD20-positive B cells, which are central to the pathogenesis of the disease through antibody production and immune dysregulation. 1

Primary Mechanism of Action

Rituximab is a chimeric monoclonal antibody that specifically targets the CD20 antigen expressed on the surface of B lymphocytes. Its therapeutic effects in ANCA vasculitis occur through several mechanisms:

• B cell depletion: Rituximab binds to CD20 on B cells and eliminates them through:

  • Antibody-dependent cellular cytotoxicity
  • Complement-dependent cytotoxicity
  • Direct induction of B cell apoptosis

• Reduction of ANCA production: By eliminating B cells, rituximab reduces the production of pathogenic ANCA antibodies that target neutrophil components (proteinase 3 and myeloperoxidase) 2

• Disruption of immune dysregulation: Beyond antibody reduction, rituximab affects:

  • Antigen presentation by B cells to T cells
  • Cytokine production that drives inflammation
  • Restoration of immune homeostasis and tolerance 3

Clinical Application in ANCA Vasculitis

Rituximab has proven efficacy in ANCA vasculitis in several key scenarios:

Induction Therapy

• Newly diagnosed disease: Rituximab (375 mg/m² weekly for 4 weeks) is non-inferior to cyclophosphamide for remission induction 4, 5
• Severe disease: Particularly effective in patients with PR3-ANCA positivity 1

Maintenance Therapy

• Relapse prevention: Two recommended dosing protocols 1:
  1. MAINRITSAN protocol: 500 mg × 2 at remission, then 500 mg at months 6,12, and 18
  2. RITAZAREM protocol: 1000 mg after induction, then at months 4,8,12, and 16

Relapsing Disease

• Superior efficacy: Rituximab shows higher remission rates (67% vs 42%) compared to cyclophosphamide in relapsing disease 5
• Preferred agent: Guidelines specifically recommend rituximab over cyclophosphamide for relapsing ANCA vasculitis 1

Refractory Disease

• Alternative approach: For patients not responding to cyclophosphamide, switching to rituximab can achieve remission in 75-90% of cases 6
• Combination therapy: In severe refractory cases, rituximab may be combined with plasma exchange 1

Practical Considerations

• Monitoring: B cell counts and immunoglobulin levels should be monitored, though B cell return doesn't consistently predict relapse (only in 52% of cases) 6
• Safety profile: Most common adverse reactions include infusion reactions (12-32% of patients), infections (53-62%), and hypogammaglobulinemia 4
• Special populations: Preferred over cyclophosphamide in patients of reproductive age due to fertility preservation 1

Limitations and Precautions

• Infection risk: Serious infections occur in approximately 11% of patients 4
• Hypogammaglobulinemia: IgM levels typically decrease, though IgG levels generally remain stable 6
• Progressive multifocal leukoencephalopathy: Rare but serious potential complication requiring vigilance 3

Rituximab has revolutionized the treatment of ANCA vasculitis by providing an effective alternative to cyclophosphamide with potentially fewer long-term toxicities, particularly for patients with relapsing disease or concerns about fertility preservation.