Is maintenance therapy with Rituxan (rituximab) still required in patients with ANCA-associated vasculitis being treated with Avacopan (pegcetacoplan)?

Maintenance Therapy with Rituximab in ANCA-Associated Vasculitis Patients Using Avacopan

Yes, maintenance therapy with rituximab is still required in patients with ANCA-associated vasculitis (AAV) being treated with avacopan. 1 Avacopan serves as an alternative to glucocorticoids in the induction phase but does not replace the need for maintenance immunosuppression.

Understanding Avacopan's Role in AAV Treatment

Avacopan is a C5a receptor inhibitor that can be used as an alternative to glucocorticoids during the induction phase of AAV treatment. According to the 2024 KDIGO guidelines:

• Avacopan is administered at 30 mg twice daily in combination with either rituximab or cyclophosphamide for induction therapy 1
• It primarily benefits patients with increased risk of glucocorticoid toxicity and those with lower GFR who may benefit from greater GFR recovery 1
• Avacopan replaces glucocorticoids but does not replace the need for immunosuppressive therapy 1, 2

Maintenance Therapy Requirements

The 2024 KDIGO guidelines clearly state:

1. Following rituximab induction, maintenance immunosuppressive therapy should be given to most patients 1
2. The optimal duration of remission therapy is between 18 months and 4 years after induction of remission 1
3. Maintenance therapy is recommended with either rituximab or azathioprine after induction of remission (1C recommendation) 1

Rituximab Maintenance Protocols

When using rituximab for maintenance, the KDIGO guidelines recommend one of two protocols:

1. MAINRITSAN scheme: 500 mg × 2 at complete remission, and 500 mg at months 6,12, and 18 thereafter 1
2. RITAZAREM scheme: 1000 mg infusion after induction of remission, and at months 4,8,12, and 16 after the first infusion 1

Rationale for Continued Maintenance Therapy

Even when avacopan is used in the induction phase:

• Extrarenal AAV can and does relapse, requiring consolidation of remission with maintenance therapy 1
• The ADVOCATE trial (which studied avacopan) did not address treatment beyond 52 weeks 2, 3
• Long-term studies show that rituximab maintenance therapy significantly reduces relapse rates compared to other maintenance options 4

Special Considerations

1. Potential exception: In patients with kidney failure, anti-MPO positivity, and no extrarenal symptoms, long-term maintenance may not be necessary, and treatment should be assessed individually 1

2. Relapse risk factors to consider when deciding on maintenance therapy duration:

   • PR3-ANCA positivity 5
   • B cell return within 12 months of last rituximab infusion 5
   • Switch from ANCA negativity to positivity 5

Common Pitfalls to Avoid

• Premature discontinuation: Stopping maintenance therapy too early can lead to relapses, which occurred at a median of 34.4 months after the last rituximab infusion in one study 5
• Overreliance on ANCA titers: While useful, ANCA titers alone should not guide maintenance therapy decisions
• Inadequate monitoring: Regular assessment of disease activity, B cell counts, and ANCA status is essential during maintenance therapy

Conclusion

Based on the most recent 2024 KDIGO guidelines, maintenance therapy with rituximab is still required in patients with ANCA-associated vasculitis being treated with avacopan. Avacopan serves as a glucocorticoid replacement during induction but does not eliminate the need for maintenance immunosuppression to prevent disease relapse and improve long-term outcomes.