What is the recommended maintenance treatment regimen for a patient with ANCA (Antineutrophil Cytoplasmic Antibody)-associated vasculitis?

Maintenance Treatment in ANCA-Associated Vasculitis

For maintenance therapy after achieving remission in ANCA-associated vasculitis, use either rituximab OR azathioprine plus low-dose glucocorticoids, with rituximab preferred for relapsing disease and PR3-ANCA positivity. 1

Primary Maintenance Options

Rituximab Regimens

Rituximab is the preferred maintenance agent, particularly for patients with relapsing disease or PR3-ANCA positivity. 1

Two validated dosing protocols exist:

• MAINRITSAN scheme: 500 mg × 2 doses at complete remission, then 500 mg at months 6,12, and 18 1
• RITAZAREM scheme: 1000 mg infusion after induction, then at months 4,8,12, and 16 (specifically studied in relapsing AAV) 1

Rituximab demonstrated superior relapse prevention compared to azathioprine, with major relapse rates of 5% versus 29% at 28 months. 2

Azathioprine Regimen

Start azathioprine at 1.5-2 mg/kg/day at complete remission, continue until 1 year after diagnosis, then decrease by 25 mg every 3 months. 1

For extended therapy: Continue at 1.5-2 mg/kg/day for 18-24 months, then decrease to 1 mg/kg/day until 4 years after diagnosis, then taper by 25 mg every 3 months. 1

Azathioprine is preferred when baseline IgG is low (<300 mg/dL) or rituximab availability is limited. 1

Concomitant Glucocorticoid Therapy

All maintenance regimens require low-dose glucocorticoids at 5-7.5 mg/day for 2 years, then slowly reduced by 1 mg every 2 months. 1

This applies regardless of whether rituximab, azathioprine, or MMF is used for maintenance. 1

Duration of Maintenance Therapy

The optimal duration of maintenance therapy is between 18 months and 4 years after induction of remission. 1

Following rituximab induction, maintenance immunosuppressive therapy should be given to most patients. 1

Alternative Maintenance Agents

Mycophenolate Mofetil (MMF)

Consider MMF 2000 mg/day (divided doses) as an alternative for patients intolerant of azathioprine, continuing for 2 years at complete remission. 1

Methotrexate

Methotrexate is an alternative to azathioprine but should NOT be used in patients with GFR <60 ml/min/1.73 m². 1

Factors Influencing Choice Between Rituximab and Azathioprine

Rituximab is strongly preferred for:

• Relapsing disease (67% remission rate vs 42% with cyclophosphamide) 1
• PR3-ANCA subgroup 1
• History of prior relapse 1
• ANCA-positive status at end of induction 1

Azathioprine may be preferred for:

• Low baseline IgG (<300 mg/dL) 1
• Limited rituximab availability 1
• Cost considerations in resource-limited settings 1

Management of Relapsing Disease

Patients with relapsing disease should be reinduced, preferably with rituximab. 1

Rituximab achieved >90% remission rates by 4 months in relapsing GPA/MPA patients. 1

Common Pitfalls and Monitoring

When considering withdrawal of maintenance therapy, assess relapse risk factors including:

• Granulomatosis with polyangiitis diagnosis 1
• PR3-ANCA subgroup 1
• Higher serum creatinine at baseline 1
• More extensive disease or ENT involvement 1
• History of relapse 1
• ANCA positive at end of induction or rising ANCA 1
• Lower cyclophosphamide exposure 1

Patients should be informed of the need for prompt attention if symptoms recur after therapy withdrawal. 1

The cumulative cyclophosphamide dose already given should be considered, as cumulative doses above 36 g are associated with malignancy risk. 1

Safety Considerations

Infection rates during maintenance therapy are approximately 25-28 per 100 patient-years, with serious infection rates of 10-11%. 3

Hypogammaglobulinemia occurs in 27-58% of rituximab-treated patients at 6 months, requiring monitoring of immunoglobulin levels. 3

Serious adverse events were less frequent with reduced-dose glucocorticoid regimens (27.5% vs 46.2%) without compromising efficacy. 4