What is the best alternative treatment for a patient with vasculitis who received the first dose of rituximab (rituximab) but cannot afford the second dose due to cost?

Switch to Cyclophosphamide for Remission Induction

For a patient with vasculitis who received only one dose of rituximab and cannot afford to complete the standard 4-week induction course, you should switch to cyclophosphamide combined with glucocorticoids to complete remission induction. This approach is supported by major guidelines that establish cyclophosphamide and rituximab as equally effective, interchangeable first-line agents for ANCA-associated vasculitis 1.

Rationale for Switching to Cyclophosphamide

• Cyclophosphamide is non-inferior to rituximab for remission induction in severe vasculitis, based on randomized controlled trials (RAVE and RITUXVAS) 1, 2.

• Guidelines explicitly support switching between agents when one therapy cannot be completed or is refractory 1, 3.

• Oral cyclophosphamide is specifically recommended when cost is an important factor, making it the ideal alternative in this scenario 1.

Cyclophosphamide Dosing Options

You have two evidence-based regimens to choose from:

Oral Cyclophosphamide (Cost-Effective Option)

• 2 mg/kg/day for 3 months, continuing for ongoing activity up to a maximum of 6 months 1, 3
• Dose reductions for age: 1.5 mg/kg/day if ≥60 years; 1.0 mg/kg/day if ≥70 years 1
• Reduce by 0.5 mg/kg/day if GFR <30 ml/min/1.73 m² 1

Intravenous Cyclophosphamide (If Infusion Access Available)

• 15 mg/kg at weeks 0,2,4,7,10,13 (with additional doses at weeks 16,19,21,24 if required) 1
• Dose reductions for age: 12.5 mg/kg if ≥60 years; 10 mg/kg if ≥70 years 1
• Reduce by 2.5 mg/kg if GFR <30 ml/min/1.73 m² 1

Essential Supportive Measures

Mandatory Prophylaxis

• Pneumocystis jirovecii prophylaxis with trimethoprim/sulfamethoxazole (800/160 mg on alternate days or 400/80 mg daily) is required throughout cyclophosphamide therapy 1, 2, 4, 3.
• Alternatives if contraindicated: dapsone or atovaquone 1.

Bladder Protection

• MESNA (2-mercaptoethanesulfonate sodium) should be given orally or IV with each cyclophosphamide dose to prevent hemorrhagic cystitis by binding the toxic metabolite acrolein 1, 3.
• Encourage high fluid intake on treatment days to dilute urinary metabolites 1.
• Antiemetic therapy should be routinely administered with IV cyclophosphamide 1, 3.

Glucocorticoid Continuation

• Continue high-dose glucocorticoids with standardized tapering per the PEXIVAS protocol: starting at 50-75 mg prednisolone daily (weight-based), tapering to 5 mg daily by weeks 23-52 1, 3.

Monitoring Requirements

• Regular blood counts to monitor for leucopenia, with dose adjustments or discontinuation as needed 1.
• Watch for cumulative cyclophosphamide toxicity, particularly if the patient has received prior cyclophosphamide 1.

Maintenance Therapy Planning

• After achieving remission with cyclophosphamide (typically 3-6 months), switch to maintenance therapy with azathioprine or methotrexate 3.
• Maintenance duration should be 18 months to 4 years after remission induction 1.
• If rituximab becomes affordable later, it can be considered for maintenance therapy as it is superior to azathioprine 2, 4.

Critical Caveat

One dose of rituximab is insufficient for remission induction - the standard regimen requires 375 mg/m² weekly for 4 weeks 1, 2. The incomplete rituximab course means the patient has not achieved adequate B-cell depletion for disease control, making prompt initiation of cyclophosphamide essential to prevent disease progression and organ damage.