What is the role of Rituximab (rituximab) infusion in the treatment of Immunoglobulin A (IgA) vasculitis?

Rituximab for IgA Vasculitis

Rituximab is not a guideline-recommended therapy for IgA vasculitis, as this condition is fundamentally distinct from ANCA-associated vasculitis (AAV) where rituximab has established efficacy. However, emerging case series and observational data suggest rituximab may be effective for severe, refractory IgA vasculitis, particularly with nephritis, when conventional therapies fail.

Critical Distinction: IgA Vasculitis vs ANCA-Associated Vasculitis

• IgA vasculitis (formerly Henoch-Schönlein purpura) is NOT the same as ANCA-associated vasculitis 1
• The KDIGO 2024 and EULAR/ERA-EDTA guidelines specifically address AAV (granulomatosis with polyangiitis and microscopic polyangiitis), not IgA vasculitis 2, 1
• Rituximab has FDA approval and strong guideline support for AAV, but no formal guidelines exist for rituximab use in IgA vasculitis 1, 3

Evidence for Rituximab in IgA Vasculitis

Observational Data Shows Promise

The strongest available evidence comes from a 2018 multicenter observational study of 22 adult IgA vasculitis patients treated with rituximab:

• 90.9% achieved remission with median follow-up of 24 months 4
• Significant reductions in proteinuria (P < 0.0001), inflammatory markers, and prednisone requirements 4
• 35% relapse rate, but all responded to repeat rituximab dosing 4
• Generally well tolerated with stable kidney function 4

Systematic Review Findings

A 2020 systematic review of 35 IgA vasculitis patients (pediatric and adult) treated with rituximab demonstrated:

• 94.3% showed clinical improvement of any type 5
• 74.3% achieved sustained remission at end of follow-up 5
• Almost 90% had renal involvement, and 85.7% had disease resistant/refractory to glucocorticoids or other immunosuppressants 5
• Relapse rate of 37.1%, but repeat rituximab achieved good disease control in all cases 5
• Only 8.6% experienced minor adverse effects with no deaths 5

Clinical Scenarios Where Rituximab May Be Considered

Based on available evidence, rituximab should be reserved for:

1. Refractory or relapsing IgA vasculitis despite adequate trials of glucocorticoids and conventional immunosuppressants (cyclophosphamide, azathioprine, mycophenolate) 6, 4, 5

2. Severe nephritis with progressive renal impairment despite standard therapy 6, 4, 5

3. Contraindications to conventional immunosuppressive therapy (e.g., malignancy risk, severe infections, fertility concerns) 5

4. Glucocorticoid-dependent disease requiring unacceptably high doses to maintain remission 4, 5

Proposed Dosing Regimen (Extrapolated from AAV Data)

While no standardized protocol exists for IgA vasculitis, the following regimens have been used successfully:

• Standard lymphoma protocol: 375 mg/m² IV weekly for 4 consecutive weeks 6, 4
• Alternative AAV-based protocol: 1000 mg IV on days 1 and 15 (two doses) 7
• Maintenance dosing: 500 mg IV every 6 months for patients achieving remission 7

Premedication and prophylaxis:

• Antihistamine and acetaminophen before each infusion 3
• Trimethoprim-sulfamethoxazole (800/160 mg alternate days or 400/80 mg daily) for Pneumocystis jirovecii prophylaxis during and for 6 months after rituximab 2, 7
• Consider methylprednisolone 100-500 mg IV before first infusion 3

Monitoring Requirements

Baseline assessments:

• IgG, IgA, IgM levels (risk stratification for hypogammaglobulinemia) 2, 3
• Complete blood count, renal function, urinalysis with 24-hour proteinuria 4
• Hepatitis B and C screening (reactivation risk) 2

Follow-up monitoring:

• Immunoglobulin levels every 6 months during rituximab therapy 2
• Renal function and proteinuria monthly initially, then every 3 months 4
• B-cell counts (CD19/CD20) to guide re-dosing decisions 8

Critical Caveats and Pitfalls

Important limitations to recognize:

1. All evidence is observational - no randomized controlled trials exist for rituximab in IgA vasculitis 5

2. Selection bias in published cases - most reports involve severe, refractory disease, so efficacy in less severe cases is unknown 5

3. Hypogammaglobulinemia risk - 27-58% of AAV patients develop low immunoglobulin levels after rituximab, increasing infection risk 3

4. Relapse remains common (35-37%), though usually responds to repeat dosing 4, 5

5. Long-term safety data lacking - most follow-up is 2-4 years maximum 4, 5

6. Cost considerations - rituximab is expensive and may not be covered by insurance for off-label IgA vasculitis indication 2

Practical Algorithm for Decision-Making

Step 1: Confirm diagnosis

• Biopsy-proven IgA vasculitis with IgA-dominant immune deposits 6, 4

Step 2: Assess disease severity and treatment history

• Has patient failed adequate trial of glucocorticoids PLUS at least one conventional immunosuppressant? 5
• Is there progressive renal impairment (rising creatinine, worsening proteinuria)? 4
• Are there contraindications to standard therapy? 5

Step 3: If YES to Step 2, consider rituximab

• Discuss off-label use, limited evidence, and potential risks/benefits with patient
• Obtain baseline labs including immunoglobulins 2
• Initiate with 375 mg/m² weekly × 4 weeks OR 1000 mg × 2 doses 6, 4

Step 4: Monitor response

• Expect clinical improvement within 3-6 months 4, 5
• If remission achieved, consider maintenance dosing every 6 months 7
• If relapse occurs, repeat rituximab course typically effective 4, 5

This approach prioritizes patient safety while offering a potentially effective option when standard therapies have failed, recognizing the absence of high-quality evidence but the compelling observational data suggesting benefit in carefully selected patients.