Rituximab Dosing for IgG4-Related Disease
For IgG4-related disease, administer rituximab 1000 mg IV on day 0, repeated 1000 mg IV on day 15, with maintenance dosing of 1000 mg IV every 6 months, including premedication with methylprednisolone and an antihistamine. 1
Primary Induction Regimen
The standard rituximab induction protocol consists of:
- Two infusions of 1000 mg administered 15 days apart 1, 2
- Premedication with methylprednisolone and an antihistaminic agent before each infusion 1
- This regimen has demonstrated >95% response rates in IgG4-RD case series 1
An alternative dosing schedule of 375 mg/m² IV once weekly for 4 consecutive weeks has also been used successfully, particularly in orbital and other organ-specific IgG4-RD 3, 4. However, the 1000 mg × 2 regimen is more commonly recommended in current guidelines for systemic disease 1, 2.
Maintenance Therapy
Rituximab maintenance should be administered every 6 months to prevent relapse, given that at least 60% of IgG4-RD patients relapse after initial treatment 1, 2. The maintenance regimen consists of:
- Two infusions of 1000 mg rituximab 15 days apart, repeated every 6 months 1
- Continue maintenance based on clinical response and disease activity 2
- One case series documented disease relapse when the dosing interval was extended beyond 6 months, with swift remission achieved upon returning to the standard interval 3
Clinical Context for Rituximab Use
Rituximab is specifically indicated for:
- Patients who relapse during or after corticosteroid tapering 1
- Steroid-dependent or steroid-resistant disease 1, 3
- Multisystem or complex IgG4-RD 1, 2
- Patients who fail first-line therapy with corticosteroids and conventional immunosuppressants (azathioprine, mycophenolate mofetil) 1
The evidence strongly supports rituximab as the preferred second-line agent, with case series showing complete clinical resolution in 60-100% of patients within 2 months of initiation 3, 5.
Pre-Treatment Requirements
Before initiating rituximab, obtain:
- Immunoglobulin levels (IgG, IgA, IgM) to identify pre-existing hypogammaglobulinemia 6, 7
- Hepatitis B and C antibody screening, including hepatitis B core antibody 6, 7
- Latent tuberculosis screening 6
- Complete blood count with differential 6, 7
For patients who are hepatitis B core antibody positive, prophylactic antiviral therapy is mandatory to prevent hepatitis B reactivation 6.
Monitoring During Treatment
- Serum IgG4 levels should NOT be used to monitor treatment response or guide therapy adjustments, as levels may not correlate with disease activity 2
- Monitor clinical improvement (resolution of symptoms, normalization of organ function) and radiological findings 1, 2
- Complete blood count should be monitored at 2-4 month intervals for cytopenias 6, 7
- B-cell depletion is sustained for 6-12 months, with recovery beginning around 6 months 7
Response and Outcomes
Clinical improvement typically occurs within 1 month of starting rituximab, with:
- All patients in one series able to discontinue prednisone and DMARDs following rituximab 5
- Significant decreases in IgG4 concentrations observed specifically for the IgG4 subclass 5
- Complete or partial clinical resolution in 100% of cases within 2 months 3
- Serial treatments leading to progressive declines in serum IgG4 and better disease control 5
Safety Considerations
Critical warnings include:
- Progressive multifocal leukoencephalopathy (rare but fatal complication requiring vigilance) 1, 7
- Hepatitis B reactivation (prevented with prophylactic antivirals in at-risk patients) 6, 7
- Infusion reactions (occur in up to 77% during first infusion, manageable with premedication) 6
- Serious infections, particularly with prolonged B-cell depletion or hypogammaglobulinemia 7
Adverse effects in IgG4-RD series have been minimal, including only fatigue and orbital discomfort 3, with excellent tolerability reported across multiple studies 4, 5, 8.
Common Pitfalls to Avoid
- Do not delay rituximab in steroid-dependent patients: Early initiation prevents cumulative steroid toxicity in this typically elderly population 1, 9
- Do not extend maintenance intervals beyond 6 months without close monitoring, as relapse risk increases 3
- Do not use serum IgG4 alone to determine treatment response: Clinical and radiological improvement are the primary endpoints 2
- Do not withhold rituximab in patients with advanced fibrosis: While fibrotic disease may not reverse, rituximab prevents progression to new organs 5