What is the recommended treatment protocol for a patient with moderate to severe pemphigus vulgaris using rituximab (anti-CD20 agent)?

Rituximab Treatment Protocol for Pemphigus Vulgaris

For moderate to severe pemphigus vulgaris, administer rituximab 1 g intravenously on days 1 and 15 (rheumatoid arthritis protocol), combined with prednisolone starting at 0.5-1 mg/kg/day, which achieves 89% complete remission off all treatment at 2 years. 1, 2, 3

Dosing Regimen

Initial Treatment Course

• Administer rituximab 1 g IV on day 1 and day 15 (2 weeks apart), which is the rheumatoid arthritis protocol recommended by the British Association of Dermatologists 1
• Combine with oral prednisolone 0.5-1 mg/kg/day initially, then taper as clinical improvement occurs 1, 2
• The FDA label confirms rituximab is indicated for moderate to severe pemphigus vulgaris and must be administered only as an intravenous infusion, never as a push or bolus 4

Alternative Dosing (Less Commonly Used)

• The lymphoma protocol (375 mg/m² weekly for 4 weeks) has been studied but the 2-dose regimen is now preferred based on guideline recommendations 1, 5

Infusion Administration Details

Pre-Infusion Requirements

• Screen for hepatitis B (HBsAg and anti-HBc) before initiating treatment, as reactivation can be fatal 6, 4
• Obtain baseline complete blood count with differential and platelets 4
• Obtain chest radiograph to evaluate for active or latent tuberculosis 2
• Premedicate before each infusion per standard protocols 4

Infusion Rate Protocol

• First infusion: Start at 50 mg/hr, increase by 50 mg/hr increments every 30 minutes if no infusion toxicity occurs, up to maximum 400 mg/hr 4
• Subsequent infusions: Start at 100 mg/hr, increase by 100 mg/hr increments every 30 minutes, up to maximum 400 mg/hr 4
• Administer only in a facility with appropriate medical support to manage severe infusion reactions 4

Corticosteroid Management

Prednisolone Dosing Strategy

• Start prednisolone at 0.5-1 mg/kg/day (or 1 mg/kg/day in more severe cases) 1
• Increase in 50-100% increments every 5-7 days if blistering continues 1
• Once remission is induced (no new blisters, healing of majority of lesions), taper dose with goal of reducing to ≤10 mg daily 1
• The rituximab combination allows for significantly shorter corticosteroid exposure compared to standard high-dose prednisone alone 7

Adjuvant Immunosuppressant Management

Dose Reduction Strategy

• Reduce doses of concurrent immunosuppressants (azathioprine, mycophenolate mofetil) when adding rituximab to minimize infection risk 2, 3
• If serious infection develops requiring antibiotics, temporarily discontinue adjuvant immunosuppressants and resume at reduced doses once infection resolves 2
• Consider PCP prophylaxis during and after rituximab, particularly with triple immunosuppression or additional risk factors 6

Expected Clinical Response Timeline

Response Milestones

• Clinical improvement typically begins within 6 weeks of rituximab administration 3, 6, 8
• Complete healing of skin and mucosal lesions averages 15 weeks 2, 8
• Mean time to disease control is 11 months 2, 6
• Average time to remission is 58 months 2, 6

Monitoring During Treatment

Laboratory Surveillance

• Obtain CBC with differential and platelets at 2-4 month intervals during rituximab therapy 4
• Continue monitoring for cytopenias after final dose until resolution 4
• Monitor for late-onset neutropenia, which is the primary hematologic concern (not thrombocytopenia) 6

Relapse Management

Expected Relapse Patterns

• Relapse occurs in 40-65% of patients, typically at 13-17 months after rituximab (range 13-145 months) 2, 3, 6
• For relapse, retreat with the same rituximab protocol (1 g on days 1 and 15) combined with topical or systemic corticosteroids 8, 5
• Some patients may require 2 courses of rituximab for sustained remission 9

Treatment-Resistant Cases

Alternative Strategies

• For patients resistant to or intolerant of rituximab, consider immunoadsorption combined with rituximab, which can reduce circulating desmoglein antibody levels by up to 95% 3, 6
• Immunoadsorption is administered daily over 3 consecutive days 3

Critical Safety Considerations

Major Warnings

• Severe mucocutaneous reactions (including fatal) can occur 4
• HBV reactivation can result in fulminant hepatitis, hepatic failure, and death 4
• Progressive multifocal leukoencephalopathy (PML), including fatal PML, can occur 4
• Rituximab carries a 3% death rate in uncontrolled trials for other autoimmune conditions 6
• Infectious complications are significant, particularly when combined with multiple immunosuppressants 10

Common Pitfalls to Avoid

• Do not use rituximab monotherapy in patients requiring urgent disease control—the response is delayed compared to combination therapy 2, 3
• Do not withdraw treatment prematurely—relapse rates are high if treatment is stopped after only 1 year 1
• Do not fail to screen for hepatitis B—this is mandatory before initiating treatment 6, 4
• Do not continue full-dose adjuvant immunosuppressants—reduce doses when adding rituximab to minimize infection risk 2, 3