What is the recommended rituximab (Rituxan) protocol for a patient with Pemphigus vulgaris?

Rituximab Protocol for Pemphigus Vulgaris

Induction Dosing

Administer rituximab as two 1,000 mg intravenous infusions separated by 2 weeks, combined with a tapering course of glucocorticoids starting at 0.5-1 mg/kg/day prednisolone. 1, 2, 3

This represents the FDA-approved pemphigus vulgaris protocol and differs from the older rheumatoid arthritis protocol (2 x 1g) or lymphoma protocol (375 mg/m² weekly x 4 weeks). 1, 3 The pemphigus-specific dosing achieves 89% complete remission off all treatment at 2 years, which is dramatically superior to prednisolone alone (28% remission). 4, 2

Premedication Requirements

Administer methylprednisolone 100 mg intravenously (or equivalent) 30 minutes prior to each rituximab infusion, plus acetaminophen and an antihistamine. 1

Mandatory Pre-Treatment Screening

Before initiating rituximab, you must complete: 2, 3

• Hepatitis B screening (surface antigen, core antibody, surface antibody) - reactivation can be fatal
• Chest radiograph for active or latent tuberculosis
• IGRA testing - if positive, start latent TB treatment and delay rituximab for at least 1 month
• Baseline immunoglobulin levels (IgG, IgM, IgA) 2
• Complete blood count, liver and renal function tests 2

Glucocorticoid Tapering Strategy

Start prednisolone at 0.5-1 mg/kg/day and taper as clinical response permits. 2, 3 This short-term corticosteroid approach combined with rituximab produces fewer severe adverse events compared to prolonged high-dose prednisolone monotherapy. 4

Management of Adjuvant Immunosuppressants

If the patient is already on azathioprine, mycophenolate mofetil, or tacrolimus, reduce doses when adding rituximab to minimize infection risk. 4, 2, 3

Specific dose reduction for tacrolimus: reduce to 2-3 mg/day targeting trough levels of 6 ng/mL. 2 This dose reduction is mandatory, not optional - continuing full-dose conventional immunosuppressants with rituximab significantly increases severe infection risk. 2, 3

Infection Prophylaxis

Consider PCP prophylaxis during and following rituximab treatment, particularly when using triple immunosuppression or with additional risk factors. 1, 2, 3

The FDA label states PCP prophylaxis "should be considered" for pemphigus vulgaris patients, while it is mandatory for GPA/MPA patients (at least 6 months post-treatment). 1 Monitor for tuberculosis symptoms monthly during treatment and for at least 12 months after completion. 2

Expected Clinical Timeline

• Initial improvement: within 6 weeks of rituximab administration 4, 2, 5
• Complete healing: averages 15 weeks (range 3-8 weeks) 2, 5
• Disease control: mean 11 months 2, 3
• Complete remission: mean 58 months 2, 3

Clinical remission on therapy occurs in 90-95% of patients, with complete resolution within 3-4 months. 6

Maintenance Protocol

Administer rituximab 500 mg intravenous infusion at Month 12, then every 6 months thereafter or based on clinical evaluation. 1

This maintenance dosing is lower than the induction dose and helps prevent relapse while minimizing cumulative immunosuppression.

Relapse Management

Relapse occurs in 40-65% of patients, typically 13-17 months after rituximab (range 13-145 months). 4, 2, 3, 5

For relapse, administer rituximab 1,000 mg intravenous infusion and consider resuming or increasing glucocorticoid dose. 1 Subsequent rituximab infusions may be given no sooner than 16 weeks following the previous infusion. 1

Retreatment with rituximab during relapses results in complete or partial remission in the majority of patients, with maintained efficacy and safety. 7

Monitoring Schedule

• Complete blood count: every 2-4 weeks initially after starting rituximab 2
• Liver and renal function tests: regularly throughout treatment 2
• TB symptom monitoring: monthly during treatment and for at least 12 months after 2

Critical Safety Considerations

Temporarily discontinue tacrolimus or other adjuvant immunosuppressants if serious infection develops requiring antibiotics. 3, 5 Resume at reduced doses once infection resolves. 3

Serious adverse events occur in approximately 5 patients per case series (range 2-9), most commonly infections potentially resulting in septicemia. 6 The mortality rate related to rituximab averages 2 patients per large case series. 6 However, these data predominantly reflect treatment-refractory patients on multiple immunosuppressants, not first-line use with short-term corticosteroids.

First-Line vs. Refractory Disease

Rituximab should be used as first-line therapy in combination with short-term prednisolone for newly diagnosed pemphigus vulgaris, not reserved for treatment-refractory cases. 4, 2

This represents a major paradigm shift. 2 Early rituximab use reduces adverse effects by 94% compared to classic corticosteroid-centered therapy (P = 0.001). 8 The British Association of Dermatologists' 2017 guidelines support this approach based on a single unblinded RCT showing superior efficacy, though they downgraded the recommendation to Grade B due to lack of blinding and higher dropout rates in the prednisolone-only arm. 4

Alternative Protocols for Rituximab-Resistant Cases

For the rare patient resistant to rituximab: 4, 5

• Veltuzumab (humanized anti-CD20 antibody): two subcutaneous injections 2 weeks apart 4, 2
• Immunoadsorption combined with rituximab: reduces circulating desmoglein antibody levels by up to 95% when administered daily over three consecutive days 2, 5

Critical Pitfalls to Avoid

• Do not delay rituximab until after multiple failed conventional therapies - early use provides better outcomes (89% vs. 28% remission) and fewer adverse effects 4, 2
• Do not continue full-dose conventional immunosuppressants when adding rituximab - dose reduction is mandatory to prevent severe infections 4, 2, 3
• Do not skip hepatitis B screening - reactivation can be fatal 2, 3
• Do not use the lymphoma protocol (375 mg/m² weekly x 4) - the pemphigus-specific protocol (2 x 1,000 mg) is FDA-approved and preferred 1, 3