What is the updated protocol for intravenous (IV) infusion of rituximab (rituximab) in the treatment of pemphigus vulgaris?

Updated Rituximab Protocol for Pemphigus Vulgaris

The current standard protocol for rituximab in pemphigus vulgaris is two 1,000 mg intravenous infusions separated by 2 weeks, combined with a tapering course of glucocorticoids, followed by maintenance dosing of 500 mg at month 12 and every 6 months thereafter. 1

Induction Protocol

Initial Dosing

• Administer rituximab 1,000 mg IV on day 1 and day 15 (2 weeks apart) 1
• This represents the FDA-approved pemphigus vulgaris protocol, which differs from the older rheumatoid arthritis protocol (2 x 1 g infusions) previously referenced in earlier guidelines 2, 1

Concurrent Glucocorticoid Therapy

• Combine rituximab with prednisolone starting at 0.5-1 mg/kg/day for most cases 3
• This short-term glucocorticoid approach achieves 89% complete remission off all treatment at 2 years 3, 4

Premedication Requirements

• Administer methylprednisolone 100 mg IV (or equivalent) 30 minutes prior to each rituximab infusion 1
• Add acetaminophen and an antihistamine before each infusion 1

Maintenance Protocol

Long-Term Dosing

• Administer rituximab 500 mg IV at month 12, then every 6 months thereafter based on clinical evaluation 1
• Subsequent infusions should not be given sooner than 16 weeks after the previous dose 1

Relapse Management

Treatment of Recurrence

• Administer rituximab 1,000 mg IV as a single infusion upon relapse 1
• Consider resuming or increasing glucocorticoid dose based on clinical severity 1
• Subsequent infusions may be given no sooner than 16 weeks following the previous infusion 1
• Expect relapse in 40-65% of patients, typically occurring 13-17 months after rituximab (range 13-145 months) 3, 4

Adjuvant Immunosuppression Management

Dose Reduction Strategy

• Continue existing adjuvant immunosuppressants (azathioprine, mycophenolate mofetil) but reduce doses to minimize infection risk 3, 4
• For tacrolimus specifically, reduce to 2-3 mg/day targeting trough levels of 6 ng/mL when combined with rituximab 3
• This dose reduction is mandatory to prevent severe infections when adding rituximab to existing immunosuppression 3

Expected Clinical Response

Timeline to Improvement

• Clinical improvement typically begins within 6 weeks of rituximab administration 3, 4
• Complete healing of skin and mucosal lesions averages 15 weeks (range 3-8 weeks) 3
• Mean time to disease control is 11 months, with remission achieved at 58 months on average 3

Mandatory Pre-Treatment Screening

Infectious Disease Evaluation

• Perform hepatitis B screening before rituximab initiation, as reactivation can be fatal 3
• Obtain chest radiograph to evaluate for active or latent tuberculosis 3
• If IGRA-positive, initiate latent TB treatment and delay rituximab for at least 1 month after starting anti-tubercular therapy 3

Monitoring Protocol

Laboratory Surveillance

• Complete blood count every 2-4 weeks initially after starting rituximab 3
• Monitor liver and renal function tests regularly 3
• Monitor for TB symptoms monthly during treatment and for at least 12 months after completion 3

Infection Prophylaxis

• Consider PCP prophylaxis during and following rituximab treatment, particularly when using triple immunosuppression or with additional risk factors 3, 1
• PCP prophylaxis with trimethoprim/sulfamethoxazole should be strongly considered given the infection risk 1

Management of Serious Infections

Immunosuppressant Adjustment

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

Alternative Protocols for Refractory Cases

Rituximab-Resistant Disease

• For patients resistant to or intolerant of rituximab, consider immunoadsorption combined with rituximab 4
• Immunoadsorption can reduce circulating desmoglein antibody levels by up to 95% when administered daily over three consecutive days 4
• Novel anti-CD20 agents like veltuzumab (subcutaneous) may benefit rituximab-resistant patients 3, 4

Critical Pitfalls to Avoid

• Do not delay rituximab until after multiple failed conventional therapies in appropriate candidates, as early use provides better outcomes (89% complete remission at 2 years) and fewer adverse effects 3
• Do not continue full-dose conventional immunosuppressants when adding rituximab—dose reduction is mandatory to prevent severe infections 3
• Do not administer subsequent rituximab doses sooner than 16 weeks after the previous infusion 1
• Do not skip pre-treatment hepatitis B and tuberculosis screening, as reactivation can be fatal 3