What is the recommended induction dose of rituximab (Rituxan) for patients with inflammatory myositis?

Rituximab Induction Dosing for Inflammatory Myositis

For adults with inflammatory myositis, administer rituximab 1000 mg IV on day 0 and repeat 1000 mg IV on day 15 (two weeks apart). 1

Primary Dosing Regimens

Two evidence-based induction protocols exist for rituximab in inflammatory myositis:

Fixed-Dose Regimen (Preferred for Adults)

• 1000 mg IV on day 0, repeated on day 15 1
• This is the dosing used in the landmark Rituximab in Myositis (RIM) trial, which demonstrated 83% favorable response in 200 pediatric and adult patients with refractory disease over 44 weeks 1
• This regimen showed significant reduction in muscle enzyme levels and improvements in strength, disease activity, and quality of life scores at 27.1 months follow-up 1

Body Surface Area-Based Regimen (Alternative)

• 375 mg/m² IV once weekly for 4 consecutive weeks 1, 2
• This protocol demonstrated improvement in muscle strength, reduction of CK levels, and improved cutaneous and pulmonary disease after 12 weeks in open-label trials 1
• Recent meta-analysis showed similar response rates between the two regimens: 68% for the 1000 mg protocol versus 71% for the 375 mg/m² protocol 3

Pre-Treatment Screening Requirements

Before initiating rituximab, obtain the following mandatory baseline assessments:

• Immunoglobulin levels (IgG, IgM, IgA) 1, 2
• Hepatitis B and C antibody screening 1, 2
• Latent tuberculosis screening 1, 2
• Complete blood count with differential 2

Clinical Context and Patient Selection

Rituximab is indicated for patients with:

• Refractory inflammatory myositis despite corticosteroids and at least one conventional immunosuppressant 1, 4
• Severe disease complications including interstitial lung disease, severe cutaneous manifestations, or organ involvement 1
• Steroid-dependent disease requiring unacceptably high corticosteroid doses 5

The overall pooled response rate across all myositis subtypes is 70%, with complete remission in 13% and partial response in 48% of patients 3. Response rates by subtype include: polymyositis 69%, dermatomyositis 67%, antisynthetase syndrome 70%, juvenile dermatomyositis 60%, and immune-mediated necrotizing myopathy 86% 3.

Monitoring and Safety Considerations

Expected Timeline for Response

• CK decrease: Observed at 1 month post-infusion 6
• CK normalization: Averages 4.6 months (range 2.6-7.7 months) 6
• Muscle strength improvement: Progressive over 12 weeks 1

Common Adverse Events

• Infusion reactions: Occur in up to 77% during first infusion, manageable with premedication (antipyretic and antihistamine) 2
• Infections: Most common serious adverse event, particularly respiratory tract infections (12.4% incidence) 7, 3
• Cytopenias: Monitor CBC at 2-4 month intervals during treatment 2

Critical Safety Warnings

• Progressive multifocal leukoencephalopathy (PML): Reported in rheumatic patients treated with rituximab; maintain high index of suspicion for any CNS abnormalities 1
• Hepatitis B reactivation: Screen all patients before treatment 2
• Severe infections: Use caution in immunosuppressed patients 1

Maintenance and Retreatment

For patients achieving complete response:

• Maintenance dosing: Rituximab may be repeated every 24 weeks (6 months) based on clinical response 5, 2
• Low-dose maintenance: Single dose of 1000 mg every 6 months has shown effectiveness in maintaining remission after standard induction 4
• Retreatment timing: Myositis recurrence typically occurs 6-10 months post-infusion when circulating B cells return, though this does not always correlate with CD19+ cell levels 6, 7

Corticosteroid Tapering

Following rituximab induction, expect significant corticosteroid dose reduction:

• Average daily prednisone decreased from 16.7 mg to 4 mg after rituximab infusion in clinical studies 6
• 72% of patients achieving complete or partial response were able to decrease mean daily corticosteroid dose 4