What is the role of Rituximab (rituximab) in the treatment of dermatomyositis?

Rituximab in Dermatomyositis

Rituximab should be used as adjunctive therapy for refractory dermatomyositis that has failed to respond adequately to corticosteroids combined with conventional steroid-sparing agents (methotrexate, azathioprine, or mycophenolate mofetil). 1

When to Use Rituximab

Reserve rituximab for patients who demonstrate inadequate response after 12 weeks of high-dose corticosteroids plus a conventional DMARD (methotrexate 15-20 mg/m²/week, azathioprine 2-3 mg/kg/day, or mycophenolate mofetil 2-3 g/day). 1

Rituximab is particularly indicated for:

• Refractory muscle weakness despite conventional immunosuppression 1
• Persistent or severe skin disease that reflects ongoing systemic inflammation 1, 2
• Cardiac involvement in dermatomyositis 3
• Severe disease with major organ involvement (interstitial lung disease, extensive ulcerative skin disease) 1

Critical Timing Consideration

Clinicians must recognize that rituximab can take up to 26 weeks to demonstrate clinical effect. 1 This delayed onset means:

• Do not prematurely declare treatment failure before 6 months 1
• Maintain adequate corticosteroid coverage during this lag period 1
• Plan for continuation of existing immunosuppression initially 1

Dosing Protocol

For adults with dermatomyositis, administer rituximab 1000 mg intravenously on day 0 and day 14 (two doses, 2 weeks apart). 1, 4 This rheumatoid arthritis dosing protocol has demonstrated efficacy in multiple case series, with 72-75% of patients showing good response. 5, 2

For juvenile dermatomyositis:

• Children with body surface area ≤1.5 m²: 575 mg/m² per infusion 1
• Children with body surface area >1.5 m²: 750 mg/m² up to 1 g per infusion 1

Combination Therapy Strategy

Continue existing immunosuppressive agents when initiating rituximab, but strongly consider dose reduction to minimize cumulative infection risk. 6 The evidence shows:

• 79-97% of successful rituximab cases involved concomitant corticosteroids and/or immunosuppressants 1
• Dose reduction of adjuvant immunosuppressants is strongly recommended to decrease infection risk 6
• If using tacrolimus concurrently, reduce to 2-3 mg/day (targeting trough levels of 6 ng/mL) rather than standard 4-6 mg/day 6

Expected Clinical Response

Based on retrospective data and case series:

• 81.8% of patients show improvement in proximal muscle weakness at 6-month follow-up 2
• 72.2% demonstrate improvement in skin disease 2
• Average prednisone dose decreases from 18.9 mg to 11.0 mg after rituximab 2
• Creatine kinase normalization occurs at an average of 4.6 months (range 2.6-7.7 months) 4
• Median symptom-free interval between courses is 12 months (range 6-19 months) 5

Retreatment Protocol

Relapse occurs in approximately 40% of patients, typically 6-10 months after initial treatment. 5, 4 Important considerations:

• Need for retreatment does not correlate reliably with CD19+ B-cell levels 4
• Some patients remain disease-free despite B-cell reconstitution, while others relapse with persistent B-cell depletion 4
• Repeat the same dosing protocol (1000 mg × 2 doses, 2 weeks apart) for relapse 4

Mandatory Pre-Treatment Screening

Before initiating rituximab, obtain:

• Hepatitis B surface antigen, core antibody, and surface antibody (reactivation can be fatal) 1, 6, 7
• Baseline immunoglobulin levels (IgG, IgM, IgA) 1
• Hepatitis C antibody 1
• Tuberculosis screening (interferon-gamma release assay or PPD) 1
• Complete blood count, hepatic and renal function 7
• Pregnancy test if applicable 7

Critical Safety Monitoring

During and after rituximab administration:

• Monitor closely during first infusion for severe infusion reactions (hypoxia, pulmonary infiltrates, respiratory distress, myocardial infarction, cardiogenic shock) 7
• Complete blood count every 2-4 weeks initially 6
• Liver and renal function tests regularly 6
• Serial pulmonary function tests at 6-month intervals 7
• Infection surveillance given profound B-cell depletion 7

Serious Adverse Events to Anticipate

Progressive multifocal leukoencephalopathy (PML) has been reported in:

• Rheumatic patients treated with rituximab 1
• Myositis patients who have NOT received rituximab 1
• Maintain high suspicion for JC virus reactivation in any patient with new neurological symptoms 1

Rituximab-induced interstitial lung disease occurs with 15% fatality rate in systematic reviews 7. This creates a paradox when treating dermatomyositis with pulmonary involvement—the drug can both help and harm the lungs.

Infection risk is dramatically increased when combining rituximab with other immunosuppressants:

• Consider Pneumocystis prophylaxis with triple immunosuppression 6
• Temporarily discontinue tacrolimus or other immunosuppressants if serious infection develops requiring antibiotics 6
• Complete vaccinations before starting rituximab whenever possible 6

Special Populations Requiring Extra Caution

Reduce doses more aggressively or monitor more closely in:

• Advanced age 6
• Diabetes or other comorbidities impairing immune function 6
• Impaired renal function (may require dose reduction or avoidance of concomitant tacrolimus) 6
• History of recurrent infections 6

Common Pitfalls to Avoid

1. Do not declare rituximab failure before 26 weeks of treatment, as clinical response is delayed 1
2. Do not use full-dose tacrolimus (4-6 mg/day) when combining with rituximab—reduce to 2-3 mg/day 6
3. Do not skip hepatitis B screening—reactivation is potentially fatal 1, 6, 7
4. Do not continue full-dose immunosuppression during active serious infection—temporarily discontinue to reduce mortality risk 6
5. Do not assume B-cell levels predict need for retreatment—clinical relapse can occur with or without B-cell reconstitution 4

Position in Treatment Algorithm

The evidence supports this hierarchical approach:

First-line: High-dose corticosteroids (oral or IV) combined with methotrexate 15-20 mg/m²/week 1

Second-line (if inadequate response by 12 weeks): Consider intensification with:

• IV immunoglobulin (particularly for prominent skin features) 1
• Mycophenolate mofetil 1
• Ciclosporin A 1

Third-line (refractory disease): Rituximab as adjunctive therapy 1

Also third-line: IV cyclophosphamide for severe disease with major organ involvement 1

This positioning reflects that rituximab is level 1B evidence (randomized controlled study) but with strength of recommendation D (expert opinion) for juvenile dermatomyositis 1, while adult data comes primarily from case series and retrospective studies 5, 4, 2.