Rituximab for Myasthenia Gravis
Rituximab is effective for refractory myasthenia gravis, particularly in patients with muscle-specific kinase (MuSK) antibodies, and should be considered when conventional immunosuppressants fail. 1
Evidence for Efficacy
The most recent high-quality evidence from a 2025 Cochrane systematic review demonstrates that rituximab probably results in a large reduction in relapse requiring rescue therapy (45% with rituximab versus 49% with placebo, RR 0.45), though effects on symptom severity remain uncertain due to limited data 1. This represents the strongest available evidence, though it is limited by only two included RCTs with different dosing strategies 1.
Rituximab demonstrates superior efficacy in anti-MuSK positive myasthenia gravis compared to anti-AChR positive disease 2, 3. Multiple studies confirm that patients with MuSK antibodies respond more favorably to rituximab treatment 3.
Clinical Context for Use
Rituximab should be reserved for:
- Refractory generalized myasthenia gravis that has failed conventional immunosuppressants (corticosteroids plus at least one additional agent) 4, 5
- Anti-MuSK antibody positive patients, where rituximab shows particularly strong responses 2, 3
- Patients requiring frequent rescue therapy with IVIG or plasma exchange 4
Dosing Regimens
Two primary dosing strategies exist, though optimal dosing remains unclear 1:
Standard lymphoma protocol: 375 mg/m² IV weekly for 4 consecutive weeks 6, 2
Rheumatology protocol: 1000 mg IV on day 0, repeated on day 15 7, 2
Low-dose protocols (500-1000 mg total) have demonstrated sustained clinical remission with undetectable CD19/CD20 B-cell counts at 12 months, offering a cost-effective alternative particularly relevant for resource-limited settings 5.
Pre-Treatment Requirements
Before initiating rituximab, obtain 7:
- Immunoglobulin levels
- Hepatitis B and C antibody screening
- Latent tuberculosis screening
- Complete blood count with differential
Expected Clinical Response
All patients in a prospective open-label study responded dramatically to rituximab, measured by improvements in manual muscle testing scores, reduced prednisone doses, or decreased frequency of IVIG/plasma exchange 4. Clinical improvement is progressive over 12 weeks 7.
Rituximab results in little to no difference in steroid-sparing effect based on current evidence (RR 1.00), though individual studies show variable results 1.
Safety Profile
Infusion reactions occur in up to 77% during first infusion but are manageable with premedication 7. Monitor complete blood counts at 2-4 month intervals for cytopenias 7.
Critical safety warnings include progressive multifocal leukoencephalopathy and hepatitis B reactivation, necessitating pre-treatment screening 7.
The evidence suggests rituximab may reduce serious adverse events, though certainty is very low (RR 0.81) 1.
Maintenance Strategy
Maintenance dosing every 24 weeks based on clinical response is recommended, though optimal retreatment intervals remain undefined 7. CD19/CD20 levels can guide retreatment decisions, with sustained B-cell depletion correlating with clinical remission 5.
Key Limitations
Current evidence is limited to primarily acetylcholine-receptor antibody positive MG, with serious imprecision in effect estimates 1. Despite widespread off-label use and promising observational data, only two RCTs have been completed, using different dosing strategies that limit direct comparisons 1.