From the Research
For myasthenia gravis refractory to eculizumab, consider switching to ravulizumab (Ultomiris) as a potential treatment option, given its similar mechanism but longer half-life, allowing less frequent dosing, as supported by the most recent evidence 1, 2.
Treatment Options
When considering treatment options for myasthenia gravis refractory to eculizumab, several alternatives can be explored:
- Rituximab (375 mg/m² weekly for 4 weeks or 1000 mg on days 1 and 15) depletes B cells and may show effects within 1-3 months 3.
- High-dose cyclophosphamide (50 mg/kg/day for 4 days) can reset the immune system in severe cases.
- Bortezomib (1.3 mg/m² twice weekly for 3 weeks) targets plasma cells and may help antibody-mediated disease.
- Plasma exchange (5-6 exchanges over 10-14 days) or immunoadsorption can provide rapid improvement.
- Thymectomy should be pursued if not already performed, especially in patients with thymoma.
- Combination therapy with conventional immunosuppressants like mycophenolate mofetil (1-1.5g twice daily) or azathioprine (2-3 mg/kg/day) may provide synergistic effects.
Rationale
The rationale behind these treatment options is to target different immunological pathways than complement inhibition, potentially overcoming the mechanisms of eculizumab resistance. Regular monitoring of treatment response using validated MG assessment scales, such as the quantitative myasthenia gravis (QMG) score and the Myasthenia Gravis Activities of Daily Living (MG-ADL) score, is essential to guide therapy adjustments 1, 4.
Recent Evidence
Recent studies have demonstrated the efficacy and safety of eculizumab in patients with refractory generalized myasthenia gravis, including those with a history of rituximab use 4. Additionally, real-world experience has confirmed the safety and effectiveness of eculizumab in reducing myasthenic exacerbations and crisis, and improving clinical outcome measures 1, 2. However, in cases refractory to eculizumab, switching to ravulizumab or exploring other treatment options is necessary to optimize patient outcomes.