Initiating Immunosuppressants After Pulse Therapy in Autoimmune Encephalitis

Introduction to Immunosuppressant Therapy

The American Academy of Neurology recommends initiating second-line immunosuppressants (rituximab or cyclophosphamide) if there is no significant clinical, radiological, or electrophysiological response after 2-4 weeks of optimized first-line therapy 1, 2

The absence of clinical improvement after 2-4 weeks of treatment with high-dose corticosteroids, intravenous immunoglobulin (IVIG), or plasmapheresis (PLEX) is a criterion for therapeutic failure 1, 2
Failure to respond to more than one first-line agent is the preferred criterion for 50% of specialists before adding second-line therapy 3
Progressive clinical deterioration despite adequate first-line therapy, especially in patients with hemodynamic compromise or severe dysfunction, is another criterion for therapeutic failure 4, 2

Rituximab is the preferred second-line agent (chosen by 80% of specialists) for antibody-mediated autoimmune encephalitis, particularly when the antibodies are unknown or targeted against neuronal surface antigens 3, 1
Consider rituximab especially in cases with anti-NMDAR, anti-LGI1, or anti-CASPR2 antibodies that do not respond to first-line therapy 4, 1

Cyclophosphamide should be considered for T-cell mediated autoimmunity, particularly in classical paraneoplastic encephalitis 1, 2
It is an alternative to rituximab when there is suspicion of predominant cellular pathogenic mechanisms 3, 1

Administer first-line therapy: methylprednisolone IV (1-2 mg/kg/day or pulse therapy 1g/day for 3-5 days) 1, 2
Add IVIG (0.4 g/kg/day for 5 days) or PLEX (5-10 sessions on alternate days) if there is severe presentation or contraindications to steroids 1, 5, 2

If there is clinical improvement: continue with bridge therapy (gradual tapering of oral prednisone, monthly IVIG, or monthly methylprednisolone IV) 5
If there is no improvement or minimal improvement: proceed to second-line therapy 1, 2

For known or unknown neuronal surface antibodies: rituximab 375 mg/m² IV weekly for 4 doses or 1g on days 1 and 15 3, 1
For paraneoplastic encephalitis or suspected T-cell mediated mechanism: cyclophosphamide 0.5-1 g/m² every 3 weeks for 4-6 months 6, 1

Permanently discontinue the immune checkpoint inhibitor if there is related autoimmune encephalitis 1, 2
Initiate methylprednisolone at a pulse dose (1g/day) and consider IVIG or PLEX if there is no improvement or worsening after 3 days 4

Do not wait for antibody test results to initiate immunotherapy; delayed treatment worsens outcomes 2
Do not underestimate the need for early escalation: 32% of specialists add second-line agents after failure of only one first-line agent 3
Do not neglect oncological screening: failure to identify paraneoplastic causes can compromise treatment 2
Avoid monotherapy with steroids in severe cases: consider combination therapy (steroids + IVIG or steroids + PLEX) from the start in severe presentations 5, 2