Case Report: Sequential FcRn blockade and B-cell depletion for treatment-refractory relapsing autoimmune...

Refractory autoimmune encephalitis (AE), particularly in patients experiencing recurrent relapses, presents significant therapeutic challenges and underscores the urgent need for innovative treatment strategies. Emerging evidence shows efgartigimod (EFG) rapidly clears pathogenic antibodies (days), while rituximab (RTX) suppresses new antibody production (weeks-months). Their synergistic temporal effects provide a rationale for exploring sequential EFG-RTX as a treatment strategy. Here, we describe the preliminary clinical outcomes observed in three patients with refractory AE who received this sequential regimen.

The cohort included three refractory cases: A 30-year-old female patient diagnosed with anti-glutamate decarboxylase 65 encephalitis, who had experienced three disease relapses and presented with refractory epilepsy, a 54-year-old female with relapsed anti-leucine-rich glioma-inactivated protein 1 encephalitis showing progressive cognitive decline and psychiatric symptoms, and a 19-year-old female with relapsed anti-N-methyl-D-aspartate receptor encephalitis, characterized by severe cognitive dysfunction, psychiatric disturbances, depressed consciousness, and central hypoventilation. All patients had demonstrated resistance to both first-line immunotherapies and second-line agents including cyclophosphamide. Notably, administration of EFG yielded substantial clinical improvement in all cases, with sustained remission achieved following subsequent RTX and no evidence of disease relapse.

In this small case series, sequential EFG-RTX therapy was associated with substantial clinical improvement and sustained remission in three patients with highly refractory, relapsing AE. These preliminary observations suggest that this synergistic approach may represent a viable therapeutic option for similar difficult-to-treat cases and warrants further investigation in larger, controlled studies.