Objective:

To describe a refractory case of myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD), and the importance of a multimodal immunotherapeutic strategy that targets B cells, T cells, and cytokine pathways in cases resistant to standard treatment.

Background:

MOGAD is a distinct inflammatory demyelinating disorder, separate from multiple sclerosis and neuromyelitis optica. Although some patients remain monophasic, a substantial proportion- especially adults- develop relapsing disease. Although B-cell depletion is often used off-label, relapses can occur despite complete peripheral B-cell suppression. Recent evidence supports a multimodal immune pathogenesis in which MOG-specific CD4+ T cells initiate inflammation in the central nervous system. B cells influence disease activity through antigen presentation and antibody production, while cytokines such as IL-6 and Th17-associated factors drive ongoing inflammation. The constant interaction between these immune pathways accounts for variable treatment responses, supporting a more comprehensive, multimodal approach to therapy.

Design/Methods:

N/A

Results:

A 23-year-old woman presented with right optic neuritis (ON) and was diagnosed with MOGAD. She recovered completely after receiving IV methylprednisolone followed by a taper. Four months later, she developed ON in the left eye, which improved with another course of IV steroids followed by taper and rituximab. One month later, she experienced recurrent left ON and, despite IV methylprednisolone, plasmapheresis, rituximab, and IV immunoglobulin (IVIg), resulting in permanent blindness. Her relapses continued despite undetectable CD19 counts, suggesting the need for therapy beyond B-cell suppression. According to the meta-analysis by Thakolwiboon et al. (2021), relapse-free rates were highest with monthly IVIg (79%) and mycophenolate mofetil (73%) compared with azathioprine (65%) and methotrexate (55%) (p < 0.05). She was started on monthly IVIg and Mycophenolate mofetil for T-cell modulation, resulting in sustained remission.

Conclusions:

This case showcases that refractory MOGAD has an involvement of B cells, T cells, and cytokine-mediated pathways; hence, a combination immunotherapeutic approach may be necessary for refractory cases.