Slowly Progressive Optic Neuritis During Ravulizumab Therapy in a Patient With Aquaporin‐4 Antibody‐Associated Neuromyelitis Optica Spectrum Disorder

ABSTRACT Background Molecular targeted therapies significantly reduce relapse rates in patients with aquaporin‐4 antibody‐positive neuromyelitis optica spectrum disorder (AQP4‐NMOSD). In the Phase 3 CHAMPION‐NMOSD trial of ravulizumab, a C5 inhibitor, no patients experienced a relapse. Case Presentation We report a patient who developed slowly progressive optic neuritis during ravulizumab therapy. A 61‐year‐old Japanese woman first developed left optic neuritis at age 59 and was diagnosed with AQP4‐NMOSD. After acute‐phase treatment, ravulizumab was initiated and prednisolone (PSL) was tapered. Twelve months after onset, she reported minimal blurring in a relatively spared visual field, though no significant changes were detected. Six months later, the blurring worsened, accompanied by declines in visual acuity and critical flicker frequency (CFF). Magnetic resonance imaging (MRI) revealed subtle gadolinium enhancement at the primary lesion, and a relapse was diagnosed. Owing to dependence on high‐dose PSL for relapse prevention, treatment was switched from ravulizumab to inebilizumab, a CD19 inhibitor. Follow‐up MRI subsequently showed diminished gadolinium enhancement, along with improved visual acuity and CFF. This chronic, progressive optic neuritis was diagnosed as an NMOSD relapse during ravulizumab therapy. A breakthrough relapse under C5 inhibition may present with atypical, insidious progression, underscoring the need for careful monitoring. In this patient, CD19‐directed therapy may have suppressed inflammation more effectively, suggesting that pathogenic immune mechanisms may vary among patients. Conclusions This is a rare case of AQP4‐NMOSD presenting with slowly progressive optic neuritis during ravulizumab therapy. Observing patients treated with novel molecular‐targeted drugs may reveal new clinical presentations and underlying pathologies.