To prospectively study ravulizumab treatment outcomes, enhance knowledge on conventional MRI outcomes, assess for occult disease activity via quantitative imaging metrics, identify serum biomarkers related to disease progression, and explore contemporary social factors that may impact neurological outcomes in people with AQP4-Ab positive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD).

NMOSD is a rare autoimmune central nervous system disorder characterized by AQP4 antibody (AQP4-Ab)-mediated inflammation of the optic nerves and spinal cord. Relapses are unpredictable and often lead to lasting disability. While FDA-approved therapies exist, pivotal trials have lacked detailed neuroimaging assessments, and subclinical disease activity remains poorly understood. Effectiveness of ravulizumab on conventional/non-conventional neuroimaging outcomes also remains underexplored.

This single-center, prospective, observational, 78-week trial includes 35 individuals fulfilling the 2015 International Panel Criteria for AQP4-Ab+ NMOSD. Physical examinations, Expanded Disability Status Scale assessments, conventional/quantitative MRI sequences, and biomarker analysis will be performed at baseline and weeks 13, 26, 52, and 78 post-initiation of ravulizumab treatment. Innovative social and environmental factors influencing health outcomes from participant-reported data and external digital resources will be analyzed throughout.

Enrollment currently consists of 27 subjects (24 female; 10 White; 21 Non-Hispanic; median age at study start=47.15 years (y) (range=22-66y); median disease duration from time of diagnosis=6.09y (0.80-19.01y). To date, 22 subjects have completed week 13, 15 completed week 26, and 9 completed week 52. A total of 72 MRIs have been performed (26 baseline, 46 follow-up). Preliminary findings reveal no evidence of clinical exacerbations, MRI disease progression, or severe adverse reactions to ravulizumab treatment.

Interim findings indicate that ravulizumab is well tolerated and associated with clinical and MRI stability through week 52 in individuals with AQP4-Ab+ NMOSD. As the study progresses, comprehensive evaluation of the biological effects of ravulizumab will provide a deeper understanding of treatment impact.