Assessment of disability and disease burden in neuromyelitis optica spectrum disorders in the CIRCLES Cohort

Neuromyelitis optica spectrum disorders (NMOSD) comprise autoimmune diseases imposing substantial disability. We compared an NMOSD-targeted disability assessment of mobility, vision, and self-care domains (individually and composite) with the multiple sclerosis-targeted Expanded Disability Status Scale (EDSS) to assess NMOSD disease burden. An overall cohort (n = 505) and a subset of these patients with an enriched dataset (n = 198) were analyzed from the CIRCLES longitudinal, observational database of patients with AQP4-IgG-seropositive or -seronegative NMOSD in North America. Multinomial modeling was used to identify temporal correlates of disability improvement, stability, and worsening. Prior on-study relapse correlated with worsening mobility (OR, 3.08; 95% CI: 1.61-5.90), vision (OR, 3.99; 95% CI: 2.03-7.86), self-care disability (OR, 1.90; 95% CI: 1.07-3.38), and mean composite index disability (OR, 4.20; 95% CI: 1.71-10.34). Higher vision disability was associated with Black race, shorter time on-study, and AQP4-IgG-seropositive status in patients ≥ 18 years (p < 0.05). Disease onset phenotype and sex correlated with pain interference (p < 0.05). These correlates of NMOSD disability were undetected by EDSS. The CIRCLES real-world experience supports the need for NMOSD-specific disability assessment to improve recognition of disease burden, facilitate proactive clinical management, offer insights into resilience, and inform clinical trial design.