To assess the relationship between disease phenotypes and treatment change in patients with neuromyelitis optica spectrum disorder (NMOSD) participating in the CIRCLES study from 2013 to 2020.

NMOSD is a rare autoimmune condition with heterogeneous disease phenotype. Disease phenotypes are hypothesized to impact change in maintenance treatment. Real-world data were analyzed seeking correlates of propensity for treatment change in patients with NMOSD.

Of 542 patients studied, cumulatively 131 patients (24.2%) changed maintenance treatment regimen.  In a multivariate model, variables associated with significantly increased treatment change were: anti-AQP4-IgG seronegativity (HR = 1.71; p=0.014); disease duration < 1 year vs. > 5 years (HR = 1.94, p=0.012); baseline ARR  >0.75 (HR = 3.05, p<0.001) or 0.25-0.75 (HR = 1.77, p=0.027; vs.  ARR < 0.25); disease onset phenotype as brain only vs. any transverse myelitis (HR = 2.41, p=0.008) and autoimmune disease comorbidity (HR = 1.72, p=0.004). Gender, race/ethnicity or age at NMOSD onset were not significant correlates of treatment change.

In CIRCLES, anti-AQP4-IgG seronegativity, disease onset phenotype involving brain only, shorter disease duration, and autoimmune disease comorbidity significantly correlated with treatment change probability. These results suggest potential clinical drivers or predictors of treatment change in patients as the field evolves from off-label, non-specific immunosuppressants to targeted biologics in a new era of approved therapies. In turn, such findings may advance the optimal use of therapeutic regimens to minimize disease burden and maximize quality of life in patients with NMOSD.