Background Neuromyelitis optica spectrum disorder (NMOSD) can be categorised into
aquaporin-4 antibody (AQP4-IgG) NMOSD or seronegative NMOSD. While our knowledge of
AQP4-IgG NMOSD has evolved significantly in the past decade, seronegative NMOSD remains
less understood. This study aimed to evaluate the predictors of relapses and treatment
responses in AQP4-IgG NMOSD and seronegative NMOSD. Methods This was a multicentre,
international, retrospective cohort study using the MSBase registry. Recurrent relapse
risk was assessed using an Andersen-Gill model and risk of first relapse was evaluated
using a Cox proportional hazards model. Covariates that putatively influence relapse
risk included demographic factors, clinical characteristics and immunosuppressive
therapies; the latter was assessed as a time-varying covariate. Results A total of
398 patients (246 AQP4-IgG NMOSD and 152 seronegative NMOSD) were included. The AQP4-IgG
NMOSD and seronegative NMOSD patients did not significantly differ by age at disease
onset, ethnicity or annualised relapse rate. Both low-efficacy and high-efficacy immunosuppressive
therapies were associated with significant reductions in recurrent relapse risk, with
notably greater protection conferred by high-efficacy therapies in both AQP4-IgG NMOSD
(HR 0.27, 95% CI 0.15 to 0.49, p<0.001) and seronegative NMOSD (HR 0.21, 95% CI 0.08
to 0.51, p<0.001). Longer disease duration (HR 0.97, 95% CI 0.95 to 0.99, p<0.001)
and male sex (HR 0.52, 95% CI 0.34 to 0.84, p=0.007) were additional protective variables
in reducing the recurrent relapse risk for the AQP4-IgG NMOSD group. Conclusion Although
further studies are needed to improve our understanding of seronegative NMOSD, our
findings underscore the importance of aggressive treatment with high-efficacy immunotherapies
in both NMOSD subtypes, regardless of serostatus.
