To investigate the predictors of relapses in seropositive and seronegative neuromyelitis optica spectrum disorder (NMOSD).

NMOSD is a rare central nervous system autoimmune condition where most patients harbour antibodies against aquaporin-4, whilst a minority are seronegative. Previous studies identified some inconsistent results regarding the predictors of relapses in seropositive NMOSD, and a scarcity of knowledge exists about the seronegative subtype. The aim of this study is to characterise and distinguish the relapse risks between seropositive and seronegative NMOSD.

This was a multi-centre, international cohort study using the MSBase database. Relapse risks were assessed as time to first relapse using Cox proportional hazards model and risk of recurrent relapses using Andersen-Gill (AG) model. The covariates included demographic factors (e.g., age, sex and ethnicity), disease duration and treatment exposure. Treatment was assessed as a time-varying covariate and was categorised as high-efficacy and low-moderate efficacy therapies, using multiple sclerosis therapies as reference.

A total of 349 patients were included in the study; 220 seropositive patients followed up for a median of 4.44 years and 129 seronegative patients followed up for a median of 4.95 years. Most patients were on azathioprine (low-moderate efficacy therapy) or rituximab (high-efficacy therapy). In the AG model, exposure to high efficacy therapy was associated with the highest protection against relapses in the seropositive (HR 0.24, CI 0.12-0.47, p<0.001) and seronegative groups (HR 0.24, CI 0.07-0.81, p= 0.02). In the seropositive group, low-moderate efficacy therapy (HR 0.41, CI 0.22-0.75, p= 0.003), male sex (HR 0.47, CI 0.32-0.70, p=<0.001) and longer disease duration (HR 0.96, CI 0.94-0.98, p<0.001) were also protective.

Our results highlight that regardless of antibody status, high efficacy therapy is protective in NMOSD. Whilst further studies are needed to improve our understanding of seronegative NMOSD, this study provides important clinical information about this subtype.