Population-based national study of relapse-related outcomes in the aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder population

Introduction &amp; Aims<br/>Population-based Danish national study of relapse-related<br/>outcomes in patients with aquaporin-4 antibody seropositive<br/>neuromyelitis optica spectrum disorder (AQP4+ NMOSD).<br/>● Time between initial relapse and initiation of<br/>immunosuppressive maintenance treatment and its<br/>association with the Expanded Disability Status Scale (EDSS).<br/>● Annualized relapse rates.<br/>● Type of initial relapse and the risk of developing more<br/>numerous or fewer attacks.<br/>● Type of relapse and risk of developing other types of<br/>relapses.<br/>● Number and type of relapse and its effect on EDSS.<br/>● Age and its association with relapse severity and subsequent<br/>recovery.<br/>● Association between immunosuppressive maintenance<br/>treatment, relapse treatment, recovery after relapses, and<br/>EDSS.<br/><br/>Methods<br/>● Nationwide retrospective cohort of 66 patients<br/>with AQP4-Ab+ NMOSD.<br/>● Median follow-up time of 99.5 months<br/>(interquartile range: 39-188 months).<br/>● Mixed-effects linear and logistic regression models<br/>were used to examine associations between:<br/>1. Number of relapses and maintenance treatment<br/>and expanded disability status scale (EDSS) scores.<br/>2. Type of relapse and its effect on the EDSS score<br/>changes.<br/>3. Type of initial relapse and risk of developing other<br/>types of relapses and frequency of relapses.<br/>4. Age and relapse severity.<br/>5. Relapse treatment and recovery.<br/><br/>Results<br/>● Longer time before initiation of<br/>immunosuppressive maintenance treatment<br/>was associated with higher EDSS scores at the<br/>last follow-up.<br/>● There was a higher risk of developing optic<br/>neuritis (ON) after transverse myelitis (TM) (OR:<br/>3.21, 95% CI: 1.71-6.02; p &lt;0.001) and, to a<br/>lesser degree, vice versa (OR: 2.91, 95% CI:<br/>1.64-5.17; p &lt;0.001).<br/>● There was also a higher risk of BS relapse after<br/>TM (OR: 2.79, 95% CI: 1.21-6.43; p = 0.016) and,<br/>to a lesser degree, vice versa (OR: 2.40; 95% CI:<br/>1.08-5.31; p = 0.031).<br/>● ON was the only initial relapse type that was<br/>associated with a higher number of relapses at<br/>the last follow-up.<br/>● Not receiving relapse treatment was associated<br/>with higher EDSS changes during the follow-up<br/>period.<br/>● BS relapses were the only type of relapses associated<br/>with a higher EDSS at follow-up.<br/>● Higher age and male sex were associated with more<br/>severe relapses of TM, and male sex was also<br/>associated with worse recovery after ON.<br/>● Peroral methylprednisolone (p = 0.004), intravenous<br/>methylprednisolone (p &lt; 0.001), and methylprednisolone<br/>combined with plasma exchange (p = 0.017) were<br/>associated with better recovery after ON.<br/><br/>Conclusion<br/>Earlier initiation of immuno-<br/>suppressive maintenance<br/>treatment can limit the<br/>accumulation of disability in<br/>NMOSD. Our findings indicate<br/>certain relapse patterns in<br/>NMOSD, which could aid<br/>clinicians in tailoring patient<br/>monitoring and treatment<br/>choices.<br/><br/>Funding<br/>This study was funded by Alexion Pharmaceuticals and the Danish Multiple Society (A39992).