Impact of Age at Onset on Relapse and Disability in AQP4-IgG Neuromyelitis Optica Spectrum Disorder

BACKGROUND AND OBJECTIVES: Previous studies have reported inconsistent findings regarding the impact of age at onset on relapse risk in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), although older disease onset has been linked to more rapid disability accrual. This is in contrast to multiple sclerosis, where advancing age and older onset are associated with reduced relapse activity, allowing for treatment de-escalation or discontinuation in some older patients. The aim of this study was to clarify the influence of age at onset on relapse risk as well as disability accrual in a large, international cohort of patients with NMOSD. METHODS: We conducted a retrospective, multicenter cohort study using the MSBase data registry to evaluate annualized relapse rates (ARRs), time to first relapse, and time to Expanded Disability Status Scale (EDSS) scores of 4 and 6. For inclusion, a diagnosis of AQP4-IgG NMOSD according to the latest iteration of the criteria and availability of the minimum data set were required. Patients were stratified as pediatric onset (<18 years of age), early onset (18-55 years inclusive) or late onset (>55 years of age). Analyses included patients on high-efficacy therapy (HET), those on low-efficacy therapy (LET), and an incident cohort with the first clinical visit within 12 months from disease onset. Predictors of first relapse and EDSS 4/6 thresholds were analyzed using Cox proportional models. RESULTS: < 0.001). Older age was linked to faster disability accumulation. In addition, higher baseline EDSS scores and delayed treatment were independent predictors of future disability. DISCUSSION: Our study demonstrates that while age at onset does not affect relapse risk, older patients experience more rapid disability accrual. These findings underscore the importance of early initiation of effective preventive immunotherapy in all age groups. The primary limitations of this study pertain to its retrospective design and the sole reliance on EDSS for disability assessment.