Therapeutic Response in Pediatric Neuromyelitis Optica Spectrum Disorder

Background and Objective Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune condition, which can lead to significant disability, and up to 3%–5% of the cases have a pediatric onset. There are limited studies to guide physicians in disease-modifying treatment (DMT) choices for children with NMOSD. Methods This retrospective cohort study evaluated children with NMOSD cases followed at 12 clinics in the US Network of Pediatric MS Centers. Cases were classified as aquaporin-4 antibody positive (AQP4+) and double seronegative (DS) when negative for AQP4+ and for myelin oligodendrocyte glycoprotein (MOG) antibody. The effect of initial DMTs including rituximab, mycophenolate, azathioprine, and IV immunoglobulin (IVIg) on the annualized relapse rate (ARR) was assessed by negative binomial regression. Time to disability progression (EDSS score increase ≥1.0 point) was modeled with a Cox proportional-hazards model. Results A total of 91 children with NMOSD were identified: 77 AQP4+ and 14 DS (85.7% females; 43.2% White and 46.6% African American). Eighty-one patients were started on a DMT, and 10 were treatment naive at the time of the analysis. The ARR calculated in all serogroups was 0.25 (95% CI 0.13–0.49) for rituximab, 0.33 (95% CI 0.19–0.58) for mycophenolate, 0.40 (95% CI 0.13–1.24) for azathioprine, and 0.54 (95% CI 0.28–1.04) for IVIg. The ARR in the AQP4+ subgroup was 0.28 (95% CI 0.14–0.55) for rituximab, 0.39 (95% CI 0.21–0.70) for mycophenolate, 0.41 (95% CI 0.13–1.29) for azathioprine, and 0.54 (95% CI 0.23–1.26) for IVIg. The ARR in the treatment-naive group was 0.97 (95% CI 0.58–1.60) in all serogroups and 0.91 (95% CI 0.53–1.56) in the AQP4+ subgroup. None of the initial DMT had a statistically significant effect on EDSS progression. Discussion The use of DMTs, particularly rituximab, is associated with a lowered annualized relapse rate in children with NMOSD AQP4+. Classification of Evidence This study provides Class IV evidence that use of disease-modifying treatments is associated with a lowered annualized relapse rate in children with NMOSD AQP4+.