Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder

Mult Scler Relat Disord. 2020 Feb;38:101868. doi: 10.1016/j.msard.2019.101868. Epub 2019 Nov 25.


Background: Aquaporin-4-IgG positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) is an uncommon central nervous system autoimmune disorder. Disease outcomes in AQP4-IgG+NMOSD are typically measured by relapse rate and disability. Using the MSBase, a multi-centre international registry, we aimed to examine the impact immunosuppressive therapies and patient characteristics as predictors of disease outcome measures in AQP4-IgG+NMOSD.

Method: This MSBase cohort study of AQP4-IgG+NMOSD patients examined modifiers of relapse in a multivariable proportional hazards model and expanded disability status score (EDSS) using a mixed effects model.

Results: 206 AQP4-IgG+ patients were included (median follow-up 3.7 years). Age (hazard ratio [HR] = 0.82 per decade, p = 0.001), brainstem onset (HR = 0.45, p = 0.009), azathioprine (HR = 0.46, p<0.001) and mycophenolate mofetil (HR = 0.09, p = 0.012) were associated with a reduced risk of relapse. A greater EDSS was associated with age (β = 0.45 (per decade), p<0.001) and disease duration (β = 0.07 per year, p<0.001). A slower increase in EDSS was associated with azathioprine (β = -0.48, p<0.001), mycophenolate mofetil (β = -0.69, p = 0.04) and rituximab (β = -0.35, p = 0.024).

Interpretation: This study has demonstrated that azathioprine and mycophenolate mofetil reduce the risk of relapses and disability progression is modified by azathioprine, mycophenolate mofetil and rituximab. Age and disease duration were the only patient characteristics that modified the risk of relapse and disability in our cohort.

Keywords: Disability; Immunosuppression; Neuromyelitis optica spectrum disorder; Predictors; Relapses; Therapy.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Age Factors
  • Aquaporin 4 / immunology*
  • Azathioprine / pharmacology
  • Disease Progression*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin G
  • Immunologic Factors / pharmacology*
  • Male
  • Middle Aged
  • Mycophenolic Acid / pharmacology
  • Neuromyelitis Optica* / drug therapy
  • Neuromyelitis Optica* / immunology
  • Neuromyelitis Optica* / physiopathology
  • Outcome Assessment, Health Care*
  • Recurrence
  • Registries*
  • Rituximab / pharmacology
  • Severity of Illness Index*
  • Time Factors


  • AQP4 protein, human
  • Aquaporin 4
  • Immunoglobulin G
  • Immunologic Factors
  • Rituximab
  • Mycophenolic Acid
  • Azathioprine