Immunotherapies in neuromyelitis optica spectrum disorder: efficacy and predictors of response

J Neurol Neurosurg Psychiatry. 2017 Aug;88(8):639-647. doi: 10.1136/jnnp-2017-315603. Epub 2017 Jun 1.


Objective: To analyse predictors for relapses and number of attacks under different immunotherapies in patients with neuromyelitis optica spectrum disorder (NMOSD).

Design: This is a retrospective cohort study conducted in neurology departments at 21 regional and university hospitals in Germany. Eligible participants were patients with aquaporin-4-antibody-positive or aquaporin-4-antibody-negative NMOSD. Main outcome measures were HRs from Cox proportional hazard regression models adjusted for centre effects, important prognostic factors and repeated treatment episodes.

Results: 265 treatment episodes with a mean duration of 442 days (total of 321 treatment years) in 144 patients (mean age at first attack: 40.9 years, 82.6% female, 86.1% aquaporin-4-antibody-positive) were analysed. 191 attacks occurred during any of the treatments (annual relapse rate=0.60). The most common treatments were rituximab (n=77, 111 patient-years), azathioprine (n=52, 68 patient-years), interferon-β (n=32, 61 patient-years), mitoxantrone (n=34, 32.1 patient-years) and glatiramer acetate (n=17, 10 patient-years). Azathioprine (HR=0.4, 95% CI 0.3 to 0.7, p=0.001) and rituximab (HR=0.6, 95% CI 0.4 to 1.0, p=0.034) reduced the attack risk compared with interferon-β, whereas mitoxantrone and glatiramer acetate did not. Patients who were aquaporin-4-antibody-positive had a higher risk of attacks (HR=2.5, 95% CI 1.3 to 5.1, p=0.009). Every decade of age was associated with a lower risk for attacks (HR=0.8, 95% CI 0.7 to 1.0, p=0.039). A previous attack under the same treatment tended to be predictive for further attacks (HR=1.5, 95% CI 1.0 to 2.4, p=0.065).

Conclusions: Age, antibody status and possibly previous attacks predict further attacks in patients treated for NMOSD. Azathioprine and rituximab are superior to interferon-β.

Keywords: Aquaporin-4 antibody; Azathioprine; Neuromyelitis optica spectrum disorder; Rituximab; Therapy.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adult
  • Aquaporin 4 / immunology
  • Autoantibodies / blood
  • Azathioprine / therapeutic use
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Germany
  • Glatiramer Acetate / therapeutic use
  • Humans
  • Immunotherapy / methods*
  • Interferon-beta / therapeutic use
  • Long-Term Care
  • Male
  • Middle Aged
  • Mitoxantrone / therapeutic use
  • Neuromyelitis Optica / drug therapy*
  • Neuromyelitis Optica / immunology
  • Prognosis
  • Recurrence
  • Registries
  • Retrospective Studies
  • Rituximab / therapeutic use
  • Treatment Outcome


  • AQP4 protein, human
  • Aquaporin 4
  • Autoantibodies
  • Rituximab
  • Glatiramer Acetate
  • Interferon-beta
  • Mitoxantrone
  • Azathioprine