Failure of natalizumab to prevent relapses in neuromyelitis optica

Arch Neurol. 2012 Feb;69(2):239-45. doi: 10.1001/archneurol.2011.216.


Objective: To describe first experiences with the integrin inhibitor natalizumab, given to patients with suspected relapsing-remitting multiple sclerosis (MS) who were later diagnosed with aquaporin 4-positive neuromyelitis optica (NMO).

Design: Retrospective case series.

Setting: Neurology departments at tertiary referral centers in Germany.

Patients: Patients with NMO who tested positive for antibodies to aquaporin 4.

Intervention: Treatment with natalizumab.

Main outcome measures: Relapses and accumulation of disability.

Results: We identified 5 patients (4 female; median age, 45 years) who were initially diagnosed with MS and treated with natalizumab before diagnosis of NMO was established. Natalizumab was given as escalation therapy after failure of first- or second-line immunomodulatory therapies for MS. During natalizumab therapy (median duration, 8 infusions; range, 2-11 infusions), all 5 patients displayed persisting disease activity; a total of 9 relapses occurred (median duration to relapse, 120 days; range, 45-230 days) after the start of treatment. Four patients had an accumulation of disability and 1 patient died 2 months after cessation of natalizumab treatment.

Conclusions: Our results suggest that natalizumab fails to control disease activity in patients with NMO. Neuromyelitis optica should be considered as a differential diagnosis in patients with suspected MS who are unresponsive to natalizumab therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Aquaporin 4 / blood
  • Aquaporin 4 / immunology
  • Autoantibodies / analysis
  • Disability Evaluation
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / complications
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy
  • Natalizumab
  • Neuromyelitis Optica / prevention & control*
  • Secondary Prevention
  • Treatment Failure
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Aquaporin 4
  • Autoantibodies
  • Natalizumab