Long-term follow-up of patients with neuromyelitis optica after repeated therapy with rituximab

Neurology. 2011 Apr 12;76(15):1310-5. doi: 10.1212/WNL.0b013e3182152881.


Background: Neuromyelitis optica (NMO) is a severe autoimmune disease targeting optic nerves and spinal cord. The monoclonal anti-CD20 B-cell antibody rituximab is an emerging therapeutic option in NMO. However, neither long-term efficacy or safety of rituximab, nor the correlation between B-cell counts, B-cell fostering cytokines, aquaporin-4 antibodies (AQP4-ab), and disease activity in NMO, have been investigated prospectively.

Methods: We performed a prospective long-term cohort study of 10 patients with NMO who were treated up to 5 times with rituximab as a second-line therapy. Clinical examinations, B-cell counts, and serum concentrations of BAFF (B-cell activating factor of the TNF family; also called TNFSF13b), APRIL (a proliferation-inducing ligand; also called TNFSF13), AQP4-ab, and immunoglobulin levels were measured every 3 months.

Results: Repeated treatment with rituximab led to sustained clinical stabilization in most patients with NMO. Disease activity correlated with B-cell depletion, but not clearly with AQP4-ab or levels of APRIL. BAFF levels increased after application of rituximab and indicated persisting efficacy of the drug but did not correlate with disease activity. Overall, rituximab was well-tolerated even after up to 5 consecutive treatment courses; however, we observed several severe adverse reactions.

Conclusion: Our data indicate that long-term therapy with rituximab is effective in NMO as a second-line therapy and has an acceptable safety profile. Retreatment with rituximab should be applied before reappearance of circulating B cells.

Classification of evidence: This study provides Class IV evidence that repeated doses of rituximab result in stabilization in most patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies / blood
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage*
  • Antibodies, Monoclonal, Murine-Derived / adverse effects
  • Aquaporin 4 / immunology
  • B-Cell Activating Factor / blood
  • B-Lymphocytes
  • Cohort Studies
  • Drug Administration Schedule
  • Female
  • Humans
  • Immunologic Factors / administration & dosage*
  • Immunologic Factors / adverse effects
  • Leukocyte Count
  • Longitudinal Studies
  • Male
  • Neuromyelitis Optica / drug therapy*
  • Neuromyelitis Optica / physiopathology
  • Osmolar Concentration
  • Prospective Studies
  • Rituximab
  • Treatment Outcome
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / blood


  • AQP4 protein, human
  • Antibodies
  • Antibodies, Monoclonal, Murine-Derived
  • Aquaporin 4
  • B-Cell Activating Factor
  • Immunologic Factors
  • TNFSF13B protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • Rituximab