title: Long-term follow-up of patients with neuromyelitis optica after repeated therapy with rituximab.
abstract: 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.
  
  
  CONCLUSIONS
  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.
  
  
  METHODS
  This study provides Class IV evidence that repeated doses of rituximab result in stabilization in most patients.
authors.affiliation: Institute of Clinical Neuroimmunology, Ludwig Maximilians University, D-81377 Munich, Germany. hannah.pellkofer@med.uni-muenchen.de
authors.forename: H L
authors.initials: HL
authors.lastname: Pellkofer
authors.forename: M
authors.initials: M
authors.lastname: Krumbholz
authors.forename: A
authors.initials: A
authors.lastname: Berthele
authors.forename: B
authors.initials: B
authors.lastname: Hemmer
authors.forename: L A
authors.initials: LA
authors.lastname: Gerdes
authors.forename: J
authors.initials: J
authors.lastname: Havla
authors.forename: R
authors.initials: R
authors.lastname: Bittner
authors.forename: M
authors.initials: M
authors.lastname: Canis
authors.forename: E
authors.initials: E
authors.lastname: Meinl
authors.forename: R
authors.initials: R
authors.lastname: Hohlfeld
authors.forename: T
authors.initials: T
authors.lastname: Kuempfel
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects; D051401:Aquaporin 4 / Q000276:immunology; D053264:B-Cell Activating Factor / Q000097:blood; D001402:B-Lymphocytes; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects; D007958:Leukocyte Count; D008137:Longitudinal Studies; D008297:Male; D009471:Neuromyelitis Optica / Q000188:drug therapy* / Q000503:physiopathology; D009994:Osmolar Concentration; D011446:Prospective Studies; D000069283:Rituximab; D016896:Treatment Outcome; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000097:blood
chemical_list: C496030:AQP4 protein, human; D000906:Antibodies; D058846:Antibodies, Monoclonal, Murine-Derived; D051401:Aquaporin 4; D053264:B-Cell Activating Factor; D007155:Immunologic Factors; C505719:TNFSF13B protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D000069283:Rituximab