title: Long-term efficacy, tolerability and retention rate of azathioprine in 103 aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder patients: a multicentre retrospective observational study from the UK.
abstract: BACKGROUND
  Azathioprine (AZA) is a common immunosuppressive drug used for relapse prevention in neuromyelitis optica (NMO).
  
  
  OBJECTIVE
  The objective of this paper is to assess efficacy, tolerability and retention of AZA in a large NMO cohort.
  
  
  METHODS
  We conducted a retrospective review of medical records of 103 aquaporin-4 antibody-positive NMO and NMO spectrum disorder (NMOSD) patients treated with AZA.
  
  
  RESULTS
  This is the largest reported cohort of AQP4-Ab positive patients treated with AZA. Eighty-nine per cent (n = 92) had reduction in median annualised relapse rates from 1.5 (IQR 0.6-4.0) to 0 (IQR 0-0.27, p < 0.00005) with treatment. Sixty-one per cent (n = 63) remained relapse free at a median follow-up of 18 months. Neurological function improved or stabilised in 78%. At last follow-up, treatment was discontinued in 46% (n = 47). Of these, 62% (n = 29) were because of side effects, 19% (n = 9) because of death, 15% (n = 7) because of ongoing disease activity, and 2% (n = 1) because of pregnancy. Using Kaplan-Meyer curves, we estimate that 73%, 58%, 47% and 33% of patients will remain on AZA for longer than one, three, five and 10 years, respectively, after initiation of treatment.
  
  
  CONCLUSIONS
  AZA is a modestly effective treatment for NMO. However, many patients discontinue AZA over time and this seems to reflect poor tolerability more than lack of efficacy.
authors.affiliation: The Walton Centre NHS Foundation Trust, UK.
authors.forename: Liene
authors.initials: L
authors.lastname: Elsone
authors.affiliation: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kitley
authors.affiliation: Cardiff and Vale University Health Board, University Hospital of Wales, UK.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Luppe
authors.affiliation: University of Liverpool, CRUK Liverpool Cancer Trials Unit, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lythgoe
authors.affiliation: The Walton Centre NHS Foundation Trust, UK.
authors.forename: Kerry
authors.initials: K
authors.lastname: Mutch
authors.affiliation: Queen Elizabeth Neuroscience Centre, University Hospitals of Birmingham, UK.
authors.forename: Saiju
authors.initials: S
authors.lastname: Jacob
authors.affiliation: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Brown
authors.affiliation: Royal Liverpool University Hospital, UK.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Moss
authors.affiliation: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, UK.
authors.forename: Benjamin
authors.initials: B
authors.lastname: McNeillis
authors.affiliation: The Walton Centre NHS Foundation Trust, UK.
authors.forename: Yee Yen
authors.initials: YY
authors.lastname: Goh
authors.affiliation: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, UK.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Leite
authors.affiliation: Cardiff and Vale University Health Board, University Hospital of Wales, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Robertson
authors.affiliation: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, UK.
authors.forename: Jackie
authors.initials: J
authors.lastname: Palace
authors.affiliation: The Walton Centre NHS Foundation Trust, UK anu.jacob@thewaltoncentre.nhs.uk.
authors.forename: Anu
authors.initials: A
authors.lastname: Jacob
mesh_terms: D000328:Adult; D000368:Aged; D051401:Aquaporin 4 / Q000276:immunology*; D001379:Azathioprine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000188:drug therapy* / Q000276:immunology; D012008:Recurrence; D012189:Retrospective Studies; D013995:Time; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D007166:Immunosuppressive Agents; D001379:Azathioprine
keywords: NMO; Neuromyelitis optica; aquaporin-4; azathioprine; retention; tolerability