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Research paper
Methotrexate is an alternative to azathioprine in neuromyelitis optica spectrum disorders with aquaporin-4 antibodies
  1. Joanna Kitley1,
  2. Liene Elsone2,
  3. Jithin George1,
  4. Patrick Waters1,
  5. Mark Woodhall1,
  6. Angela Vincent1,
  7. Anu Jacob2,
  8. Maria Isabel Leite1,
  9. Jackie Palace1
  1. 1Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK
  2. 2The Walton Centre for Neurology and Neurosurgery, Liverpool, UK
  1. Correspondence to Jackie Palace, Nuffield Department of Clinical Neurosciences, West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK; jacqueline.palace{at}


Background Neuromyelitis optica (NMO) is a severe autoimmune inflammatory disorder associated with considerable relapse-related disability. Immunosuppression is the mainstay of treatment but many patients do not tolerate first-line immunosuppressive agents, or experience ongoing relapses.

Objective To evaluate the effectiveness and tolerability of methotrexate in aquaporin-4 antibody seropositive NMO spectrum disorders.

Methods Retrospective observational case series of 14 aquaporin-4 antibody positive NMO and NMO spectrum disorder patients treated with methotrexate at two specialist centres within the UK. Annualised relapse rates, Expanded Disability Status Scale scores and tolerability were evaluated.

Results Median duration of treatment with methotrexate was 21.5 months (range 6–28 months) and only three patients were prescribed it first line. Median annualised relapse rate significantly decreased following treatment (0.18 during methotrexate therapy vs 1.39 premethotrexate; p<0.005). On treatment, 43% patients were relapse free, although this increased to 64% when relapses occurring within the first 3 months of treatment or on subtherapeutic doses were excluded. Disability stabilised or improved in 79%. No patients stopped methotrexate due to adverse effects.

Conclusions Methotrexate is a commonly prescribed drug in general practice and when used in NMO it reduces relapse frequency, stabilises disability and is well tolerated, even in patients who have failed one or more other treatments. We would therefore recommend methotrexate as a treatment option in NMO patients who do not tolerate first-line therapy, experience ongoing relapses or in situations where financial constraints limit the available treatment options.


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