Methotrexate is an alternative to azathioprine in neuromyelitis optica spectrum disorders with aquaporin-4 antibodies.

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.