Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune inflammatory disease of the central nervous system, resulting in astrocytopathy and secondary demyelination (Wingerchuk et al., 2015; Contentti and Correale, 2021). This condition is often mediated by aquaporin-4 IgG antibodies (AQ4-IgG), however approximately 20% are seronegative patients (Wingerchuk et al., 2015). The worldwide prevalence is around 0.5–1/1000 people and NMOSD is more frequent in females and Black or Asian populations (Papp et al., 2021).

The effectiveness of Azathioprine (AZA) and mycophenolate mofetil (MMF) has been reported in observational studies: 55.9% of patients with AZA and 50–73% with MMF were free from relapse, during 15.5 to 19.5 months of follow-up (Zhang et al., 2022; Huang et al., 2018), and 69% of patients presented no disability accumulation along 4.6 years of follow-up with AZA (Bichuetti et al., 2019). However, in a randomized clinical trial from Iran of 68 patients, the patients in the rituximab group presented with fewer relapses compared to AZA (21.2% and 45.7%, respectively) (Nikoo et al., 2017). Another randomized clinical trial, from China, demonstrated greater efficacy of tocilizumab over AZA in patients with frequent relapses (Zhang et al., 2020).

In studies from South Korea and China, patients who had severe pre-treatment relapses were more likely to have an unsatisfactory response to traditional immunosuppressants (AZA and MMF) (Zhang et al., 2022; Kim et al., 2017). It is unclear if these findings apply to other populations. For instance, this finding was not reproduced in a German study in which no relapse predictors were identified (Stellmann et al., 2017).

The optimal starting therapy for NMOSD remains unclear. AZA and MMF continue to be widely used in resource-limited countries and are effective in a proportion of patients (Zhang et al., 2022; Huang et al., 2018; Bichuetti et al., 2019). A priori knowledge of a patient's likelihood to respond favorably or unfavorably to AZA or MMF could help personalize and rationalize high-cost treatments. This study aimed to establish predictors of AZA or MMF response and identify patients in whom high-efficacy drugs should be required from the outset.