Monitoring of Azathioprine Metabolite Concentrations and Cytokine Levels in Neuromyelitis Optica Spectrum Disorder

Treatment tested

• Azathioprine

  Amidophosphoribosyltransferase inhibitor|DNA inhibitor

Inclusion Criteria: All patients with NMOSD met the international consensus diagnostic criteria for NMOSD published in 2015. Before medication, TPMT activity was normal. Exclusion Criteria: Patients with fever, infection, or patients with other autoimmune diseases, uncontrolled malignancies, and other chronic diseases were excluded.

Background: The pathogenesis of NMOSD has been linked to the cytokines interleukins (IL) -6, NOD-, LRR-and pyrin domain-containing 3 (NLRP3) and IL-18 that contribute to development of inflammatory reactionsmay. Although azathioprine (AZA) is efficacious in preventing NMOSD recurrence, it may have adverse effects (AEs) maybe related to the plasma concentrations. Objective: We would monitor the blood concentrations of AZA in NMOSD, and their relationship with cytokines, severity, efficacy, and safety range of the drug. Methods: A total of 53 NMOSD patients were included in the study, which included 20 patients who had received AZA treatment within 1 month, and 16 patients who had received AZA treatment within 6 months, as well as 17 patients who had received AZA treatment at least 12 months. The patient's immunotherapy regimen was low-dose hormone combined with AZA. AZA was started at small doses and added every two weeks after no AEs, namely 50 mg qd for two weeks, 50mg bid for two weeks, and maintained at 50mg tid. The following clinical data were collected: gender, age, clinical symptoms, EDSS score, number of recurrences and AEs, etc. Healthy controls (HC) comprised 10 individuals. AZA metabolite concentrations 6-thioguaninenucleotides (6-TGN) and 6-methylmercaptopurine nucleotides (6-MMPN) were measured by High-performance liquid chromatography (HPLC). Levels of IL-6, NLRP3 and IL-18 were measured by Enzyme-linked immunosorbent assay (ELISA).