Relationship between Azathioprine metabolites and therapeutic efficacy in Chinese patients with neuromyelitis optica spectrum disorders

Abstract

BackgroundNeuromyelitis optica spectrum disorders (NMOSD) are demyelinating autoimmune diseases in the central nervous system (CNS) that are characterized by a high relapse rate and the presence of anti-aquaporin 4 antibodies (AQP4-IgG) in the serum. Azathioprine (AZA) is a first-line immunomodulatory drug that is widely used for the treatment of patients with NMOSD. However, the efficacy and safety of AZA vary in different individuals.MethodThirty-two patients with NMOSD who regularly took AZA were enrolled in the study at Beijing Tiantan Hospital, Capital Medical University. The efficacy of AZA was evaluated using the expanded disability status scale (EDSS) and the annual relapse rate (ARR). The erythrocyte concentrations of AZA metabolites were detected using an LC-MS/MS method.ResultsThe erythrocyte concentrations of 6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-MMPNs) were 202.03 ± 63.35 pmol/8*108 RBC and 1618.90 ± 1607.06 pmol/8*108 RBC, respectively. After the patients had received AZA therapy for more than one year, the EDSS score decreased from 5.21 ± 0.24 to 2.57 ± 0.33 (p < 0.0001), and the ARR decreased from 1.41 ± 0.23 to 0.36 ± 0.09 (p < 0.0001). The 6-TGN and 6-MMPN levels were significantly different between the non-relapsed and relapsed groups (p < 0.0001, p = 0.006, respectively). A higher ARR was significantly correlated with higher erythrocyte concentrations of 6-TGNs (p < 0.0001) and 6-MMPNs (p = 0.004).ConclusionAZA can reduce the EDSS score and ARR in NMOSD patients. Additionally, the efficacy of AZA is significantly related to the erythrocyte concentrations of 6-TGNs and 6-MMPNs. Within the safe upper limits, a higher concentration of 6-TGNs is associated with better efficacy of AZA.Trial registration number ISRCTN16551495, retrospectively registered on May 22, 2017.

Efficacy for the Annual Relapse Rate after the Immunosuppressive Therapy in Patients Associated with Anti-AQP4 or Anti-MOG Antibody-Positive Optic Neuritis

“…Although there were differences in the background of cases in previous studies, most immunosuppressants still significantly decreased the ARR from 1–3 to 0–1 [ 9 , 16 – 23 ]. Li et al demonstrated that the administration of azathioprine decreased the ARR from 1.41 to 0.36 in 32 cases with NMOSD [ 19 ]. Huang et al demonstrated that mycophenolic acid mofetil for a median duration of 18 months reduced ARR from 1.02 to 0 in 19 cases with NMSOD [ 23 ].…”

<p>Management Strategies of Patients with Neuromyelitis Optica Spectrum Disorder During the COVID-19 Pandemic Era</p>

“…Various immunosuppressive agents including azathioprine (AZA), mycophenolate mofetil (MMF), and cyclophosphamide (CTX), as well as monoclonal antibodies including rituximab (RTX), eculizumab, and tocilizumab have been reported effective in reducing the annualized relapse rate and stabilizing EDSS scores of NMOSD patients. [38][39][40][41][42] The suggested treatment algorithm for the initiation and maintenance of DMTs is outlined in Figure 2.…”