Relationship between Azathioprine metabolites and therapeutic efficacy in Chinese patients with neuromyelitis optica spectrum disordersReportar como inadecuado




Relationship between Azathioprine metabolites and therapeutic efficacy in Chinese patients with neuromyelitis optica spectrum disorders - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Neurology

, 17:130

Demyelinating diseases

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*10 RBC and 1618.90 ± 1607.06 pmol-8*10 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 numberISRCTN16551495, retrospectively registered on May 22, 2017.

KeywordsNeuromyelitis optica spectrum disorders NMOSD Azathioprine AZA Thiopurine S-methyltransferase TPMT 6-thioguanine nucleotides 6-TGNs 6-methylmercaptopurine nucleotides 6-MMPNs Abbreviations6-MMPNs6-methylmercaptopurine nucleotides

6-MP6-mercaptopurine

6-TG6-thioguanine

6-TGNs6-thioguanine nucleotides

ALLAcute lymphoblastic leukemia

AQP4-IgGAnti-aquaporin 4 antibodies

ARRAnnual relapse rates

AZAAzathioprine

CNSCentral nervous system

EDSSExpanded disability status scale

HGPRTHypoxanthine-guanine phosphoribosyltransferase

HWEHardy-Weinberg equilibrium

MAFMinor allele frequency

NMOSDNeuromyelitis optica spectrum disorders

PDNSPurine de novo synthesis

SDStandard deviation

SLC28ASolute carrier family 28

SLC29ASolute carrier family 29

SNPsSingle nucleotide polymorphisms

TPMTThiopurine S-methyltransferase

TPNsThiopurine nucleotides

Download fulltext PDF



Autor: Xindi Li - Shenghui Mei - Xiaoqing Gong - Heng Zhou - Li Yang - Anna Zhou - Yonghong Liu - Xingang Li - Zhigang Zhao - Xi

Fuente: https://link.springer.com/



DESCARGAR PDF




Documentos relacionados