Relationship between Azathioprine metabolites and therapeutic efficacy in Chinese patients with neuromyelitis optica spectrum disorders
Abstract Background Neuromyelitis 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 immu...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2017-07-01
|
| Series: | BMC Neurology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12883-017-0903-5 |
| _version_ | 1819013230696071168 |
|---|---|
| author | Xindi Li Shenghui Mei Xiaoqing Gong Heng Zhou Li Yang Anna Zhou Yonghong Liu Xingang Li Zhigang Zhao Xinghu Zhang |
| author_facet | Xindi Li Shenghui Mei Xiaoqing Gong Heng Zhou Li Yang Anna Zhou Yonghong Liu Xingang Li Zhigang Zhao Xinghu Zhang |
| author_sort | Xindi Li |
| collection | DOAJ |
| description | Abstract Background Neuromyelitis 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. Method Thirty-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. Results The 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). Conclusion AZA 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. |
| first_indexed | 2024-12-21T01:56:39Z |
| format | Article |
| id | doaj.art-f87dd5dc451a457faa59e2cb3faa9049 |
| institution | Directory Open Access Journal |
| issn | 1471-2377 |
| language | English |
| last_indexed | 2024-12-21T01:56:39Z |
| publishDate | 2017-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neurology |
| spelling | doaj.art-f87dd5dc451a457faa59e2cb3faa90492022-12-21T19:19:46ZengBMCBMC Neurology1471-23772017-07-011711810.1186/s12883-017-0903-5Relationship between Azathioprine metabolites and therapeutic efficacy in Chinese patients with neuromyelitis optica spectrum disordersXindi Li0Shenghui Mei1Xiaoqing Gong2Heng Zhou3Li Yang4Anna Zhou5Yonghong Liu6Xingang Li7Zhigang Zhao8Xinghu Zhang9Neuroinfection and Neuroimmunology Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Pharmacy, Beijing Tiantan Hospital, Capital Medical UniversityNeuroinfection and Neuroimmunology Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical UniversityNeuroinfection and Neuroimmunology Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Pharmacy, Beijing Tiantan Hospital, Capital Medical UniversityNeuroinfection and Neuroimmunology Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical UniversityNeuroinfection and Neuroimmunology Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Pharmacy, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Pharmacy, Beijing Tiantan Hospital, Capital Medical UniversityNeuroinfection and Neuroimmunology Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical UniversityAbstract Background Neuromyelitis 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. Method Thirty-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. Results The 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). Conclusion AZA 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.http://link.springer.com/article/10.1186/s12883-017-0903-5Neuromyelitis optica spectrum disorders (NMOSD)Azathioprine (AZA)Thiopurine S-methyltransferase (TPMT)6-thioguanine nucleotides (6-TGNs)6-methylmercaptopurine nucleotides (6-MMPNs) |
| spellingShingle | Xindi Li Shenghui Mei Xiaoqing Gong Heng Zhou Li Yang Anna Zhou Yonghong Liu Xingang Li Zhigang Zhao Xinghu Zhang Relationship between Azathioprine metabolites and therapeutic efficacy in Chinese patients with neuromyelitis optica spectrum disorders BMC Neurology Neuromyelitis optica spectrum disorders (NMOSD) Azathioprine (AZA) Thiopurine S-methyltransferase (TPMT) 6-thioguanine nucleotides (6-TGNs) 6-methylmercaptopurine nucleotides (6-MMPNs) |
| title | Relationship between Azathioprine metabolites and therapeutic efficacy in Chinese patients with neuromyelitis optica spectrum disorders |
| title_full | Relationship between Azathioprine metabolites and therapeutic efficacy in Chinese patients with neuromyelitis optica spectrum disorders |
| title_fullStr | Relationship between Azathioprine metabolites and therapeutic efficacy in Chinese patients with neuromyelitis optica spectrum disorders |
| title_full_unstemmed | Relationship between Azathioprine metabolites and therapeutic efficacy in Chinese patients with neuromyelitis optica spectrum disorders |
| title_short | Relationship between Azathioprine metabolites and therapeutic efficacy in Chinese patients with neuromyelitis optica spectrum disorders |
| title_sort | relationship between azathioprine metabolites and therapeutic efficacy in chinese patients with neuromyelitis optica spectrum disorders |
| topic | Neuromyelitis optica spectrum disorders (NMOSD) Azathioprine (AZA) Thiopurine S-methyltransferase (TPMT) 6-thioguanine nucleotides (6-TGNs) 6-methylmercaptopurine nucleotides (6-MMPNs) |
| url | http://link.springer.com/article/10.1186/s12883-017-0903-5 |
| work_keys_str_mv | AT xindili relationshipbetweenazathioprinemetabolitesandtherapeuticefficacyinchinesepatientswithneuromyelitisopticaspectrumdisorders AT shenghuimei relationshipbetweenazathioprinemetabolitesandtherapeuticefficacyinchinesepatientswithneuromyelitisopticaspectrumdisorders AT xiaoqinggong relationshipbetweenazathioprinemetabolitesandtherapeuticefficacyinchinesepatientswithneuromyelitisopticaspectrumdisorders AT hengzhou relationshipbetweenazathioprinemetabolitesandtherapeuticefficacyinchinesepatientswithneuromyelitisopticaspectrumdisorders AT liyang relationshipbetweenazathioprinemetabolitesandtherapeuticefficacyinchinesepatientswithneuromyelitisopticaspectrumdisorders AT annazhou relationshipbetweenazathioprinemetabolitesandtherapeuticefficacyinchinesepatientswithneuromyelitisopticaspectrumdisorders AT yonghongliu relationshipbetweenazathioprinemetabolitesandtherapeuticefficacyinchinesepatientswithneuromyelitisopticaspectrumdisorders AT xingangli relationshipbetweenazathioprinemetabolitesandtherapeuticefficacyinchinesepatientswithneuromyelitisopticaspectrumdisorders AT zhigangzhao relationshipbetweenazathioprinemetabolitesandtherapeuticefficacyinchinesepatientswithneuromyelitisopticaspectrumdisorders AT xinghuzhang relationshipbetweenazathioprinemetabolitesandtherapeuticefficacyinchinesepatientswithneuromyelitisopticaspectrumdisorders |