Azathioprine metabolite levels and outcomes during pregnancies with rheumatic disease.
Azathioprine metabolite levels and outcomes during pregnancies with rheumatic disease.
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DOI：
10.1136/lupus-2023-001036
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发表时间：
2024-01-03
影响因子：
3.9
通讯作者：
中科院分区：
文献类型：
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作者：
尽管在妊娠期间广泛使用硫唑嘌呤（AZA），但没有研究评估妊娠对AZA代谢物6-硫鸟嘌呤核苷酸（6-TGN）和6-甲巯基嘌呤核苷酸（6-MMPN）在风湿性疾病中分布的影响。本研究描述了风湿性疾病妇女在整个妊娠期间AZA代谢物浓度的变化，并探讨了代谢物浓度、母体疾病活动和新生儿结局之间的关系。纳入了来自单个中心的风湿性疾病患者，这些患者在妊娠前接受了AZA处方，并且在妊娠期间采集了≥1份血样（5/2016 - 4/2022）。商业实验室定量AZA代谢物浓度。6-MMPN的安全上限为>5700 pmol/8×108 RBC。6-TGN的治疗靶点为≥159 pmol/8×108 RBC。重复相关性测量用于评估代谢物浓度与妊娠持续时间之间的关系，以及6-TGN浓度与SLE医生总体评估（PGA）之间的关系。采用线性回归分析妊娠平均6-TGN与新生儿出生时孕周的关系。包括35名妇女的37例妊娠，108份血清样本。剂量调整后的6-TGN浓度在整个妊娠期和围产期没有显著差异，而6-MMPN浓度在妊娠期间似乎更高。6-MMPN高于5700 pmol/8×108 RBC时，未观察到转氨酶升高或胆汁淤积。代谢物浓度与AZA总剂量、体重剂量和TPMT表型相关。在达到治疗范围内平均6-TGN的SLE孕妇中，我们观察到PGA无显著降低，新生儿出生时胎龄增加。在这项探索性研究中，我们没有观察到整个妊娠期和围产期6-TGN浓度的系统性变化，而6-MMPN浓度在妊娠期间较高。监测妊娠期AZA代谢物浓度是一种潜在的工具，可以识别药物不依从性以及6-MMPN高的患者，其中剂量调整或密切的实验室监测可以优化安全性。
Despite widespread use of azathioprine (AZA) during pregnancy, no studies evaluated the impact of pregnancy on AZA metabolites 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine nucleotide (6-MMPN) disposition in rheumatic diseases. This study characterises changes in AZA metabolite concentrations throughout pregnancy in women with rheumatic disease and explores relationships between metabolite concentrations, maternal disease activity, and neonatal outcomes. Patients with rheumatic disease from a single centre prescribed AZA prior to pregnancy and ≥1 blood sample during pregnancy (5/2016 to 4/2022) were included. Commercial laboratories quantified AZA metabolite concentrations. The upper safety limit for 6-MMPN was >5700 pmol/8×108 RBC. The therapeutic target for 6-TGN was ≥159 pmol/8×108 RBC. Repeated correlation measures were used to evaluate the relationship between metabolite concentrations and pregnancy duration, and the relationship between 6-TGN concentration and SLE Physician Global Assessment (PGA). The relationship between pregnancy average 6-TGN and neonatal gestational age at birth was analysed using linear regression. Thirty-seven pregnancies in 35 women with 108 serum samples were included. There was no significant difference in dose-adjusted 6-TGN concentrations across pregnancy and peripartum, whereas 6-MMPN concentrations appeared higher during pregnancy. No elevated transaminases or cholestasis were observed concurrently with 6-MMPN above 5700 pmol/8×108 RBC. Metabolite concentrations were related to total AZA dosage, weight-based dosage and TPMT phenotype. In pregnant women with SLE achieving average 6-TGN in the therapeutic range, we observed a non-significant reduction in PGA and increase in neonatal gestational age at birth. In this exploratory study, we did not observe systematic changes in 6-TGN concentrations throughout pregnancy and peripartum, whereas 6-MMPN concentrations were higher during pregnancy. Monitoring AZA metabolite concentrations in pregnancy is a potential tool to identify medication non-adherence as well as patients with high 6-MMPN in whom dosage adjustment or close laboratory monitoring may optimise safety.
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影响因子：
3.9
作者：
Balevic SJ;Weiner D;Clowse MEB;Eudy AM;Maharaj AR;Hornik CP;Cohen-Wolkowiez M;Gonzalez D
通讯作者：
Gonzalez D
影响因子：
2.3
作者：
Clowse, Megan E. B.
通讯作者：
Clowse, Megan E. B.
影响因子：
--
作者：
Costedoat-Chalumeau, Nathalie;Amoura, Zahir;Piette, Jean-Charles
通讯作者：
Piette, Jean-Charles
影响因子：
--
作者：
PETRI, M;GENOVESE, M;HOCHBERG, M
通讯作者：
HOCHBERG, M
影响因子：
3.8
作者：
Bakdash JZ;Marusich LR
通讯作者：
Marusich LR