Hydroxychloroquine Levels throughout Pregnancies Complicated by Rheumatic Disease: Implications for Maternal and Neonatal Outcomes.
Hydroxychloroquine Levels throughout Pregnancies Complicated by Rheumatic Disease: Implications for Maternal and Neonatal Outcomes.
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DOI：
10.3899/jrheum.180158
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发表时间：
2019-01
期刊：
影响因子：
--
通讯作者：
Clowse MEB
中科院分区：
文献类型：
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作者：
Balevic SJ;Cohen-Wolkowiez M;Eudy AM;Green TP;Schanberg LE;Clowse MEB
患有活动性风湿病的妇女怀孕往往导致新生儿预后不良。羟氯喹（HCQ）减少疾病活动和耀斑，然而，妊娠引起显著的生理变化，可能改变HCQ水平并导致治疗失败。因此，我们的目的是评估妊娠期间HCQ浓度及其与结局的关系。我们对2013-2016年单中心妊娠风湿病患者HCQ进行了一项观察性研究。采用高效液相色谱/质谱法分析血清样品。初次接触HCQ分为非治疗性（≤100 ng/mL）和治疗性（bb0 ~ 100 ng/mL）。分类结果采用Fisher精确检验，连续结果采用线性回归模型、Wilcoxon符号秩检验、Kruskal-Wallis检验、t检验和方差分析。我们分析了来自50例风湿病患者的145份样本，其中56%患有系统性红斑狼疮（SLE）。每个孕期个体间HCQ浓度差异很大。平均药物水平≤100 ng/mL的SLE患者的平均医师整体评估（PGA）评分明显高于平均药物水平≤100 ng/mL的患者（0.93 vs 0.32, p=0.01）。平均药物水平≤100 ng/mL的SLE患者中，83%的患者早产（n=6），而平均药物水平≤100 ng/mL的患者仅21% (n=19), （p=0.01）。在非sle患者中，HCQ水平与早产或疾病活动无关。由于高和低HCQ水平都与SLE的早产和疾病活动相关，因此有必要进一步研究HCQ在整个妊娠期的配置，并阐明药物水平与结局之间的关系。
Pregnancies in women with active rheumatic disease often result in poor neonatal outcomes. Hydroxychloroquine (HCQ) reduces disease activity and flares, however, pregnancy causes significant physiologic changes that may alter HCQ levels and lead to therapeutic failure. Therefore, our objective was to evaluate HCQ concentrations during pregnancy and relate levels to outcomes. We performed an observational study of pregnant patients with rheumatic disease on HCQ from a single center during 2013–2016. Serum samples were analyzed using HPLC/MS. Primary HCQ exposure was categorized as non-therapeutic (≤100 ng/mL) or therapeutic (>100 ng/mL). Categorical outcomes were analyzed using Fisher’s Exact Test and continuous outcomes using linear regression models, Wilcoxon signed rank test, Kruskal-Wallis test, t-test, and ANOVA. We analyzed 145 samples from 50 patients with rheumatic disease, 56% of whom had systemic lupus erythematosus (SLE). HCQ concentration varied widely between individuals at each trimester. Mean physician global assessment (PGA) scores in patients with SLE were significantly higher in those with average drug levels ≤100 ng/mL compared to >100 ng/mL (0.93 vs 0.32, p=0.01). 83% of patients with SLE and average drug levels ≤100 ng/mL delivered prematurely (n=6), compared to only 21% with average levels >100 ng/mL (n=19), (p=0.01). HCQ levels were not associated with prematurity or disease activity in non-SLE patients. With both high and low HCQ levels associated with preterm birth and disease activity in SLE, further study is necessary to understand HCQ disposition throughout pregnancy and clarify the relationship between drug levels and outcomes.
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影响因子：
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作者：
Clowse, Megan E. B.;Magder, Laurence;Petri, Michelle
通讯作者：
Petri, Michelle
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：
Clowse, MEB;Magder, LS;Petri, M
通讯作者：
Petri, M
影响因子：
4.7
作者：
Feldman CH;Yazdany J;Guan H;Solomon DH;Costenbader KH
通讯作者：
Costenbader KH