羟氯喹在风湿性疾病合并妊娠中的水平：对母婴结局的影响。
Hydroxychloroquine Levels throughout Pregnancies Complicated by Rheumatic Disease: Implications for Maternal and Neonatal Outcomes.
机构信息
From the departments of Internal Medicine and Pediatrics, Duke University, and Duke Clinical Research Institute, Durham, North Carolina; Department of Pediatrics, Children's Hospital of Chicago, Chicago, Illinois, USA.
S.J. Balevic, MD, MHS, Assistant Professor, departments of Internal Medicine and Pediatrics, Duke University Medical Center and Duke Clinical Research Institute; M. Cohen-Wolkowiez, MD, PhD, Professor, Department of Pediatrics, Duke University Medical Center and Duke Clinical Research Institute; A.M. Eudy, PhD, Postdoctoral Fellow, Department of Internal Medicine, Duke University Medical Center; T.P. Green, MD, Professor and Chair, Department of Pediatrics, Children's Hospital of Chicago; L.E. Schanberg, MD, Professor, Department of Pediatrics, Duke University Medical Center; M.E. Clowse, MD, MPH, Associate Professor, Department of Internal Medicine, Duke University Medical Center.
出版信息
J Rheumatol. 2019 Jan;46(1):57-63. doi: 10.3899/jrheum.180158. Epub 2018 Oct 1.
OBJECTIVE
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.
METHODS
We performed an observational study of pregnant patients with rheumatic disease who were taking HCQ from a single center during 2013-2016. Serum samples were analyzed using high-performance liquid chromatography/mass spectrometry. Primary HCQ exposure was categorized as nontherapeutic (≤ 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.
RESULTS
We analyzed 145 samples from 50 patients with rheumatic disease, 56% of whom had systemic lupus erythematosus (SLE). HCQ concentration varied widely among individuals at each trimester. Mean physician's global assessment 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). Of patients with SLE, 83% with 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.
CONCLUSION
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 to clarify the relationship between drug levels and outcomes.
目的
患有活动性风湿病的女性妊娠常导致新生儿结局不良。羟氯喹（HCQ）可降低疾病活动度和发作；然而，妊娠会引起显著的生理变化，可能会改变 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，并将其与结局相关联。
方法
我们对 2013-2016 年间在一家中心接受 HCQ 治疗的患有风湿性疾病的孕妇进行了一项观察性研究。使用高效液相色谱/质谱法分析血清样本。主要 HCQ 暴露分为非治疗性（≤100ng/ml）或治疗性（>100ng/ml）。使用 Fisher 确切检验分析分类结局，使用线性回归模型、Wilcoxon 符号秩检验、Kruskal-Wallis 检验、t 检验和 ANOVA 分析连续结局。
结果
我们分析了 50 名患有风湿性疾病的患者的 145 个样本，其中 56%患有系统性红斑狼疮（SLE）。在每个孕期，个体之间的 HCQ 浓度差异很大。SLE 患者中，药物平均水平≤100ng/ml 的患者医生总体评估评分明显高于>100ng/ml 的患者（0.93 与 0.32，p=0.01）。在药物平均水平≤100ng/ml 的 SLE 患者中，83%早产（n=6），而药物平均水平>100ng/ml 的患者中，只有 21%早产（n=19；p=0.01）。非 SLE 患者的 HCQ 水平与早产或疾病活动度无关。
结论
由于高和低 HCQ 水平均与 SLE 患者的早产和疾病活动度相关，因此需要进一步研究以了解整个妊娠期间 HCQ 的分布情况，并阐明药物水平与结局之间的关系。
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