Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 57-63 |
| Number of pages | 7 |
| Journal | Journal of Rheumatology |
| Volume | 46 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2019 |
Funding
This study was provided by the US National Institute of Child Health and Human Development/National Institute of General Medical Sciences (NIGMS/NICHD 2T32GM086330-06), the Derfner Foundation, and Duke Health Private Diagnostic Clinic ENABLE. 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. Funding for this study was provided by the US National Institute of Child Health and Human Development/National Institute of General Medical Sciences (NIGMS/NICHD 2T32GM086330-06), the Derfner Foundation, and Duke Health Private Diagnostic Clinic ENABLE. 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. Address correspondence to Dr. S.J. Balevic, Duke University Medical Center, 2301 Erwin Road, Durham, North Carolina 27710, USA. E-mail: [email protected] Accepted for publication July 3, 2018.
Keywords
- Hydroxychloroquine
- Pregnancy
- Systemic lupus erythematosus
ASJC Scopus subject areas
- Rheumatology
- Immunology and Allergy
- Immunology