Can hydroxychloroquine prevent preeclampsia and preterm delivery in lupus pregnancy?

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This is a new application for an R01 award for epidemiologist Dr. Julia Simard, at Stanford University School of Medicine, who brings an innovative lens to the field as an early stage investigator building a research program focused on adverse pregnancy outcomes in patients with systemic lupus erythematosus. For her K01 award, Dr. Simard and colleagues showed that pregnant women with lupus are a highly-medicated group, who experience more adverse outcomes, including early-onset preeclampsia, preterm delivery, infection, and stroke. In recent pilot work, Dr. Simard found that hydroxychloroquine (HCQ), which is used to manage lupus during pregnancy, may prevent preeclampsia and preterm delivery. In two populations (one US and one in Sweden), Dr. Simard also found that fewer than half of pregnant women with lupus use HCQ, despite recommendations. This has been corroborated by others as well. Dr. Simard builds upon this work in the present application via three large international populations to determine whether HCQ reduces the risk of these adverse outcomes in lupus pregnancies. Dr. Simard will partner with colleagues in Sweden, Israel, and Kaiser Permanente of Northern California’s Division of Research in the United States. These data include details on ordered and filled prescriptions, and often unavailable data on antiphospholipid antibody status and parity, two critical factors in lupus reproductive research. In aim 1, Dr. Simard will determine whether preeclampsia risk is reduced in women who use HCQ during pregnancy. In aim 2, Dr. Simard will examine preterm delivery, partitioning spontaneous from medically-indicated, to examine overall risks and medication by preeclampsia and other factors such as glucocorticoid use and gestational diabetes. In aim 3, Dr. Simard’s team will identify barriers and facilitators of HCQ use in pregnant women with lupus using an innovative mixed methods design. After evaluating patient adherence and guideline adherence by clinicians in the large US and Israeli databases, they will identify subsets less likely to adhere and examine how they differ from adherent patients. Then partnering with patients and providers, they will use these quantitative findings to identify barriers and facilitators of adherence from the patient and provider perspectives using focus groups. This aim will provide key information on HCQ use and prescription practices to improve the analytic paradigm and inform our clinical understanding HCQ use in lupus pregnancy, and provide foundational support for clinical care and possibly, a future clinical trial.