Our Communications Manager, Katie M. Kanagawa, interviewed Associate Professor of Epidemiology & Population Health (E&PH), Julia Simard, about her research on lupus and hydroxychloroquine in pregnancy. 

Can you start by telling us a bit about yourself? How did you get here (to Stanford Epidemiology)? Was there something in particular that attracted you to the fields of science, health and disease? 

My circuitous path to Stanford Epidemiology tells you a lot about me. Before I even knew epidemiology was a discipline, I was studying math and applied science at UC  San Diego, working on my teaching credentials (I wanted to teach high school math), and filling out an application to the French Culinary Institute in New York. After a series of conversations and soul searching, my path took a few more turns – graduate student in UCLA’s Statistics Department and statistician working at the Naval Base in Point Loma at the Naval Health Research Center. It was at NHRC that I learned about epidemiology and realized that it was what I had been searching for – a blend of math, statistics, sociology and behavior, medicine, public health, and more. It was one of those lightbulb moments where all of my interests and passions came together and I was shocked that I didn’t know about it until then.

Nine months later, I drove cross country with my (now) husband and got my MS and then ScD at the Harvard School of Public Health. In 2008, we were ready for our next adventure and moved to Sweden, where I started my postdoc at the Karolinska’s Clinical Epidemiology Unit and got to experience life in Sweden and population-based register data. The first couple of years at Karolinska were largely spent doing pharmacoepidemiologic research in rheumatoid arthritis and related conditions. After spending four years in Stockholm, we packed up 40 boxes and shipped them around the world so that I could join the faculty here at Stanford.

Let’s turn to your research. I understand you have spent some time researching lupus pregnancy. Can you start by telling us about this research and highlight a couple of key insights?

Sure, happy to. Lupus is a complicated chronic autoimmune disease that is more often diagnosed in women, with a number of reported disparities in occurrence and severity related to race, ethnicity, and other factors. Truthfully, my research in pregnancy outcomes in these populations was partly luck and some good advice from mentors. But as I started digging into what we knew or suspected about lupus pregnancy, I was surprised how little we knew and how much of it was likely outdated. For a long time, patients with any history of organ involvement in their lupus, even if quiescent, were advised against pregnancy. As a result, much of what made up the knowledge base reflected the experiences of patients with less severe lupus or those who had gotten pregnant possibly against medical advice. Now that pregnancy is no longer discouraged to the same degree, we need research to reflect the more contemporary clinical picture of a pregnant woman with lupus.

Since coming to Stanford, I have been working towards a better understanding of what the experience and risks are for this population. Using the Swedish Lupus Linkage I initially organized in 2011-2012, we observed unfavorable obstetric outcomes in pregnancies up to five years before a mother’s clinical diagnosis of lupus. These findings suggest that the underlying immunologic profile and alterations preceding a clinical diagnosis of lupus may contribute to these pregnancy outcomes. In follow-up work, we showed that women with lupus during pregnancy had a much higher risk of early-onset preeclampsia, and that preeclampsia explained a large proportion of the preterm deliveries in lupus pregnancies.

Let’s turn our focus to your recent R01 award, funding new research on hydroxychloroquine in pregnancy. Can you tell us about how this project got started, and what particular problem(s) it is seeking to address? 

This project was born out of a pilot that we did here at Stanford a few years ago that actually ended up as the MS thesis of one of our 2018 MS graduates. We found that women using hydroxychloroquine in lupus pregnancy had less preeclampsia and less preterm delivery, but because we were at a single academic medical center, we had relatively small numbers. This motivated the current R01 to replicate these findings in three large populations – Sweden, British Columbia, and a US-based cohort.

First, we want to determine whether using hydroxychloroquine during pregnancy in women with lupus prevents preeclampsia and how this may also influence anticipated reductions in the risk of preterm delivery. And second, because pregnant women with lupus appear to underutilize this medication despite its favorable safety and effectiveness profiles in lupus during pregnancy, we want to identify the barriers and facilitators of hydroxychloroquine use in pregnant women with lupus.

What is driving you to pursue this research at this point in time? What are you loving the most, or finding the most rewarding or challenging, about it? 

Preeclampsia is a life-threatening complication of pregnancy that accounts for 8% of US maternal deaths, and significantly contributes to fetal and neonatal mortality. However, we know little about what causes preeclampsia, and delivery of the placenta is the ultimate treatment. There are some hypotheses suggesting that hydroxychloroquine may be a useful treatment, but very little data exists to study this because there are only a few established indications for hydroxychloroquine. Given that up to 1/3 of pregnant women with lupus may develop preeclampsia, and that hydroxychloroquine is one of only a few treatment options to manage their lupus during pregnancy, this population seemed ideal to study this.

I am enjoying the multidisciplinary nature of this work, the opportunity to work with fantastic collaborators and colleagues from around the world, and our commitment to engage all stakeholders in this work, including patients. One challenge that I certainly didn’t anticipate when writing my grant in 2019 was that people around the world would be so familiar with hydroxychloroquine and have such strong opinions about it. It will be interesting to see how that might impact future use in pregnancy and what patients think about it.

What do you hope to accomplish with this new line of research? What larger impacts do you hope to make, scientifically and perhaps societally speaking, and who do you hope will benefit from this work? 

This work is fundamental to demonstrate effectiveness and provide an ethical argument for future clinical trials, as well as gain important insights into adherence and prescribing patterns for hydroxychloroquine. Given the established benefits of using this medication to manage lupus, especially in pregnancy when there are considerably few alternatives, understanding and helping overcome those barriers is important for the health of the mother and the success of the pregnancy. Further, I think that this research could inform future treatment options for women at risk of preeclampsia, whether or not they have lupus. There’s a lot to do before we can get there, but that potential impact is so motivating.

Is there any other work in the pipeline that you would like to tease here? 

Yes! There’s a methodologic spin-off from the hydroxychloroquine work that we’re setting up now to look at how the source of prescription data introduces bias and impacts the research questions that we can answer. Relatedly, I’ve been really interested in thinking not only about types of data but about the underlying real-world processes that generate the data that we study and how that perpetuate bias. We’re just kicking off a series of studies examining how cognitive bias in clinical decision making may contribute to health disparities in female-predominant diseases. This work builds off of a recent publication where we assessed whether physicians diagnoses of complex rheumatologic cases varied on the basis of the case’s sex, gender, and race.