Clinical Epidemiology Program Advances Rheumatology Care

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In Massachusetts General Hospital's Clinical Epidemiology Program, rheumatologists are utilizing multidisciplinary collaborations, advanced mechanistic research tools and omics sciences to advance rheumatology care. As part of Mass General's Division of Rheumatology, Allergy and Immunology (RAI), their expansive scope of work involves outcomes research as well as clinical trials, biomarker studies and mechanistic studies on clinical topics including crystal arthropathy, inflammatory arthritis and complex multiorgan conditions caused by autoimmune inflammation.

"We have clinical cohorts of these conditions. We follow them, do outcomes research and try to improve and advance our patients' health—and eventually, human health. We want to translate this research into clinical trials so we can improve practice guidelines and advance clinical care," says Hyon Choi, MD, program director of the Clinical Epidemiology Program and clinical rheumatologist.

"We are also strong in our epidemiologic and causal inference methodology," he says. "We do a lot of methodologic research and publish papers to try to correct the misinformation and misapplication of methods."

Dr. Choi's team is heavily invested in training the next generation of rheumatology scientists through seminars, training programs, fellowships and mentored research. "Our program is growing every year, and our new graduates are getting awarded with National Institutes of Health (NIH) and foundational funding as they grow."

Multidisciplinary Collaborations Advance Rheumatology Research

The Clinical Epidemiology Program is located within the Mass General Department of Medicine's Mongan Institute. The institute brings together senior and junior faculty members, fellows, postdocs and trainees who use translational research, clinical epidemiology and implementation science to investigate specific areas of interest. Their physical proximity facilitates and encourages collaboration.

"The atmosphere at Mass General is second to none. With so many experts around you, what you need is never far—whether it's at Mass General, Mass General Brigham or in the city of Boston itself," says Dr. Choi. "Many people from around the world come to us to learn. That creates so much synergy and great collective work."

With support from NIH funding, foundations, industry and Mass General leadership, as well as department support, Dr. Choi's team works closely with disciplines within the structure of the institute including:

• Bioinformatics
• Gastroenterology
• Genetics
• Health service research
• Infectious disease
• Medical practice evaluation center
• Primary care
• Pulmonology

Exploring Gout Epidemiology and Comorbidities

Inflammatory arthritis, particularly crystal-induced conditions such as gout, pseudogout and rheumatoid arthritis, remains one of Dr. Choi's principal areas of interest. Gout incidence worldwide continues to rise, especially in the U.S. and other high-income societies with Western lifestyles. Increasing gout rates are also associated with more gout-related hospitalizations over the last two decades.

"Gout has become a public health issue, so we are focusing on how to reduce the incidence to levels seen several decades ago," says Dr. Choi. "We are looking to understand why this is happening, find the risk factors, prevent gout and intervene effectively."

Dr. Choi has been utilizing state-of-the-art mechanistic research tools, such as genome-wide association studies, to find more ways to develop new drugs, improve gout care and predict gout development in high-risk patients. His team is also exploring metabolomics and the microbiome to better understand where clinicians can intervene in the disease process to improve symptoms and prevent the condition. His research also involves preventing gout-associated comorbidities, such as heart attack, stroke, diabetes and chronic kidney disease.

"We are clarifying what is causing what, because we are very puzzled by the close coexistence of gout and these cardiometabolic conditions," says Dr. Choi. "More recently, we have discovered that insulin resistance itself is driving uric acid levels, the cause of gout. The next question is how can we intervene in the development of these conditions. We have to do what the diabetologists are doing and reduce insulin resistance and diabetes risk through weight loss and good diet. That would be the best way to approach these cardiometabolic conditions, in addition to trying to reduce uric acid to treat gout itself."

In their investigations, they have employed a technique called the Mendelian randomization method, which uses genes associated with traits as instruments to clarify causality.

"Using this method, it was clear insulin causally affects uric acid and not the other way around. Multiple methodological employments show the same unilateral direction," says Dr. Choi. "Another important related discovery came through trial analyses that involved giving people healthy diets like the Mediterranean diet or a low-fat, low-calorie diet. People lost weight with improved insulin resistance over six months to two years, and everything got better—uric acid levels and all cardiometabolic risk factors."

Investigating Rheumatology's Role in COVID-19 Outcomes

Mass General's rheumatology group is among the most active in COVID-19 research, publishing multiple studies during the pandemic. One explored rheumatology patients' susceptibility to COVID-19 and their outcomes in view of their immunosuppressed state. As part of their methodology, Dr. Choi's team reviewed the medical records of rheumatology and non-rheumatology patients.

"We found that rheumatology patients seemed to need more mechanical ventilation and ICU admission. We reported this initial finding and followed up by examining double the cases," says Dr. Choi. "We are doing an additional large data set analysis of the outcomes of COVID-19 patients versus non-COVID patients involving many centers across the entire U.S. to make a more generalizable epidemiologic assessment."

Dr. Choi notes that the inevitable knowledge gaps that occur in acute situations are a challenge of crisis epidemiology. "Investigators may not immediately realize the limitations of what they are doing. We are focusing on methodologically sound and reproducible research to navigate these crazy times we are living in."

Furthermore, by maximizing the use of available big data, including EMR-driven and omics data, Dr. Choi's team remains focused on unraveling rheumatology's unsolved mysteries and identifying how to resolve the crippling organ involvement of rheumatological conditions.

"We are working to provide precision medicine involving a lot of computation analysis to personalize treatments," he says.

Learn more about Clinical Epidemiology at Mass General

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