About 1.5 million adults in the United States suffer from rheumatoid arthritis (RA), an autoimmune disease that causes the body to launch an attack against itself that yields painful inflammation and swelling of the joints. There are medications to treat the symptoms of RA, but what if the suffering could be prevented?
That’s the goal of the Autoimmune Disease Prevention Center (ADPC) at the University of Colorado School of Medicine. The initial idea is to identify people at risk for developing RA as a springboard for research into the roots of the disease and clinical trials of treatments to thwart it from progressing. Work on preventing some of the dozens of other autoimmune diseases that in aggregate afflict up to 8% of people should come later.
The ADPC launched a year ago under the direction of Dr. Kevin Deane, professor of Medicine – Rheumatology and William P. Arend Endowed Chair in Rheumatology Research at the School of Medicine. Deane led a large, long-running trial, StopRA, which was the first RA-prevention trial in the country.
StopRA screened thousands of people for a blood marker that indicates an increased risk for developing RA. The study investigated whether the drug hydroxychloroquine could forestall the development of arthritis and symptoms of RA.
Rheumatoid arthritis prevention trials launched
The drug proved ineffective for that purpose and the trial was discontinued, but it was part of a landscape that includes five other RA-prevention trials that tested different medications. Now Deane leads a larger study, dubbed StopRA: National, which will recruit at-risk individuals – many online – from rheumatology practices across the nation, including UCHealth’s seven clinics in Colorado, Deane said. He said the research team plans to begin recruiting participants in April.
“We’re building on the network that we started with StopRA,” Deane said. “We’re still recruiting people who are at risk for developing RA while also learning more about how RA develops and setting the stage for future studies.” Those might include trials of new preventive drugs, he said.
Deane said he anticipates that the ADPC will also extend work by his Division of Rheumatology colleagues that focuses on other factors that may trigger RA. For example, Drs. Kristin Demoruelle and Kristi Kuhn have conducted research into the roles of the lungs, mucosa – moist surfaces in body organs – and the microbiome as staging grounds for RA.
Dr. Meagan Chriswell, a former student in the School of Medicine’s Medical Scientist Training Program, was a key contributor with Kuhn to advancing understanding of the gut mucosal and microbiome links to RA. Further, the ADPC builds on longstanding work by Dr. Jill Norris, professor and chair of the Department of Epidemiology at the Colorado School of Public Health, into the epidemiology of autoimmune diseases.
“There are centers that have the term ‘prevention’ in them, but this institution is groundbreaking in its pre-RA research,” said Dr. Michael Holers, Smyth Professor of Rheumatology with the School of Medicine and director of Faculty Ventures at CU Innovations.
A complex effort to build the Autoimmune Disease Prevention Center
Despite this track record of success, Deane emphasized that the ADPC faces many challenges in negotiating the clinical and research labyrinth of autoimmune disease. There are more than 100, according to the Autoimmune Disease Association, and the factors that contribute to them are complex and often overlapping: genetics, environmental factors and inflammatory responses can be triggers that cause disruptions to the immune system.
“I think the phrase ‘it takes a village’ is really appropriate here,” Deane said. “Understanding how autoimmune diseases work and ultimately how you prevent them requires a lot of expertise.”
The village includes basic science researchers, staff to recruit at-risk individuals, experts to design clinical trials, and clinical researchers to follow patients over time. The effort also relies on analytics groups and statisticians to manage mountains of data and sift through it for clues that reveal the biology of different diseases, Deane said.
“We also require partnerships with companies that can help institute what you actually need to implement prevention,” he said. That includes pharmaceutical companies interested in developing drugs that target autoimmune diseases and diagnostic companies to build blood tests capable of identifying large groups of people at risk for these diseases, he added.
“What the center hopes to do is serve as a focal point for all these ‘villagers’ and focus their efforts so each can contribute their strength to the overall advancement of prevention,” Deane said.
Efforts to integrate research and treatment of autoimmune diseases
Holers said the ADPC is also a symbol of the relatively recent recognition that autoimmune diseases cannot be “siloed” by specialty. That’s because these conditions all trace back to the presence of autoantibodies that develop as various triggers that cause disruptions to the immune system, even before the cascades of symptoms develop in different parts of the body.
“The immune system affects all the organs,” he said. Ironically, though, the organ-based specialties of modern medicine have made it difficult to develop an integrated approach to preventing and treating autoimmune disease, Holer said. That is changing, he added, with the launch of the Office of Autoimmune Disease Research by the National Institutes of Health.
“It’s a big effort underway that I hope will continue to be funded to integrate autoimmune diseases across these siloes of organs into one big discipline,” Holers said. “I think that’s an important part of this solution.”
Holers added that the ADPC will focus on RA in the near term, but it is set up to collaborate with other specialties that treat autoimmune diseases.
“The way we have envisioned it is that rheumatoid arthritis is the test bed,” he said. “As the field evolves, and the prevention center pushes the science to identify individuals at risk for other autoimmune diseases, it will incorporate more and more of those.”
That expanding research points to a lofty goal, Holers added. “I think where we will wind up, hopefully, is a way by which we could screen for risk for almost all autoimmune diseases with a relatively simple blood test that is used in primary care.”
A continuation of significant progress in understanding autoimmune diseases
Deane underscored the work required to assemble the pieces of the autoimmune disease puzzle into a more coherent picture. He noted that when he began his rheumatology training nearly 25 years ago, the health care community had no biomarker to predict RA. Fifteen years ago, when he proposed the StopRA trial, it was rejected by two funding agencies.
“The thought was we would never want to give somebody who wasn’t sick yet an intervention to try and prevent future disease,” Deane said. “But yet in the past 10 years, we have had five trials completed to try and prevent RA.” He added that work has also been done on additional trials aimed at preventing Type 1 diabetes, lupus, psoriatic arthritis and other autoimmune diseases.
“We’re at a point where society is willing to accept calculating someone’s risk and then intervening to try and prevent disease,” Deane said. “That’s huge.”
Another important step forward for the field will be helping people at risk for autoimmune disease get involved in managing their health, Deane said. He and Holers both pointed to a half-century of work by cardiovascular disease providers to educate those at risk for heart attack and stroke to check their cholesterol, manage their diet, and take preventive medications to protect themselves.
“I think that’s critically important and should not be discounted,” Deane said. “When you are trying to prevent something, but people haven’t felt sick yet, you need people to be aware of the risk and to participate in the process. I think that concept is critically important.”
For more information about participating in the StopRA: National trial, visit the website.