Rheumatoid arthritis clinical trial sifts blood for disease risk

The StopRA trial has screened more than 20,000 people, looking for antibody that greatly increases the risk of rheumatoid arthritis, an autoimmune disease that attacks the joints
August 4th, 2020
Becky Dittman with (from left) stepson Sam Kannady, husband Brian Kannady, and sons Tyler Dittman and Chase Dittman. Becky is enrolled in a rheumatoid arthritis clinical trial.
Becky Dittman with (from left) stepson Sam Kannady, husband Brian Kannady, and sons Tyler Dittman and Chase Dittman. Dittman is enrolled in a rheumatoid arthritis clinical trial to screen for a blood market that indicates increased risk for the disease. Photo courtesy of Becky Dittman.

Until relatively recently, neither Becky Dittman nor Elizabeth Wethington knew much about rheumatoid arthritis. They’d heard of it in passing, but no family members, friends or acquaintances that they knew of suffered from it.

Wethington’s only brush with rheumatoid arthritis (RA) came as a young girl. She recalls seeing the gnarled and swollen fingers of one of her grandmother’s friends who she learned had the disease.

“It was an early lesson, but it wasn’t connected to me,” says Wethington, now 44. “I didn’t know the day-to-day struggles she had.”

When Dittman, 49, first Googled rheumatoid arthritis about a year and a half ago, she was looking for black-and-white information about the disease but found only a sea of gray.

“I was looking for causes and cures and what can be done to stop it, but there was not a lot of conclusive info out there,” she said. “Everything was very vague and general. That was scarier than having the facts of what you can do about RA.”

On the trail of rheumatoid arthritis

Today, both Dittman and Wethington are taking an active role in research that aims to increase understanding of and possibly ease or even prevent the effects of rheumatoid arthritis, an autoimmune disease that attacks and inflames the lining of the joints. The disease causes symptoms that include pain, swelling, fatigue, loss of sleep, and a general flu-like feeling, said Dr. Kevin Deane, associate professor of Medicine-Rheumatology at the University of Colorado School of Medicine.

Elizabeth Wethington, who is part of a rheumatoid arthritis clinical trial, with son James and daughter Margarita. Photo courtesy of Elizabeth Wethington.
Elizabeth Wethington with son James and daughter Margarita. Washingon is enrolled in a rheumatoid arthritis clinical trial and receives a daily year-long course of hydroxychloroquine or a placebo. Photo courtesy of Elizabeth Wethington.

Deane is principal investigator for an ongoing trial with the shortened name StopRA that is recruiting patients to UCHealth hospitals and more than a dozen others around the country. The goal: screen for a blood marker – anti-cyclic citrullinated peptide, or anti-CCP3 – that indicates significantly increased risk for rheumatoid arthritis. The trial tests the effectiveness hydroxychloroquine versus a placebo in preventing the onset of RA in those individuals with the marker.

The disease affects about 1 % of people with normal levels of anti-CCP who also have no first degree relatives (mother or father, for example) with the disease — about 1.3 million people in the United States. But people with abnormal levels of the anti-CCP3 antibody have a 50 percent chance of getting RA within three years, Deane said.

“The risk with the marker is not 100 %, but we feel it’s strong enough to try to intervene to try to learn how we can prevent people from going on to get full-blown RA,” Deane said. “Because once that develops, it’s a forever disease that requires lifelong therapy.”

The risk for individuals with a first-degree relative with RA increases five to sevenfold across the general population, Deane said, making them a particularly attractive screening target for anti-CCP3. But he emphasized that the screening is open to anyone 18 years or older who wants it.

Rheumatoid arthritis clinical trial: drug vs. placebo

Those who enroll in the randomized trial will receive a daily year-long course of either hydroxychloroquine – a drug already used to treat patients with RA, as well as lupus and malaria – or a placebo. Deane said hydroxychloroquine – which he said went from being “a drug no one had heard of” to a sudden subject of controversy after President Trump touted it as a “game-changer” for the treatment of COVID-19 – helps to “reset the immune system” and control inflammation in patients with RA.

“Patients with RA take it once a day with typically very few side effects, and it’s very well tolerated,” Deane said. “That makes hydroxychloroquine a good drug for this type of prevention trial where the safety and tolerability of a drug are very important.”

Enrolled patients meet regularly with their study team, which follows them for two years after completing the medication regimen to assess how many in each group contract RA within the three-year period.

Dr. Kevin Deane, principal investigator for StopRA, a rheumatoid arthritis clinical trial.
Dr. Kevin Deane, principal investigator for the StopRA, a rheumatoid arthritis clinical trial. Photo courtesy of Kevin Deane.

The ideal study outcome will determine if hydroxychloroquine really does trigger a reboot of the immune system, thereby preventing the onset of RA, Deane said. As he put it, “That will be the golden apple of success.”

But whatever the rheumatoid arthritis clinical trial data reveal, simply identifying more patients at high risk for RA and following them is beneficial, Deane added. He noted that on average, patients with RA experience symptoms for two years before they receive a diagnosis and treatment. By that time, the disease may be so severe that they require expensive treatments that carry their own risks, such as suppressing the immune system and increasing the risk of infection.

“If we can identify the disease earlier, we can get patients on treatment earlier,” Deane said. “That’s important even if prevention doesn’t happen.”

Slow sift for subjects

The trial, which began four years ago, had recruited 121 patients as of early July, about 60% of the way towards the goal of 200. To find them, study sites have screened more than 20,000 people, Deane said. The challenge is twofold. First, the percentage of people with elevated levels of anti-CCP3 is small. Second, most blood tests don’t routinely screen for anti-CCP3.

“We are very excited about the enrollment number,” Deane said, “but these are hard people to find. We have to dig deep to find them.”

In Colorado, the digging extends to 9Health Fairs, which include the anti-CCP3 screening in blood tests. The rheumatoid arthritis clinical trial has also gotten support from the Arthritis Foundation and rheumatologists and primary care providers in private practices that Deane and other study leaders contact, encouraging them to refer individuals who are possible candidates for the study.

The outreach in Colorado has paid off, Deane said: 65 of the 121 study enrollees have come from Colorado, and many have been referred from UCHealth.

“We’ve had excellent partnerships across the state to enroll that many subjects,” he said.

RA clinical trial volunteers light the way

The partnerships, of course, include the patients who agree to commit their time to the study. Becky Dittman and Elizabeth Wethington came to the study via different paths, but they share an interest in assisting clinic researchers in their fight against RA.

Dittman, a human resources benefits specialist for a Broomfield-based company, has finished her one-year medication regimen and now sees Deane and his team every few months for monitoring. So far, she said, she has no symptoms of RA.

How should RA patients protect themselves during the COVID-19 pandemic?

Dr. Kevin Deane says that the limited data available indicates that people with full-blown RA and who are on immunosuppressant drugs have a slightly increased risk for more severe COVID compared to people without RA.

“In particular, if they are taking regular steroids they have a higher risk,” Deane said. “It is difficult to quantify but the risk for severe COVID related to RA is likely less than other risks such as age, diabetes and obesity.

“At this time, we are asking individuals with RA to take the usual precautions such as social distancing, handwashing, and face coverings,” Deane said. He added that patients should not taper or stop their medications without direct guidance from a rheumatologist.

“For those patients who do contract COVID-19, we do recommend that they stop some of their RA medications,” Deane concluded. However, he noted that the guidelines can change, so they should again talk to their rheumatologist. More guidance is available at https://www.rheumatology.org/Portals/0/Files/ACR-COVID-19-Clinical-Guidance-Summary-Patients-with-Rheumatic-Diseases.pdf.

She enrolled in the StopRA trial after seeing her primary care physician for joint pain that lingered in her left hand. Blood tests revealed the elevated anti-CCP3 marker, and her PCP let her know about the study, telling her she’d be a perfect candidate. Dittman then reached out to Deane’s study team to let them know she was interested in enrolling, which she did in January 2019.

Reading up on RA didn’t provide much comfort, Dittman said. She was looking for a precise path forward to address her risk but didn’t find one.

“There wasn’t a ton of concrete information,” she said. “There are so many unknowns about RA, and that’s scary. I was not hopeful. It’s depressing if you read about all the symptoms and possible things that can happen to you through the process of the disease.”

Necessary precautions

Instead of throwing her hands up in despair, Dittman took a positive step forward for herself and others. She said she’s always tended toward moderation, but now makes sure she exercises regularly, including taking walks twice a day. She and her husband, two sons and stepson also moved into a one-story ranch home in Arvada last fall so she could avoid climbing stairs in the event symptoms of RA emerge.

Joining the study helped to take some of the mystery out of RA, Dittman added. It gave her a “heads up” about her risk, made her more conscious of how she feels, and protected her with specialists familiar with a frightening disease.

“I feel like I have a team on my side,” Dittman said. She wants others to have the same benefits.

“I just felt I had to do something because I didn’t want someone else to feel the way I did,” she said. “Now that I have been part of this study, I have hope that they are going to figure this out, that the medications will get better and have fewer side effects. We’re getting there through research.”

Addressing autoimmune risk

Elizabeth Wethington, an administrative assistant in Aurora, received news of her abnormal anti-CCP3 levels last October after being hospitalized at UCHealth University of Colorado Hospital on the Anschutz Medical Campus. Her rheumatologist at UCH then connected her with the study.

Although she knows of no family history of RA, Wethington said she “has a penchant for developing autoimmune disorders,” including celiac disease and Graves’ disease. She believes those disorders increase her risk for developing another, like RA. With that in mind, she joined the study in January 2020. She continues to take her study medication and now sees Deane and his team every three months.

Thus far, Wethington said, she’s experienced no joint pain. Interviewed in mid-July, she said she’d just finished helping to paint the deck of the home she shares with her husband of 17 years and two children. In addition to plenty of typing required by her job, she knits and sews frequently and describes herself as “exceedingly active.”

Elizabeth Wethington (far left) skis with (from left) son James, husband Mark and daughter Margarita. Photo courtesy of Elizabeth Wethington.
Elizabeth Wethington (far left) skis with (from left) son James, husband Mark and daughter Margarita. Photo courtesy of Elizabeth Wethington.

She wants to keep it that way and sees the study as a safeguard for her health, even if she’s taking a placebo. She said, for example, that Deane’s team and her rheumatologist stay in close communication with one another and note any changes in her condition.

“Seeing my physicians more frequently is wonderful, whether I’m taking the medication or not,” Wethington said. “I’ll find out very quickly if I transition to RA. I’ll be right there and ready to get care.”

Contributing to science

Wethington calls the study “a great opportunity to learn about a disease that might affect me sometime in the future,” but avoids “potentially scary information” about RA that she might read on the web.

“I’m trying to live in the moment,” she said. “I take each day as it comes and report back [to my providers].”

Like Dittman, Wethington also enrolled in the study as a way to improve the future lives of patients with the disease.

“Science needs data in order to work,” Wethington said. “If I can help others by the use of my blood or tissue, I am happy to donate and help further science. If I can help the betterment of others, this is absolutely how I want to contribute.”

For his part, Deane believes the StopRA trial can raise awareness of RA and possibly build the testing infrastructure needed to find many more people at risk of the disease and those in early phases that require less aggressive treatment.

“Nobody thinks twice today about getting a blood test for cholesterol,” he said. “We would love to get RA to that point. This study could help to move public health in that direction.”

For more information about RA and the StopRA trial, visit https://stop-ra.org/.

 

About the author

Tyler Smith has been a health care writer, with a focus on hospitals, since 1996. He served as a writer and editor for the Marketing and Communications team at University of Colorado Hospital and UCHealth from 2007 to 2017. More recently, he has reported for and contributed stories to the University of Colorado School of Medicine, the Colorado School of Public Health and the Colorado Bioscience Association.