Stopping rheumatoid arthritis (RA) before it starts should be the goal of clinicians, said Kevin Deane, MD, PhD. To that end, Deane and colleagues have started StopRA.

That stands for “Strategy for the Prevention of Onset of Clinically-Apparent RA,” and Deane, a University of Colorado School of Medicine rheumatologist, and his colleagues have been working for a decade to make America’s first-ever RA prevention trial happen.

The National Institutes of Health-funded effort enrolled its first patients in April. As of early September, Deane and colleagues had enrolled 12 patients en route to their goal of 200 participants. Half will take daily hydroxychloroquine (HCQ) pills – a standard RA treatment – for a year; the other half will take placebo pills. Deane and co-investigators will then monitor them all for another two years to see if a disease whose progression has forever seemed inevitable might indeed be halted before its autoimmune cascade takes hold.

RA affects about 1 percent of the population, or more than 3 million people in the United States. The study Deane leads has 18 sites in addition to University of Colorado Hospital, including ones in Boston, Atlanta, Pittsburgh, Minneapolis, Oklahoma City, Omaha, San Francisco, Los Angeles and elsewhere. You’d think finding 200 people willing to try what could amount to an RA vaccine wouldn’t be so hard.

But most people with RA don’t know they have it until their immune systems have attacked their joints. At that point, patients can’t stop RA, they can only manage the symptoms. And so Deane and colleagues aim to populate their randomized, double-blind, placebo-controlled study with people who are still healthy but who have a 50-50 chance or higher of ending up with symptomatic RA within the next 36 months.

Numbers game

There’s a blood test that helps find such people. It looks for something called anti-cyclic citrullinated peptide-3, or anti-CCP3. People with RA have elevated anti-CCP3 levels. Deane has found that those without RA but with anti-CCP3 blood levels over a certain threshold have a  greater than 90 percent chance of getting RA, and a 50 percent or higher probability of it developing within three years.

But the chances of finding someone with high anti-CCP3 blood levels and no RA symptoms are vanishingly small. It took about 3,000 screenings to find those 12 participants, Deane said. He estimates that, to land 200 subjects, study researchers will need to do more than 18,000 screenings.

Fortunately, the StopRA team has help. The 9Health Fair is including anti-CCP3 tests in their screening panel, for one. The Arthritis Foundation is getting the word out to rheumatologists and arthritis experts across Colorado (Deane said other sites have similar efforts afoot). And it’s also made a difference that UCH is part of UCHealth, he said.

“The UCHealth system has helped us immensely,” Deane said. “We have a lot of rheumatologists in the system, especially here in Aurora, and up north.”

Family ties

The key is to find people whose immediate family members have RA, because those with close relatives with RA have a 5 percent to 7 percent risk of getting the disease in their lifetimes. Among the 12 participants in the study so far are family members of patients Deane sees in UCH’s Rheumatology Clinic, he said. In addition to screening family members of those with the disease, however, the StopRA trial is screening anyone who is willing to be tested.

While the science must play out over the next three years, there’s reason to hope that the StopRA study will bear fruit. Deane and his CU colleagues have been investigating the roots of RA for decades. The existence of biomarkers such as anti-CCP3 suggests that the disease starts long before RA’s damaging inflammation manifests. If that’s the case, early intervention could make a big difference.

A Dutch study whose results were presented in June sampled RA biomarkers and treated half its 81-patient, high-risk cohort with a single dose of the antibody rituximab. The investigators found that, while those who received the drug and those who got a placebo ended up with symptomatic RA at similar rates two years later, those in the placebo wing got the disease a year sooner, on average.

“The single dose delayed it, which is exciting,” Deane said. “It might speak to that we just need to treat it longer, or with a different agent to prevent RA completely.”

Long view

StopRA is designed to do just that. But regardless of the immediate outcomes, having years of data on 200 or so patients at high risk of RA will advance the science of the disease, Deane said. The study’s bounty of blood tests and evolving (or not-evolving) symptoms will provide Deane and team members, including colleagues Michael Holers, MD, and Christopher Striebich, MD, PhD, with new windows into the disease’s progression. The team will also gather diet and lifestyle-related data to capture factors such as smoking, recent pregnancy, and gum inflammation, which are associated with increased RA risk; as well as things like eating a lot of fish and drinking moderately, which may diminish RA risk.

“The study will give us a lot of understanding of the biologic processes that underpin the development of RA so future studies can target them more directly,” Deane said.

The goal is to turn RA into a preventable disease, he added, which would have an immense impact on lives wracked with pain and disability – not to mention the estimated $40 billion RA costs the United States each year.

“I think if we can identify and prevent it, we can make a huge positive impact on the health of society,” Deane said.

For more information on the StopRA trial, including a list of 9Health Fair events, visit www.stop-ra.org.