Pioneering Registry Remains a Driving Force in Rheumatoid Arthritis Research

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The Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study (BRASS) examines the ability of laboratory analysis to predict the severity of rheumatoid arthritis (RA) and how individuals respond to different drug treatments. Launched two decades ago, the patient registry has played an important role in advancing the study of RA and development of related therapies.

Brigham rheumatologists Michael E. Weinblatt, MD, co-director of Clinical Rheumatology, and Nancy Ann Shadick, MD, MPH, are co-principal investigators of BRASS. Dr. Weinblatt says that he and his co-founders initially had two primary goals in mind for the registry.

“One, to develop a biorepository from patients with RA at our institution, which we had never had,” he says. “Two, to develop a very extensive clinical database on patients with RA, since that’s the primary rheumatic disease we see at the Brigham. The concept allows investigators around the world to access both the clinical data and the laboratory samples to further understanding of the disease.”

Nearly 1,600 Patients Enrolled

Each year, the Brigham sees about 4,500 patients with RA. This high volume has facilitated the growth of BRASS, which has enrolled nearly 1,600 patients since 2003. Some patients have been followed for close to 20 years, and Dr. Weinblatt estimates between 600 and 700 patients are being actively evaluated at this time.

Thanks in part to the vast biorepository, the BRASS research team has published more than 80 papers in journals such as Nature Genetics, JAMA, Arthritis & Rheumatology, Annals of Internal Medicine, The Journal of Rheumatology and Annals of Rheumatic Diseases.

Brigham rheumatologist Katherine P. Liao, MD, MPH, says that BRASS has been an extremely helpful resource for her throughout her career as an RA researcher. Her most recent study with BRASS, published in Arthritis Rheumatol, found that increases in inflammation are associated with lower cholesterol levels in RA—changes that, counterintuitively, are harmful for the heart.

“This study used a combination of data collected in BRASS over time, allowing us to look back and identify RA subjects who had changes in their levels of inflammation,” Dr. Liao says. “From there, we requested blood samples from BRASS and sent them to collaborating labs to obtain data on lipids and cardiac troponin.”

Exploring RA-related Lung Disease

Dr. Liao’s colleague at the Brigham, Jeffrey A. Sparks, MD, MMSc, has leveraged BRASS for investigations into RA-related lung disease, including dyspnea on exertion, incident RA-interstitial lung disease (ILD), bronchiectasis, pulmonary function test abnormalities and chest CT imaging abnormalities.

“BRASS has been an incredible resource for us,” Dr. Sparks says. “We used banked samples to identify fine specificity anti-citrullinated protein antibodies as biomarkers that predict future RA-ILD onset. We are also performing a sub-study in BRASS to investigate subclinical lung disease by performing high-resolution chest CT scans for research purposes.”

Outside of the Brigham, BRASS has provided fertile ground for investigators conducting primary research. According to Dr. Weinblatt, many investigators have used its data to support work funded by the Rheumatology Research Foundation and the National Institutes of Health. He adds that BRASS is funded by biotechnology and pharmaceutical companies, who have access to the data and have published academic research advancing the understanding of RA.

‘The Data and the Samples Will Always Be There’

Despite all that BRASS has made possible, Dr. Weinblatt admits one particular achievement has remained elusive: development of tests that identify patients who will or will not respond to certain drug therapies. But he hasn’t given up on that front.

“If somebody out there identifies a biomarker that they think is of interest, we can rapidly validate it because we have the samples, and we have the extensive clinical data,” he says. “Right now in rheumatology, our decision process about which drugs to use is truly empiric, not based upon data. The holy grail for us is to be able to do what the oncologists do: Tailor-make treatment algorithms that are based upon data.”

Dr. Weinblatt is confident that BRASS will continue to serve a valuable function in RA research for the foreseeable future.

“We will keep updating patient data as long as the registry is viable,” he concludes. “No matter what happens, the data and the samples will always be there.”

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