Planting the Seeds of Discovery — Rheumatoid Arthritis Observational Cohort Study

reprinted from Issue 6, Spring 2008 of Frontiers of Medicine (PDF)

John Imboden, MD, chief of the division of rheumatology
at San Francisco General Hospital, with a patient
photo credit: Noah Berger


Planting the Seeds of Discovery — Rheumatoid Arthritis Observational Cohort Study

Imagine you had a state-of-the-art kitchen, a passion for cooking, and a number of friends you would love to have over. The only holdup to wonderful dinner parties is an unfortunate lack of stores nearby, requiring you to grow all of your own ingredients.

Such is the challenge for many doctors at UCSF, who have a record of superlative research and intriguing questions about their patients' diseases. However, to secure grant funding, they usually have to provide preliminary data showing their hypotheses have merit.

"It's a lot easier to make corn chowder if somebody provides you with the corn," says John Imboden, MD, with a smile. "Rather than giving you a couple seeds and saying, 'Find a field!'"

Imboden, who is chief of the division of rheumatology at San Francisco General Hospital (SFGH), wanted to make it easier to gather this data. So with Assistant Professor of Medicine Jonathan Graf, MD, he launched the Rheumatoid Arthritis (RA) Observational Cohort Study in November 2006.

With startup funds from the Department of Medicine, they have enrolled 350 patients with RA at SFGH and UCSF Medical Center, two of the department's main patient care sites. They will soon begin enrolling patients at the Veterans Affairs Medical Center (VAMC). They are well on their way toward their goal of enrolling 500 patients by the end of 2008.

Enrolled patients give permission for their clinical data to be included in an anonymous database, which allows their records to be searched and compared with other patients without revealing their identity.

The study has already helped launch several successfully funded grants, with a number of other grants pending. For example, Jennifer Barton, MD, is a rheumatology fellow who recently received a three-year Physician-Scientist Development Award from the American College of Rheumatology to study major differences in perception between physicians and patients about how the patient is doing.

Unlike diseases like diabetes, where patients can monitor their glucose levels, there is no gold standard for measuring the disease activity of RA. So good patient-physician communication about more subjective measures of the disease is particularly important.

In Barton's case, the preliminary data from the cohort pointed to some striking trends. Almost half the patients thought they were doing significantly worse than their doctors did. These patients were disproportionately women, African Americans and Latinos. Barton wants to investigate why there is so much discordance between these patients' self-assessments and their doctors', and whether this is related to poorer health in the long run.

"I really wouldn't have been able to do this project at all without the observational cohort," says Barton. "I would have had to do the groundwork of recruiting patients and collecting data myself, and as a second-year fellow, that would have been impossible. I was able to provide preliminary data from the cohort in the grant, and that helped enormously in getting funding."

Breaking New Ground

There are other observational cohort studies for RA, but UCSF's is unique in the level of diversity of the patients enrolled. The RA cohort includes one of the largest collections of Asian American patients in the world. Many of the patients are based at SFGH, and 70% of those enrolled in the cohort speak Spanish or Cantonese. In addition, the information is collected by the providers during the clinic visit – when there is time for observation and dialogue – rather than relying on mailed questionnaires.

In addition, the study has begun to collect tissue samples from patients. "Rheumatoid arthritis is a lifelong, chronic disease that doesn't change so much day to day," says Imboden. For example, it takes about five years for RA patients to develop deformities. Taking these tissue samples now will allow scientists to go back in time later on to analyze whether there are biomarkers associated with an increased risk for developing such deformities. This may also help develop more targeted prevention plans for specific patients, based on their risk factors.

"It's great that Dr. Imboden, a world-class laboratory-based molecular immunologist, is making this transition to more translational studies," says Arthur Weiss, MD, PhD, chief of the division of rheumatology at the UCSF Medical Center campus. "He's coming at it with a perspective that many people wouldn't have – not only collecting these samples, but knowing how to use them."

As well as encouraging research in rheumatology, the cohort study also has attracted interest from other fields. Funded and pending research grants focus on topics such as the interaction between depression and socioeconomic status in RA patients, and the relationship between RA and cardiovascular disease.

"There are investigators here who are quite interested in those kinds of questions, but hadn't been interested in rheumatoid arthritis," says Imboden. "Once we had the cohort, it became very apparent that we had some very interesting questions, and ways to answer those questions."

What is Arthritis?

Arthritis literally means joint inflammation, but it is often used to identify a group of more than 100 rheumatic diseases that may cause pain, stiffness and swelling in the joints and in areas close to the joints. Some common types of arthritis are:

osteoarthritis – which occurs when the cartilage that cushions the ends of the bones wears away.
rheumatoid arthritis – an inflammatory disease that causes pain, swelling, stiffness, and loss of function in the joints.
lupus – a chronic inflammatory disease that can affect various parts of the body, especially the skin, joints, blood and kidneys.
fibromyalgia – characterized by widespread pain in the muscles, ligaments and tendons, as well as fatigue and multiple tender points.
gout – occurs when needle-like crystals of uric acid build up in connective tissue, in the joint space between two bones, or in both.

According to the Centers for Disease Control and Prevention, arthritis is the most common cause of disability in the United States. About one in five adults report doctor-diagnosed arthritis.

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