A conversation with the founding and current directors of the UCSF Arthritis Clinical Trials Center on its 10th anniversary

Ten years ago, with major support from the Rosalind Russell Medical Research Center for Arthritis, the UCSF Arthritis Clinical Trials Center opened its doors with the goal to accelerate the development of more effective treatments with less harmful side effects. With large numbers of potentially better drugs being developed in laboratories across the country, including labs at UCSF, the founding of the Arthritis Clinical Trials Center responded to the national need for outstanding university-based programs to test new treatments with patient volunteers. Over the years—with continued support from the Rosalind Russell Center—the UCSF Arthritis Clinical Trials Center has become perhaps the largest and most respected resource of its kind.

Dr. David Wofsy was the driving force in establishing the UCSF Arthritis Clinical Trials Center and, for eight years, served as Director. Dr. John Davis, who came to UCSF in 1998 as Assistant Director of the Clinical Trials Center, assumed leadership two years ago.

Q: "Looking back 10 years, how has the arsenal of arthritis drugs changed?"
Dr. John Davis: "I think there has been a revolution in treatment for autoimmune rheumatic diseases in general. We've gone from having a small selection of very nonspecific drugs to a large number of very specifically targeted therapies for many different diseases. In arthritis, progress has been made in rheumatoid arthritis, in juvenile rheumatoid arthritis, in psoriatic arthritis and ankylosing spondylitis (an arthritis of the spine)."
Dr. David Wofsy: "We established the Clinical Trials Center because we anticipated, based on the flow of science, moving into an entirely different era. We weren't just going to have the next generation of drugs. We were going to have the first generation of drugs that was based on a clearer understanding of the mechanism of disease and how we can deal with that mechanism. And that's exactly what has happened. You could go back a quarter of a century prior to 1997 without finding any new drug approvals for any of the diseases John mentioned."
Dr. Davis: "This is an unprecedented time for patients with autoimmune disease. The new therapies are not only arresting development of such diseases as rheumatoid arthritis and psoriatic arthritis. There is evidence that they may be able to actually repair previous damage. Of course with all new advances come potential risks or side effects. Luckily, these have not been very common, but have included an increased risk of infection, especially reactivation of tuberculosis."

Q: "What role has the UCSF Arthritis Clinical Trials Center has played in this progress?"
Dr. Davis: "We have played a leading role in both national and international studies, looking at a number of different drugs for many different diseases. We've provided expertise in the design of clinical trials, going from pre-clinical development through the multi-center, multi-national studies that are being performed. We work closely with the National Institutes of Health, the Food and Drug Administration and with pharmaceutical and biotechnology companies in helping them design specific trials to study the drug under question and make sure it's a safe trial."
Dr. Wofsy: "Progress in clinical trial work is almost always a collaborative effort among multiple sites. You can't move the field forward from any one site, and we have been a part of literally every one of the drug development programs that have led to improved therapies in the last 10 years. Every single one of the newly approved drugs has at one point or another come through our unit and been studied here."

Q: "How many might that be?"
Dr. Wofsy: "I can think of six: three different inhibitors of tumor necrosis factor—etanercept [marketed as Enbrel], infliximab [Remicade] and adalimumab [Humira]; CTLA 4Ig which is marketed as abatacept [Orencia]; rituximab [Rituxan]; and anakinra [Kineret]. That said, there are certainly some of these programs in which we've played a much more dominant role. John doesn't single out his own role, but it needs to be singled out. The first demonstration that TNF inhibitors were effective in ankylosis spondylitis was done by John and actually done at a single site—our site—which is a very extraordinary thing to occur."

Q: "What would you say are the Clinical Trial Center's special strengths?"
Dr. Davis: "I think they are the breadth of what we provide to patients and to the scientists and physicians involved in arthritis. We're very strong in translational research, which refers to accelerating the speed at which new laboratory research findings have clinical application."
Dr Wofsy: "The skills and experience developed by the staff at the Clinical Trials Center have really made it possible for us to take a leadership role in the design of what's happening way beyond UCSF. So at this point, one wouldn't think of sitting down to design a trial in ankylosing spondylitis, for example, without seeking John's input. There are many examples of this. Also, we've really pushed ourselves to address some of the diseases that tend to be overlooked. We have been the major force in trying to make things happen in lupus and in vasculitis [an inflammation of the blood vessels that can block blood flow and seriously damage tissues and organs]."

Q: "When you look back at your involvement in the Clinical Trials Center, of what are you most proud?"
Dr. Davis: "I'm proud of the fact that we can give our patients access to state-of-the-art therapy. I'm also proud to give them hope. We take on a lot rare diseases where there was no hope before."
Dr. Wofsy: "I'm proud that in the decade that we've been doing this, numerous new drugs that we've contributed to have been approved and have improved the lives of probably hundreds of thousands of people with various forms of arthritis."

Q: "What's ahead for the Arthritis Clinical Trials Center?"
Dr. Davis: "We're moving into a new era where drugs are going to be more patient-friendly, meaning they will be in an oral form or another form that doesn't require multiple dosing. Also, we'll have a whole host of drugs available for a particular disease where there was only one or none in the past. And we're moving into an area of introducing genetic biomarkers that will identify patients who may respond particularly well to a particular drug."
Dr. Wofsy: "I think we're now passing beyond the first phase of the work where the most common diseases are the focus of attention and where rapid progress is made in those areas. We'll be focusing more on the less common diseases, which are going to take a little longer and be a little harder. Diseases like systemic lupus, systemic vasculitis and scleroderma-these are examples of diseases that we would hope would be the focus of attention in the next decade."

Q: "Is it an overstatement to think that there might some day be a cure for some forms of arthritis?"
Dr. Wofsy: "No, it's not an understatement. It's difficult to predict the pace of progress in biology. But the real goal in all of these diseases is to find the root cause. And when you know the root cause, then you begin to have an avenue for a systematic approach to a cure. Basic scientists at UCSF and around the country are trying to find out what really causes arthritis, and they will. Surely these diseases will be cured some day. They'll be prevented some day, like other diseases. There's no reason to think it will be different."

(Published June 2007 in Arthritis Progress Report, the newsletter of the Rosalind Russell Medical Research Center for Arthritis. To be added to our mailing list, please send us a note with your name and address to rrac@medicine.ucsf.edu. Your information will not be shared with any other organizations.)

"These diseases will be cured some day. They'll be prevented someday. There's no reason to think it will be different."

--Dr. Wofsy

"This is an unprecedented time for patients with autoimmune disease."

--Dr. Davis