Closer than Ever to Achieving a Cure
Dr. John Hardin’s career with the Arthritis Foundation has deep roots. He received Foundation fellowships in the 1970s and 1980s to advance his understanding of the causes and possible treatments of the disease. Today, he is giving back to our cause by directing the Foundation’s efforts to make even more progress in our persistent quest to prevent, control and ultimately cure arthritis.
How has arthritis research changed over the course of your career?
When I first started out, doctors were treating arthritis patients with gold injections and lots of aspirin. The results were about what would have happened with no treatment at all: On average, of every three patients, one would spontaneously get better, one would continue to have the disease, and the third would have aggressive disease that would eventually leave them crippled.
In the 1980s, we had a breakthrough with a drug called methotrexate, which was being used in cancer treatment. Today, it helps a large portion of patients get 50 to 75 percent better. But methotrexate doesn’t work for everyone, and it can weaken resistance to infection overall.
In 2000, we had another breakthrough with biologics: medications produced by living cells in an incubator. They bind to a specific molecule present in inflammation and inhibit it. In rheumatoid arthritis (RA), we know the immune system is activated in and around the joints, and that substances called cytokines are important in this process. The first set of biologics targeted a cytokine called TNF-alpha, which is very important in tissue injury. Newer biologics are now being developed as well. Biologics are absolutely life changing for many people. But most still have some flares of the disease, and they need continued use of these drugs to control that. It isn’t a cure, and a percentage of patients don’t experience an acceptable level of remission.
Where do you envision the next research breakthroughs occurring?
There is significant potential for breakthroughs in so many areas, especially in RA. I believe that the earlier people with RA are treated, the more effective the treatment will be. We need to identify biomarkers that can determine what kind of drug is most likely to be successful on a given patient. In other words, more personalized medicine. To achieve that, we need to create patient registries so we can analyze and correlate biological and treatment information for large numbers of people with this disease.
The Arthritis Foundation is helping fund data coordination for TETRAD (Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database), which was launched by the National Institutes of Health (NIH) in 2009. Our goal is to correlate genetic data of a large number of people with RA over the next two years. We are also working on an alternative approach to developing a very large registry for patients with RA. We refer to this new initiative as AIR (Arthritis Internet Registry), which was initiated by the Arthritis Foundation in 2010 and capitalizes on our relationship with the million-plus people who have RA. Housed on our website, an online questionnaire quickly confirms eligibility. Then a lab contacts participants to acquire blood samples and processes the data. This approach builds a real partnership of scientists and patients in seeking better ways to halt RA.
What about breakthroughs in osteoarthritis and juvenile arthritis?
The Centers for Disease Control and Prevention (CDC) estimates that 27 million Americans have osteoarthritis (OA) today, and that number is growing as our population ages. We also have an obesity epidemic, resulting in OA at early ages. There are also more athletic injuries – especially anterior cruciate ligament (ACL) injuries in girls and women, and a majority go on to experience life-altering arthritis in that joint. Presently we do not have an effective intervention for OA other than joint replacement surgery.
What is needed to move this field forward is a way to detect OA at a very early stage, even before any symptoms appear. In other words, we need a test that is the equivalent of a blood cholesterol measurement as a predictor of cardiovascular disease or an imaging strategy comparable to a bone scan for detecting osteoporosis. For this reason, we are working to identify biomarkers for OA. Our strategy is to further study a group of candidate measures to determine if any of them correlate with and predict clinical outcomes in patients with OA who have been followed over a significant period of time. The NIH has already collected the required material on a number of OA patients, and the Arthritis Foundation is promoting an analysis of this material to determine if any of the potential OA biomarkers has clinical utility.
Once we have a biomarker for OA, moving forward will be much easier. Pharmaceutical companies already have products on their shelves that could change the outcome for OA. These products have not yet been tested, because without a biomarker, relevant clinical trials could take many years to complete.
In addition to promoting development of a biomarker for OA, we are working with the Food and Drug Administration (FDA) to find ways to address new clinical trial designs that will dramatically speed up the drug discovery process.
Besides supporting researchers investigating arthritis in children, we’re working closely with the Childhood Arthritis & Rheumatology Research Alliance (CARRA), a national network of pediatric rheumatology centers, which the Arthritis Foundation helped found. Our investment in the accelerated juvenile arthritis research that CARRA makes possible will enable us to identify the best ways of matching patients with the right treatments at the right time.
What will be necessary to take us to the next level?
There is no question that the level and pace of arthritis research and funding must accelerate. We are talking about a disease that is a principle driver of health care costs in this country. There is no way to predict exactly how and when any breakthrough will take place, but we are working on some concrete initiatives, such as TETRAD and AIR, and we know how much investment they will require. None of the breakthroughs that we are looking for are going to happen without significant funding. And, of course, we need more than funding alone.
It is also critically important to encourage patients to participate in clinical trials. Pharmaceutical companies fund some patient research, but not enough. NIH grants usually only cover research that is already established. That is why the Arthritis Foundation funds Innovative Research Grants, which enable researchers to pursue and prove new approaches and ideas, which we need to do at a greater depth.
New breakthroughs also depend on improvements in patient education and advocacy to get arthritis drugs into the marketplace and ensure their safety. The Arthritis Foundation is the organization that represents the interests of patients with arthritis. We must bring the disease into the public consciousness like never before.
There is a huge deficiency in pediatric rheumatology, and we need more people to pursue it as a career. Our advocacy plan is focused on legislation to improve funding for arthritis, which will bring more people into the field and encourage the development of arthritis specialists.
The power of basic science today, compared to when I first began, is amazing. Who could have imagined how far we would come? When I started working in this field, we could hardly imagine how to isolate proteins in the body. Now we can produce them in a test tube. The scientific capability for a cure to arthritis is in our hands. Think about HIV that causes AIDS. It was an overwhelming disease that killed almost everyone who got the virus. But there was a great push for advances in treatment, and now it is so much more controlled. We need the same push in arthritis.
Why is supporting the Arthritis Foundation so important?
The Arthritis Foundation is involved not only in innovative research, advocacy and education, but also in pulling these elements together to take scientific discoveries through the process of research, funding and development, and to make them commercially available. The scientific community in the United States is very strong, with outstanding medical schools and research institutions that prepare people to embark on careers that can really make a difference. Unfortunately, 90 percent of potentially important research ideas go unfunded because they are based on unproven strategies.