The Arthritis Foundation recently compiled a list of the Top Ten Advances in Arthritis and autoimmune disease research in 2006. Among the choices related to rheumatoid arthritis: the discovery of new genes associated with rheumatoid arthritis; a more effective test for RA that looks for antibodies against cyclic citrullinated peptide, or anti-CCP; positive research related to the safety and effectiveness of biologic response modifiers (TNF-inhibitor drugs); and the finding that children with Juvenile Idiopathic Arthritis (JIA) have as much as an 85% chance of relapse after periods of remission.
In my opinion, the most positive research of last year was the discovery of new genes related to RA and the new RA test. Since it is widely believed that the cause of RA is both genetic and environmental, these two discoveries will hopefully pave the way for earlier diagnosis and better targeted drugs in the future. I would like to hope that the recent genetic discoveries might even lead to a cure. In addition to the previously discovered gene, HLA-DRB1 (also known as the shared epitope), last year researchers found that at least one other gene that increases the likelihood of developing RA, and two others share possible connections. They found a statistically significant association between having rheumatoid factor-positive RA and carrying a particular form of the gene called PTPN22. They also believe that PTPN22 also influences age of onset of RA since those with the gene developed RA two years earlier than those without it. Specific variations in two other genes, CTLA4 and PADI4, also had a positive association (though a weaker statistical relationship) with the likelihood of developing RA.
As for the new test for RA, while the link between cyclic citrullinated peptide, or anti-CCP, and RA was already known, the new research found that testing for antibodies against cyclic citrullinated peptide, or anti-CCP, is much more specific than the traditional rheumatoid factor test for identifying people with RA. Scientists now also believe that anti-CCP antibodies may be a potential predictor of RA since the antibodies are present for years before disease symptoms are apparent. In addition, Swedish scientists found that smoking greatly increased the likelihood of the onset of RA in people with both the HLA-DRB1 (shared epitope) and anti-CCP antibodies. Smokers with both genetic markers are 21 times more likely to develop RA than nonsmokers who do not carry the genes.
The Arthritis Foundation ranked discoveries related to the safety and effectiveness of biologic response modifiers (TNF-inhibitor drugs) very high on the list. This included the FDA approvals of Rituxan as an RA treatment last February and Humira (adalimumab) for ankylosing spondylitis last August. Research also showed that combining adalmimumab or etanercept with DMARDS (specifically methotrexate) is more effective at treating RA than either drug alone. They also noted research finding that combining two TNF-inhibitor drugs together is unsafe. The Foundation also included studies showing effectiveness of abatacept in children with RA.
However, I think the Arthritis Foundation focused heavily on the positive research related to these drugs and failed to include other researched published last year that calls the safety of these drugs into question. For example, last May, a study published in JAMA (The Journal of the American Medical Association), reported that Humira and Remicade not only increase a patient’s likelihood of developing lymphoma, but that the two drugs have two times the risk of developing skin, gastrointestinal, breast and lung cancer as well as three times the risk of developing serious infections like pneumonia or TB. The study also found that the risk increases as the dosage of the drug increases, so patients on high doses (eg. 40 mg of Humira once every two weeks) have a greater risk of developing tumors than patients on low doses.
Perhaps the Arthritis Foundation was trying to keep the list truly to “advances” in the positive sense. But I would argue that negative research is also an advance because it leads researchers in new directions and pushes them to continually strive for more safe and effective alternatives. For example, Vioxx had another set back last year when research was finally reported last May that the incidents of cardiovascular problems related to the drug begin much earlier than had previously been reported and continue well after use of the drug has ended. Yes, that is negative safety research, but on the positive side, research published late in 2006 reports that Vioxx and the other COX-2 inhibitors may cause heart attacks and strokes because of a blood clotting effect linked to the inhibition of the COX-1 enzyme. Celebrex is the only COX-2 inhibitor currently left on the market. Hopefully these findings will take scientists in a new direction the development of safer NSAIDS.
What are your choices for last year’s greatest advances in the diagnosis, treatment or improvement of daily life for people with RA? Share your thoughts on the RA Message Boards or post a comment here.
Published On: January 23, 2007