I am very excited and honored to congratulate the Spondylitis Association of America (SAA) on 30 years of service and support to the Spondyloarthritis Community. During the mid 1980s when I had just completed one of the early studies of DNA markers in AS, I was asked by SAA co-founder and former Executive Director, Jane Bruckel, to join the first SAA Medical Advisory Board, having served as its Chairman in 1994 and 1995. I also have worked with SAA in research efforts, studying what causes this disease, overseeing the SAA Family Genetic Project (beginning in 1998), which evolved into the NIH-funded North American Spondylitis Consortium (NASC)(1999-2004), which in turn evolved into my NIH-Funded Program Project Grant on the Genetic Basis of Ankylosing Spondylitis. This study was initially funded in 2006 and continues to this day.
More recently I am working with SAA in creating the SAA/SPARTAN AS Patient Registry. I have also worked with SAA in an administrative capacity, having served on the SAA Board of Directors since 2007. Of particular importance to the rheumatology community is the fact that SAA was a partner in the establishment of the Spondyloarthritis Research and Treatment Network (SPARTAN) – an organization of rheumatologists focused on the causes, epidemiology and management of spondyloarthritis of which I was a founding member in 2003, and for which the SAA remains as the fiscal agent to this day.
In considering what are the ten most important questions facing the Spondyloarthritis Community at present, I would suggest the following:
It takes up to 10 years between the time that the back pain begins and the x-rays turn positive for sacroiliitis, the hallmark of AS. This condition has been called ‘pre-radiographic’ axial spondyloarthritis. More recently, as groups of patients from Europe have been followed, it has become evident that many never go on to develop radiographic sacroiliitis, yet have other classical spondyloarthritis features (inflammatory back pain, positive MRIs for inflammation around the sacroiliac joints, HLA-B27 positivity, enthesitis, uveitis, positive family history, etc). This condition is called axial spondyloarthritis (AxSpA), and many consider AS to be part of this disease spectrum. Women with normal inflammatory blood markers who have AxSpA are more likely NOT to progress to AS. This has led to the development of criteria for axial spondyloarthritis as a disease entity, although the accuracy of these criteria as applied by doctors to patients in the general population is still being debated.
Data from a NHANES 2009-2010 study suggest that nearly one in five Americans have chronic low back pain. Up to a third of these people have inflammatory back pain (pain present every day that is worse in the morning, that normally starts before age 45, is improved by moving about or “limbering up”, is not helped by rest and which responds to nonsteroidal anti-inflammatory drugs). Axial spondyloarthritis was found by the NHANES study to occur in at least 1.4% of the general population, with up to 40% of these people having AS.
Unfortunately, there is a lack of emphasis on both back pain and spondyloarthritis in the U.S., both among clinicians and in medical schools. At the NIH, at a time when large amounts of research dollars were spent on rarer diseases such as lupus and rheumatoid arthritis, spondyloarthritis was relatively neglected. This is not the fault of the NIH; the fact is there are not many rheumatologists who are interested in spondyloarthritis that have applied for funding – which was one of the reasons SPARTAN was founded. In fact, many rheumatologists will not see patients with chronic low back pain. In one recent survey of patients with chronic low back pain in North Carolina, only 14% of patients had ever seen a rheumatologist. Among rheumatologists, many still use drugs such as methotrexate and sulfasalazine to treat the spinal pain associated with AS, even though numerous clinic trials have shown them not to be effective. Clearly, work needs to be done here in education and raising interest in the medical community.
Over 40 genes have now been implicated in causing AS. This has led some companies to develop panels of genes to determine if one is at risk for AS. The problem is that at present we only know about 25% of the overall risk for this disease and 80% of the known risk comes from HLA-B27 itself. The contributions of the other 39 or so other genes are individually very small in comparison. Further work is underway to determine additional genes and, more importantly, how these genes interact with each other to cause AS. Until this information is available, it is premature to recommend getting your “AS Gene Panel” checked to see if you have AS.
This should be done with consultation with your rheumatologist and a careful clinical evaluation. Instruments have been developed for this purpose (e.g. the Bath Ankylosing Spondylitis Disease Activity Index, or BASDAI and the Ankylosing Spondylitis Disease Activity Scale or ASDAS). The latter utilizes blood tests such as the sed rate or C-reactive protein levels (CRP). However these tests are imperfect and miss many people with otherwise active AS. What is clearly needed is a better blood biomarker for active AS and AxSpA.
Earlier data from clinical trials with anti-TNF agents in AS did not find an impact of these agents on the x-ray progression of this disease, despite the dramatic improvement given by these drugs on symptoms and day to day functioning. Looking at recent data from a collaboration of the Prospective Study of Outcomes in AS (PSOAS) and the Toronto University Health Network Spondylitis Program, anti-TNF drugs do indeed appear to slow the radiographic progression of this disease, especially if they are given in the first 10 years of the disease. It takes a few years before these differences are seen, which likely is why the earlier shorter term studies did not detect this.
Data from European AS cohorts, from PSOAS and from the Toronto University Health Network Spondylitis Program all show that only about half of patients with AS need an anti-TNF agent. At least half of AS patients are well controlled on nonsteroidal antiinflammatory drugs alone, or in some patients, the disease may become inactive and the pain cease on its own.
The cost of health care in the U.S. is more expensive than anywhere else in the world and has increased dramatically in recent years. Medication costs have been a major driver of these increases. Using an anti-TNF agent costs over $30,000 per year in each patient, and using these drugs to treat AxSpA, which is much more common than AS, is currently being considered by the FDA, which would cause costs to skyrocket. Whether this is sustainable in the evolving health care economy is an open question. Another question is whether TNFs may be restricted in the future to those patients who studies have shown are most likely to benefit from them (those with elevated inflammatory markers i.e. CRP or sed rate or positive MRIs) and denied to those with longstanding AS or with negative inflammatory markers or negative MRIs.
There are two reasons for this. First of all, a minority of AS patients have such active disease that even anti-TNF agents, in standard doses, cannot cool off the disease. Some benefit from higher doses, others should be considered for some of the new non anti-TNF biologic drugs that are currently being tested. However, the more important reason for lack of adequate response to an anti-TNF agent is that the back or joint pain might not be caused directly by inflammation from AS. Spinal fractures, herniated discs, and bone spurs pressing against spinal nerves can cause back pain that is not helped by anti-TNF drugs. If you are not having an adequate response to your anti-TNF agent, you and your doctor need to consider if one of these other causes may be contributing.
Data from an NHANES 2009 study showed significantly lower HLA-B27 prevalence estimates for older adults, as opposed to younger U.S. adults (3.6% for those 50-69 years of age vs. 7.3% for those 20-49 years, respectively). The reasons for this are not clear; one explanation is that it is a statistical fluke, although another explanation is that there is something about being HLA-B27 positive that is associated with a shorter life span. This observation clearly needs to be confirmed, and if found in another group, studies done in HLA-B27 positive people to determine why.
“The Spondylitis Association of America is honored and grateful to Dr. John Reveille for his decades-long dedication on behalf of those whom we serve and for his groundbreaking research in spondyloarthritis.”
—Laurie M. Savage, Executive Director
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