Atul A. Deodhar, MD: The American College of Rheumatology, along with the Spondylitis Association of America and SPARTAN, which is Spondyloarthritis Research and Treatment Network, came up with the treatment guidelines. So the SPARTAN is this organization of rheumatologists within North America who are interested in spondyloarthritis studies. We published our guidelines first in 2016, and the new guidelines were just presented recently at the American College of Rheumatology annual meeting in Chicago in October of 2018. And these are the re-edited or refurbished guidelines that we had originally published in 2016.
These guidelines talk about which are the patients who are appropriate for the treatment, which are the patients who are appropriate for aggressive treatment, how you decide about which agents should be used in day-to-day practice, and the order in which you will add newer agents. So the treatment guidelines say that the first goal of therapy is to improve the signs and symptoms and treat the patient’s pain and fatigue as well as morning stiffness. As I said earlier, prevention of radiographic progression is still aspirational, and that is not part of these guidelines. We suggest that the first treatment should be physical therapy and nonsteroidal anti-inflammatory drugs. If the patient has significant symptoms and the disease is active—according to the guidelines, if the patient has significant signs and symptoms that are unbearable and that are caused by the disease itself—then we go to the next stage of treatment, and that is biologics. There are 2 classes of biologics that are currently available. One is the tumor necrosis factor [TNF] inhibitors, and the other one is interleukin [IL] 17 inhibitors. The tumor necrosis factors inhibitors or TNF inhibitors came into the market and got FDA approved around 2003, 2004, and they are the ones that we first use after failure of the nonsteroidal anti-inflammatory drugs and physical therapy. If using those also keeps the disease active, we can always change to another anti-TNF drug, and this is called the secondary failure. So if somebody has good response to the first anti-TNF for some time, and then they stop responding, then that’s secondary failure, and you can change to another anti-TNF drug. Whereas, if it is a primary failure that you try somebody on anti-TNF and there is no response whatsoever, in which case you can go straight to the other class of drug, which is the IL-17 inhibitor, and there are 2 of those agents currently available.
We also talk in those guidelines about the use of MRI [magnetic resonance imaging]. We talk in those guidelines about other comorbidities such as uveitis, about IBD [inflammatory bowel disease], etc. We have mentioned in those guidelines about whether to use echocardiogram because these patients can have heart involvement, whether to use osteoporosis, when to do surgery, when to send the patient for surgery, etc. So these are pretty extensive guidelines that we have produced, and the hope is using the guidelines will improve the care of the patient.
The window of opportunity is a concept that is very developed in rheumatoid arthritis, and it is well known that if you catch the patients early with rheumatoid arthritis and treat them aggressively, you’re going to prevent the damage, and the patient will remain symptom-free and damage-free. In axial spondyloarthritis, that concept is somewhat premature. We certainly know that finding the patients early and treating them aggressively improves health-related quality of life. We know that prevents disability. We know that prevents premature retirement from the workforce. We know that that will actually help the societal costs, individual costs, etc. Whether it really prevents progression of the disease and radiographic progression, as I said earlier, is more aspirational. There is a strong hint that we might be doing that by treating the patients early and aggressively with biologics, but all those data are retrospective, not prospective. Prospective data are the only way we will know for sure if there is a cause-and-effect relationship.
Currently, what we think is that if you catch the patient and treat them aggressively, it is still very good because you are reducing the patient’s misery. You are going to reduce their stiffness. You are going to diagnose them accurately. You’re also going to avoid unnecessary surgery that the patient might undergo by going to the wrong provider, and you’re going to avoid their long-term disability and their retirement from the workforce, as I said earlier.
Not all patients with nonradiographic axial spondyloarthritis progress to ankylosing spondylitis. There are several studies in the literature that have prospectively studied, and these numbers vary from 2% over 2 years, to 12% over 2 years, to up to 35% over 30 years. These are some of the numbers, depending on which study you look at. It is also known that some patients may never convert from nonradiographic to radiographic ankylosing spondylitis. Again, as I said, it doesn’t really matter because the disease burden is very similar.
There are certain risk factors that we know regarding which patients are going to convert from nonradiographic to radiographic. The first one is male sex. Males convert from nonradiographic to radiographic more. We also know that patients who smoke, patients who have active disease, and that is done by 2 ways to find out whether they’re active disease or not. One is looking at the C-reactive protein, and the second is the MRI scan of the sacroiliac joints. Patients who have high inflammatory burden on the sacroiliac joints are more likely to develop ankylosing spondylitis from nonradiographic.
Those with high C-reactive protein are more likely to progress. Male sex is another one that we know of. When it comes to x-ray progression in the spine, new development of syndesmophytes. People have also found that existing syndesmophytes are a risk factor for getting more syndesmophytes. And interestingly enough, blue-collar work compared with white-collar work is a risk factor. So extreme physical activity during your work is a risk factor for progression of the spinal ankylosing spondylitis, more syndesmophytes. That is not conversion of nonradiographic to radiographic. That’s the new bone formation in the spine.