Emerging Therapies in Spondyloarthritis
APRIL 06, 2017
MD Magazine Staff
Allan Gibofsky, MD: There are a variety of inflammatory pathways that are active in ankylosing spondylitis, psoriatic arthritis, and, indeed, rheumatoid arthritis. We can’t know which one is active in any patient at any time, so our therapy for these diseases with biologic agents is often empiric. By that I mean we choose one, then another, then another, but we may not be actually targeting the cytokine or mediator of inflammation that is elevated in that patient at that point in time. We will start with the TNF (tumor necrosis factor) inhibitors in psoriatic arthritis because those are the ones we have the most experience with.
Ustekinumab is an agent that targets an interleukin (IL), another inflammatory mediator—particularly IL-12 and IL-23. It is an agent that has shown great promise in both diseases, but, if anything, probably is more effective in skin disease than joint disease. As a rheumatologist, I’m primarily interested in the joint disease. My colleagues in dermatology are interested in the skin disease. If you can get both, that’s great. But if you can get one and not the other, then the patient may be telling you that the inflammatory pathway in them may not be related to the IL-12 or IL-23 pathway that you are controlling.
There is another agent, a newer agent called secukinumab, which targets yet another interleukin, another mediator of inflammation, called IL-17. So, the pathways are multiple and they are redundant, and targeting one may not necessarily affect the other. There are agents on the horizon that are being studied, such as the JAK (janus kinase) inhibitors. These are small molecules that are given orally, unlike the biologics which are given subcutaneously or intravenously. These small molecules act upstream in the inflammatory pathway, and there are several studies which suggest that one or more of these agents may be effective in the treatment of psoriasis or psoriatic arthritis and possibly even ankylosing spondylitis as well. There are no approved agents for this class for these conditions as of yet. And the FDA still has to review all the data before they could, or should, be used in clinical practice by anyone.
There are numerous potential biomarkers that are being looked at. However, they really haven’t been studied in all patients with all forms of psoriatic arthritis and all forms of ankylosing spondylitis. There is an agent called the 14-3-3 eta, which is a serum marker which some have demonstrated to be correlated with some features and activity of the disease, but not with enough validity such that it can be used reproducibly or over time to indicate whether or not there is active control of disease activity. There are a variety of other research biomarkers that are being looked at in small populations. But at the present time, we really don’t have a good biomarker that is either predictive of the disease or correlates with disease activity such that it can be used routinely and informatively.
Transcript edited for clarity.