Emerging Therapies in Spondyloarthritis
AUGUST 03, 2016
MD Magazine Staff
John D. Reveille, MD, and Philip J. Mease, MD, provide insight on the guidelines for IL-17 inhibition in ankylosing spondylitis, as well as emerging agents and ongoing studies in spondyloarthritis.
John D. Reveille, MD: The reason why using the IL-17 drugs is particularly exciting in patients with AS (ankylosing spondylitis) is that they don’t seem to be associated with the same kinds of infections that we see in patients with AS—so a person with a history of TB (tuberculosis) or the like would be a lot better off taking secukinumab. A lot of patients are very worried about this, so that’s why we are very reassuring to the patients. That would be one big thing right there. And you would be surprised how many patients are very, very worried about these infections. Although we are waiting to see further data, they may be more effective in preventing radiographic progression in AS fusion of the spine, and that, too, remains to be seen how real that is. Because if it is real, this clearly would be desirable to use earlier than later.
The American College of Rheumatology Treatment Guidelines aren’t a static process. They don’t have guidelines, and then stop, and a couple years go by and there are new guidelines. This is a continuous process that the American College of Rheumatology (ACR) is undertaking. This is in contrast to the European League against Rheumatism (EULAR), which they are meeting next week—I know because I’m on the panel—in Vienna to come up with new guidelines that will include secukinumab and the other non-TNF biologics that have come to the forefront. The ACR committee on guidelines will be continuing to assess these newer drugs as they come, so you’re not going to have to wait a few more years before this is actually done. It’s going to happen sooner than later.
Philip J. Mease, MD: We are very excited that, in the last few years, we’ve seen medicines with a different mechanism of action than anti-TNF therapy work in psoriatic arthritis and now be more commonly used. It’s very important that there be multiple options for treating patients because, ultimately, a patient may lose benefit from a medication that they’re currently taking. So, having the availability of medicines with different mechanisms of action is very important. We’ve already discussed that in relation to recently approved therapies—ustekinumab, apremilast, secukinumab—and there are more therapies coming down the pike.
For example, there’s another IL-17A inhibitor known as ixekizumab. We saw data at the recent ACR meeting that showed its efficacy in psoriatic arthritis. It has recently been approved for the treatment of psoriasis. So, we are anticipating that sometime in the future, we may see approval for ixekizumab in psoriatic arthritis. It is also being tested in ankylosing spondylitis, and so we will hope that we will see approval—if it shows good efficacy there—for ankylosing spondylitis, as well.
Ustekinumab has shown benefit in an open-label trial in ankylosing spondylitis, and now there’s a phase III trial in ankylosing spondylitis with that medication. And if the same quality of effect holds up in phase III, then we may well see approval of that medication in ankylosing spondylitis.
There’s another class of compounds coming along, which are known as JAK inhibitors. These are oral medications which are also signal transduction modulators. And we know that the JAK inhibitor tofacitinib works very well in rheumatoid arthritis. We will see data coming forward in the future on the efficacy of that drug in psoriatic arthritis, and so that, too, may become approved, eventually, in the treatment of that disease.
Also there are other JAK inhibitors that are in development. For example, baricitinib in rheumatoid arthritis has shown good effect. And so we’re likely to see other JAK inhibitors being tested in psoriatic arthritis and possibly ankylosing spondylitis, as well.
Yet another group of medicines, which are pure IL-23 inhibitors, are being developed. There are three of these—tildrakizumab, guselkumab, and risankizumab—all of which are showing efficacy in the treatment of psoriasis, and we are likely to see data in the future with these drugs in psoriatic arthritis and ankylosing spondylitis. And so these, too, may be possibilities in the future. It’s a good time for our patients in terms of having drugs available and emerging that can be efficacious in all the varied clinical domains of both psoriatic arthritis and ankylosing spondylitis, hopefully striving for a state of remission or low disease activity and with, hopefully, few side effects so that these patients can live a much more productive life.
John D. Reveille, MD: The treatment of ankylosing spondylitis, as far as the newer non-TNF agents are concerned, the only one that was approved by the FDA is secukinumab, which is an IL-17 blocker. There have been others that have gone through trials. Brodalumab went through clinical trials and was shown to be successful, but, unfortunately, was not brought forth for FDA approval because of some side effects that happened in the setting of the studies. There’s ixekizumab, which is currently in clinical trials. These all show promise for the treatment of ankylosing spondylitis and spondyloarthritis.
Only secukinumab is FDA-approved. It’s the only one that is currently available to us, but I’m sure that some of these other ones—particularly ixekizumab—will be available pretty soon. The IL-23 drugs are coming to the market a little more slowly, but there are at least two that are in clinical trials or about to enter clinical trials and that, again, look very promising as far as the future is concerned.