Inflammatory Pathways in Spondyloarthritis

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John D. Reveille, MD, and Philip J. Mease, MD, outline the inflammatory pathways in ankylosing spondylitis and psoriatic arthritis, as well as mention the newer mechanism of action.

John D. Reveille, MD: As far as whether a mechanism of treatment outside of just blocking anti-TNF is important at this stage of the game, the answer clearly is yes because only about 60% to 70% of people in clinical trials have a meaningful response to anti-TNF agents. It’s a pretty good response rate, but that still leaves you 30% to 40% of people who are having either no response or inadequate response to these agents—and there are other pathways.

As we better understood the genetics in this disease, the genes have told us about new treatments. One axis that is very important in the inflammatory process in spondyloarthritis is the Th17 axis and drugs that target that. Tumor necrosis factor is part of that axis. But upstream away—further back in the sequence of events—you have IL-23 and IL-17 production. And we are now realizing that targeting them can have very, very good results ultimately in disease progression. In fact, in the case of IL-17, we have one drug that’s already been approved by the FDA for use in both psoriasis, as well as in ankylosing spondylitis—and it’s also been shown to be very effective in psoriatic arthritis (PsA)—and that is secukinumab, otherwise known as Cosentyx. It was approved by the FDA a year ago for psoriasis and approved back in January for psoriatic arthritis.

And phase III clinical trials have shown that blocking IL-17 is very successful, not only slowing down the inflammation that patients have with spondyloarthritis, but also in preventing radiographic progression. So, this is really very, very exciting. Again, the observational data suggest that is the same for TNF blockers, but these may even be more effective. And so it’s a very promising pathway. As other IL-17 blockers go through clinical trials and are approved—and as we begin to more specifically target IL-23—it’s a very exciting future ahead for our patients because we believe these are very effective drugs and show a lot of promise for really changing the face of this disease.

Philip J. Mease, MD: Although many patients can benefit from cycling through anti-TNF therapies, if they have loss of affect or side effects from one of the medications, there is still a problem in that, eventually, they run out of options or can’t tolerate or have safety problems with anti-TNFs. And so we definitely need to have medicines with a different mechanism of action that can be effective for treating psoriatic arthritis.

There are a number of new medications that have proven efficacy in PsA. These include apremilast, ustekinumab, and secukinumab—the most recently approved medication—and there are more on their way.