MOAs of Biologics for PsA Management

Anthony M. Turkiewicz, MD: Sheetal, looking at some of the MOAs [mechanisms of action], and again, this could be a couple of days’ topic in itself, but we know there are a number of mechanisms of action available, this boom that happened. We were excited with the emergence of TNFs [tumor necrosis factor inhibitors]. This was right when I was finishing up and heading into fellowship. Now we have seen this surge of other MOAs. Beyond the TNF inhibitors, we know about the interleukin-17A inhibitors, the IL-23 [interleukin-23] inhibitors, and IL-12/23. Briefly, can you go over some of those MOAs for what’s available in the biologics here for PsA [psoriatic arthritis]?

Sheetal Desai, MD: Yes. We’ve come a long way with psoriatic arthritis, ever since it was first recognized as a separate and distinct clinical entity back in the 1960s. There have been multiple key cytokines that have been involved in psoriatic arthritis, and they’ve paved the pathway for a lot of these novel therapeutics. When I explain this to fellows and patients, I’ll say in the early 2000s, there was a bigger emphasis on the TNF family and blocking tumor necrosis factor alpha, which is the pivotal cytokine for inflammation and proliferation in the synovium in the skin, enthesitis, dactylitis. All 5 agents in this class are FDA approved for psoriatic arthritis.

In 2005 we had a novel new cytokine that was discovered, interleukin-23, a member of the interleukin-12 family because it shares the same p40 subunit.As interleukin-23 was elucidated and studied, it was known that it amplified the proliferation and survival of a whole new class of T cells, the T-helper 17 cells, which secrete interleukin-17. In this era of pharmacologic development, interleukin-23 is felt to be the master cytokine for the entire inflammatory pathway in our patients. Since 2013, we’ve had ustekinumab, which is the interleukin-12/23 blocker that was approved for psoriatic arthritis. Then between 2015 and 2020, the majority of the agents that are hitting the market are along this same pathophysiology, with interleukin-17 cytokine inhibitors secukinumab and ixekizumab. And the most recent kid on the block for psoriatic arthritis that was approved in 2020 was the first monoclonal antibody against interleukin-23, with guselkumab.

So, the top agents that we tend to use in psoriatic disease and psoriatic arthritis are historically the anti-TNF family, in which we have 5 agents. But now there are the interleukin-17 cytokine blockers, which we have 2 now FDA approved for psoriatic arthritis. We have an interleukin-23 agent that is FDA approved for psoriatic arthritis, and an interleukin-12/23 agent. This is the path that we’re going down for treatment of psoriatic arthritis and disease.

Transcript Edited for Clarity