Expert Perspectives on the Management of Plaque Psoriasis - Episode 3

Mechanism of Action of Biologics Used in Plaque Psoriasis

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Jerry Bagel, MD, MS, discusses the mechanism of action of biologics used in plaque psoriasis.

Alexa Hetzel, MS, PA-C: When we talk about all these different treatment options, what are the mechanisms of action of the options we have?

Jerry Bagel, MD, MS: We’re going back in time, and we still have tumor necrosis factors [TNFs]. Tumor necrosis factors are all biologics, which are tumor necrosis factor inhibitors. Essentially, they bind tumor necrosis factor that’s produced by T-helper 1 cells. TNF induces the proliferation of epidermal cells. It opens the blood vessels so more T cells can get down to lymph nodes, and it facilitates T cells into the lymph vessels and into the blood, so it happens a lot more. It’s not very selective.

Then we had ustekinumab and IL-12, IL-23, which inhibits T-helper 1 and T-helper 17 cells. We found out that it worked well, but when you inhibited TNF, you inhibited IL-17. We found out that we didn’t need to inhibit TNF. By not knocking out Th1, the medications became much safer because we still had TNF, which helps fight viruses and tuberculosis and decreases malignancy. We had a lot safer drugs going forward with the IL-17s. The IL-17s are interesting and block IL-17, which induces proliferation of the epidermal cells. But blocking them and their IL-17 is like in the neutrophils or the epidermis in the T cells, because you’re blocking it from lots of places and they’re quite effective.

Most recently with the IL-23s, all they’re doing is stopping the proliferation of T-helper 17 cells, which stops IL-17. Therefore, you stop that IL-17 from inducing the epidermal cells from proliferating, but it’s much more selective. By being much more selective, it’s also safer. We have developed from when I started in residency and people were in the hospital for 1 month at a time getting tar baths and tar ointments on them every day and increasing doses of light. After a month of going home only to come back for the same treatment a year later, we have advanced from that to the IL-23s, where 4 shots a year clear 60% of everybody as a long distance.

Alexa Hetzel, MS, PA-C: It’s pretty great that we get to be overachievers.

Transcript Edited for Clarity