In recent years, several biologic therapies have been approved by the US Food and Drug Administration (FDA) for patients with plaque psoriasis. These treatments and guidance on understanding their role in patient care were discussed at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference.

Following these presentations, featured expert Steven R. Feldman, MD, PhD, was interviewed by Conference Reporter Associate Editor-in-Chief Christopher Ontiveros, PhD. Dr Feldman’s historical and clinical perspectives on biologic therapies for patients with plaque psoriasis are provided here.

Certain diseases are caused by a mutation in a single gene; psoriasis is not one of those. Over 100 genes are linked to psoriasis, so, to some extent, psoriasis is not one condition but rather a heterogeneous group of conditions brought on by different genetic predispositions. That said, several of the genes linked to psoriasis are in the same pathway—the IL-23/TYK2/IL-17 pathway. I think of psoriasis as largely being an overexpression of the IL-23/TYK2/IL-17 pathway. Having the gene alleles that cause an overproduction of this pathway leads to psoriasis; another way to look at it is that having the alleles of those genes that are not associated with psoriasis would prevent one from having psoriasis. Thus, blocking that pathway is, in many ways, “nature’s way” of treating the disease. You are getting to the root cause of the problem. Typically, when you get to the root cause of the problem, you are going to have a relatively safe and effective way of treating the disease. Several biologic and small-molecule therapies target this pathway.

As discussed in “Psoriasis Essentials: A Beginner’s Guide to Diagnosis and Management” at the SDPA 22nd Annual Fall Dermatology Conference, when the TNF inhibitor etanercept first came to the market, it was revolutionary, a quantum leap forward in our ability to safely and effectively manage psoriasis. But I almost never use it anymore, except in young children because it is one of the few treatments we have that is FDA approved for those under the age of 6. Then pharmaceutical scientists brought newer, even more effective, safer treatments to the market. When adalimumab came out, for example, it was another quantum leap forward in efficacy from etanercept, and probably just about as safe. Then ustekinumab came out, and it was probably at least as effective as adalimumab and safer. Instead of a patient needing an injection every 2 weeks with adalimumab, someone on ustekinumab needed an injection once every 3 months after the loading dose. That was like a miracle. Then IL-17 inhibitors came out that were more effective than ustekinumab, followed by IL-23 inhibitors that were probably at least, in the long run, as effective as the IL-17 inhibitors, with marginally more favorable side-effect profiles than those of IL-17 inhibitors.

For patients who prefer an oral drug over an injectable drug, the first option to become available since methotrexate, acitretin, and cyclosporine was apremilast. Although apremilast is less effective at getting patients completely clear, if a patient prefers a pill over an injectable, we can start there and then go on to an injectable if apremilast does not work. Deucravacitinib is a newer pill that is more effective than apremilast but not as effective as IL-23 blockers and probably has some increased risk of activating latent viruses. This is another option for patients who do not want an injection or for patients who try injections but find that they do not seem to work for them.

An interesting abstract at the SDPA conference presented the results of a post hoc analysis of phase 2 findings through week 52 on an oral IL-23 blocker. If you give me an oral agent that is as safe and effective as an injectable IL-23 blocker, other than a permanent cure, you may have reached the “holy grail.” And so, it is really exciting to see that researchers are working on an oral IL-23 blocker.

I am not sure that there is any one biologic that is clearly best for all patients with plaque psoriasis because different patients might rate safety vs efficacy differently. I like the IL-23 inhibitors as my starting point because they are relatively safe. You are getting to what may be the underlying cause of psoriasis when you are blocking IL-23. But IL-17 inhibitors work faster. If a patient prioritizes speed, that may be the right option for them. However, although IL-17 inhibitors are faster in head-to-head studies, they do come with some risk of inflammatory bowel disease. It is a small but real risk that should be considered in the decision on how to proceed.