In this video, George Han, MD, PhD, details how IL-23 plays a role in the pathogenesis of in psoriasis.
Dr Han is the assistant medical director for dermatology at Mount Sinai Health System, assistant professor and chief of teledermatology for the department of dermatology at the Icahn School of Medicine at Mount Sinai in New York City, NY.
Transcript
Dr Han: With so many biologics approved for the treatment of psoriasis, sometimes it's hard to manage and figure out exactly where each one lies, in terms of overall treatment landscape.
What's important to keep in mind is our understanding of psoriasis has evolved through the years, and now we're thinking about the central IL-23, TH17, IL-17 pathway in terms of mediating the keratinocyte activation and proliferation that we see in psoriasis. Those IL-23 inhibitors are that first step in terms of causing the clinical findings that we see in psoriasis.
There are a number of treatments that target IL-23, and they all serve to upregulate TH17 and thus IL-17. When we block those, we reduce the levels of this TH17 pathway, thereby treating the psoriasis and the over-inflammation that characterizes it. There are a number of medications that do target IL-23.
We've had a medication on the market for over 10 years now, secukinumab, which targets the common shared p40 subunit of IL-2 and [IL-]23. More recently, we've had a number of IL-23 inhibitors that all target the p19 subunit that's unique to IL-23. The idea here is that there are some theoretical risks of targeting IL-12 unnecessarily.
What we've found out is that IL-12 doesn't seem to have much to do with the pathogenesis of psoriasis itself. When we've tested mRNA from lesional versus nonlesional skin, as well as healthy controls, you'll see no signal, no difference in terms of IL-12, but you'll see much higher levels of IL-23 in the lesional psoriasis skin, supporting the idea that that seems to be the key player here in psoriasis.
What are the downsides of suppressing IL-12? There's some evidence that in terms of immune regulation, in terms of cancer regulation, there are some beneficial effects of having some IL-12 around. Meanwhile, there have been reported some effects of IL-12 in protecting against certain types of infection, including microbacterial and salmonella infection.
I will note that most of these are theoretical considerations, because in our long-term data that we have with this, that a lot of us feel very comfortable with, that hasn't borne out that we've had any major concerns on either malignancy or serious infections. It's nice to know that our newer treatments are more targeted and also more effective in general.
When you look at the IL2-3 inhibitors, and there are three on the market right now: tildrakizumab, guselkumab, and risankizumab. These all have higher levels of efficacy than the previous generation encompassing the TNF-alpha inhibitors and the IL-12/23 inhibitor, ustekinumab. They have a higher efficacy for treating plaque psoriasis.
We're starting to see some more data come out for this class of medication as well. There's a lot of benefits in thinking about the role of treating and blocking IL-23 in psoriasis.
