In this video, George Han, MD, PhD, discusses what dermatologists should consider when evaluating IL-23 inhibitors as part of the therapy plan.
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.
Dr Han: When we're thinking about choosing a medication, first we have to think about the comorbidities that our patient has, because certainly when we think about some of the things that we think about with the TNFα class, CHF, demand making diseases, there are certain patients that that's just off the table. When we start to get into the nitty‑gritty, that's where it becomes more challenging, and also more interesting at the same time, because now that we have so many options and so many medications, the key is figuring out which medication is right for which patient.
When you think about globally looking at the efficacy with this, we still do see some differences, especially when you look at PASI 100 data of complete clearance, and you'll see some stratification in the medications with risankizumab a little better than guselkumab, then in turn, having higher PASI 100 grades in tildrakizumab.
When you look at the average, mean, or median improvements on all of these medications, the average patient gets to above 90% clearer in terms of their baseline PASI going to where they are. Most of the modern medicines are clustering right around 95%, plus or minus 3% or so.
The actual difference that your average patient has when you put them on any of these medications is not that high. When you think about a landscape like that, we start to think about emphasizing other factors, such as safety, such as long‑term durability. Those are all interesting things that we should take into account, as well.
Obviously, safety is a big concern because that's often the first question we get when we talk to our patients about going on a systemic treatment for their psoriasis. They want to know about the safety. They want to know what to expect. It's nice that we can tell them to expect greater than 90% clearance on average from these medicines. Safety‑wise, we're looking at the IL‑23 class as overall, a pretty safe class. You don't have any of those major call‑outs. We think about IL‑23, the TH17, and IL‑17 pathway.
What is kind of unique to that is the idea that it seems to be the pathogenic TH17 and IL‑17 portion of that pathway that's regulated by IL‑23. You'll see some small population of IL‑17 that serves to act as modulatory. It serves some purpose other than pathogenic features, such as maintaining gut homeostasis. Those are populations that we'd rather avoid blocking if we can. We don't have to ask about inflammatory bowel disease. In fact, IL‑12/23 inhibition has been shown to ameliorate IBD, and we're starting to see some early data about IL-23 inhibitors potentially being a treatment for IBD as well. That's a nice thing to think about.
We don't have to worry so much about heart failure, about any of those other major things. There's not a lot of screening you have to do for the patients, which is nice.
You also think about the labeling requirements for monitoring. It's just tuberculosis tests for all of them. The nice thing is that, yes, from a theoretical standpoint, we have very little to worry about in terms of reactivation of TB. We feel very comfortable with this class. Even if we do get a positive screen, you just start them on treatment, and you start your psoriasis treatment, either accordingly or perhaps waiting a month. That seems to be a good strategy for those patients. We're not running into issues with that.
Similarly, when you think about hepatitis, it's not required in the label to check for hepatitis. If you are checking and you do get a positive result, let's say on a core antibody for hepatitis B, there probably isn't a lot to be concerned about. There's no reports of reactivation of that hepatitis. The only time we might get a low concern is if somehow you get a positive surface antigen, and that it indicates perhaps more recent infection, that's something you probably want to work with a gastroenterologist to getting that patient on appropriate treatment.
Thinking about that as a very narrow spectrum. It's the only thing I can think about that would preclude or prevents you from thinking about the IL‑23 class as a good first‑choice option.
When you break down the actual medications in their class—tildrakizumab, guselkumab, risankizumab—there are a couple of subtle differences. The dosing regimen is one. Risankizumab is two injections every 3 months. Guselkumab is one injection every 2 months at maintenance, and the tildrakizumab is one injection every 3 months.
The last one, tildrakizumab, is also indicated for health care practitioner injection. That means the patients should generally not be injecting themselves with it. Even though the syringe is the same as the injectable syringes that were used to for the other medications, but it's a labeling language requirement. We find that in some cases, it's a bit helpful because for especially our older patients are Medicare-age patients. It can be covered as a medical benefit. That's sometimes helpful for us as well.
In terms of looking at efficacy, as I mentioned earlier, risankizumab has the highest PASI 100 numbers, then guselkumab, a little lower than that, and then tildrakizumab, lower than that. If you look at the PASI 90 and PASI 75 cutoffs, they all fall within similar ranges. Again, if you look at the mean and median PASI improvements, they're all within 2% to 3% of each other. Not a big difference there.
Safety‑wise, we're looking at very safe medications overall, a very short lists in terms of even if you look at the label of potential concerns. Most of those concerns, especially when you look at things we see on some of them—nausea, diarrhea, injection site reactions—for the most part, there's no big callout in this class. Most of those reactions are numerically higher than placebo, but within a percent or so. Even upper respiratory infections, this class of medication, within about 2% to 5% of placebo.
We're looking at a safe cost of medications overall, which is helpful and nice to be able to tell our patients. It's something they like. The dosing regimen too, it tends to be less frequent than some of the other medications that we've talk about oftentimes.
The last piece is the durability. So far, it looks good on their ability for all of these medications. We're starting to see 5‑year data pop up for some of the IL‑23 inhibitors, and we're seeing good maintenance of efficacy out through that standpoint. We know with the long‑term experience with this, the kinematic tends to be a pretty durable mechanism of action. Those are all pluses going for the class in general.