Treatment Considerations for IL-23 Inhibitors

Transcript:

Brad Glick, DO, MPH:Neal, what’s been your experience with interleukin-23 blockers?

Neal Bhatia, MD: I brought up who my preferred populations are. There’s a downside of 23s. They may not provide rapid response to some degree; they may be a bit of a slow starter in comparison with 17s. You don’t have the frequency of doses like with anti TNFs [tumor necrosis factors]. There may be a little of that, but to be honest, I don’t think it’s much. The patients who receive them see results pretty quickly, sometimes even after just 1 or 2 doses. There’s some strong encouragement from what we’ve been seeing with this class of drugs in terms of getting patients better, not just quickly but, as Erin was just saying, staying better. Recapture data are huge. It’s a matter of saying, “This could be the 1 thing that keeps you out of your own jail if we do this right.” I’ve found this to be the class of drugs—especially when thinking about the process—that I turn to more exclusively. I’m not a huge biologics writer by any means. We run more of a trials-based practice than an outpatient practice, but for the few outpatient-practice patients we see, this is the class of drugs we primarily turn to. We’re fortunate because in California the coverage of this class of drugs is also favorable.

Erin Boh, MD, PhD, FAAD: I’d like to point out—I don’t know if you’ve all seen this; I write a ton of these drugs, so I can tell you. The arthritis response, I find in my experience, is a little slower. I talk to patients. If they have a component of arthritis, a TNF is not on board for them. If they have extensive skin disease, then the TNFs often fall short. I caution patients because I don’t see the brisk response to this arthritis that you’d see with the TNFs, but many of the patients on the IL-23s do catch up in terms of response to their arthritis amphicytes. It takes several months. I like to tell people that so they don’t jump ship too early. Sometimes I’ll use it in combination with a low dose of methotrexate. I know that’s off-label for some things. I’ll even use some of the small molecular weights while I’m waiting for the effect to kick in with the arthritis. I’d be interested to hear your thoughts on that.

Brad Glick, DO, MPH:The methotrexate was used across the board in all the psoriatic arthritis trials, even in KEEPsAKE 1 and KEEPsAKE2, and some of the other trials that haven’t been completed. Obviously, we have 1 of the interleukin-23 blockers approved for psoriatic arthritis. George, what about your comments? We’re segueing from what Erin just said, which included some great comments.

George Han, MD, PhD: I agree completely. Where I might pause a little in thinking about reaching for an IL-23 first is in that patient with severe joint disease. A couple things. We just haven’t had as much time and experience with these. That means something when you’re dealing with a destructive arthropathy, rather than something we can see a little more clearly. More than that, there was a phase 2 trial of risankizumab on actionable disease that was quite a miss. We’ve had this concept with certain IL-23 inhibitors for some reason, and it’s not well explained. Guselkumab does have some data looking at patient-reported outcomes in actual disease that seemed to imply that there’s some efficacy. That’s 1 area in which I’m looking for more data: actual disease. There’s also heavy-duty psoriatic arthritis. For most patients, those who have some vague joint pains or those you’re starting to see with 1 or 2 joints affected, I wouldn’t hesitate to reach for this. I’d tell them to wait a little longer to see the efficacy, but it's a very well-rounded class of medicines that have been pretty easy to give, stomach, and accept.

Brad Glick, DO, MPH:George, in keeping with that, in your experience, have you switched within the class of interleukin-23s? Have you had to do that?

George Han, MD, PhD: I’ll put out the caveat that we don’t know why, necessarily, patients fail on a certain biologic. That’s an area we’re very interested in. There’s a lot of active research going on, and I’m involved in some of it. That’s exciting because traditionally, what we think about is antibody formation, and we think about mechanisms that we can explain well. In some cases, it probably is that way. There’s some correlation between antibody and reduction of response, but I have these patients who get better on any biologic. And after 6 months to a year and a half, they start having the psoriasis come back in a very real way. You start to wonder what immunological escape mechanism they have, or you wonder about the lack of propensity. You might have an antibody response. It’s hard to explain. I’d like to see more data. I can’t think of anybody who I switched from a 23 to another 23. We do have data from the NAVIGATE trial, in which we look at switches from ustekinumab, a 23 inhibitor, to guselkumab. You do see that you can pick up some of the nonresponders or partial responders with that mechanism, so there’s probably some element of strength to that medication. To that end, you might reach for 1 of the medicines that has a higher, PASI [Psoriasis Area and Severity Index] 100 range if you’re looking to switch. I find, more often, I’m switching from an IL-23 class, because the patients have some breakthrough joint pain or something else where you have more of a clear route toward TNF or IL-17 inhibition.

Brad Glick, DO, MPH:Erin, do you feel the same way?

Erin Boh, MD, PhD, FAAD: I’ve switched. I do class switching sometimes. I don’t particularly like to, but in some cases I’m forced to. Sometimes, the insurance coverage says, “This is the IL-23 du jour, and you must do it.” Otherwise it’s not covered. I’ve had some patients who’ve failed to respond or maintain that 8-week or even 12-week response, so they’re going at every 6 weeks. I’ve switched them, and I find that, like the TNFs, you can switch classes and sometimes gain a response where you couldn’t before. Why? I don’t know. George, your speculation is as good as any. It’s going to come back to the genetics—maybe there’s a bit of nuance in the genes that are overexpressed, and there’s not just 1 IL-23 gene. These particular drugs will target certain IL-23 molecules and maybe a patient has a different 1, but I’ve been successful in switching out classes. In general, like George, if I find that they’re not going long enough or keeping their response, or they develop arthritis, I’m going back to something else, or I’ll add a small molecular weight that I can get covered.

In the past year, I’ve done a lot with the JAK inhibitors with the IL-23s, and that combination is a knockout. It does very well when you can’t get a full response with the IL-23. It’s not going to be covered easily, I can tell you, but we’ve worked it where we can cover some of it. If it’s not covered for arthritis, I can get the small molecular weight JAK inhibitor for the arthritis and use the IL-23 for the skin because the JAKs aren’t quite as good for extensive psoriasis. I think you can switch in the class. I don’t like to because the more you switch, inherently, you do lose efficacy. But I’d like to see, like George, why some patients lose efficacy with every drug they’re on, regardless of the class. I can’t explain it. I have no clue.

Brad Glick, DO, MPH:Neal, what’s your barometer for shifting from 1 class to another? How long do you wait?

Neal Bhatia, MD: All 3 of you brought up good points about when you switch, when you want to do that, and when you see the breakthrough of first-line things going sideways. Let’s be honest too: not every biologic is going to meet the trial end point for clearance. You’re going to get people who fail. I like Erin’s idea with the JAK inhibitors. I think of those as the sprint for some of these patients, to get them clear after what we’re seeing some of the tyrosine kinase do, molecule with some of the others. If we have patients on autopilot with 1 of the 23s and they start to breakthrough, we may switch them over to 1 of the JAK inhibitors. We can put out the fire and then reestablish biologics for the next set of years. There could be a different rotation of therapies that we could find that would affect both parts of the equation if we are talking about skin and joints, especially in terms of the comorbidities. We’re at least encompassing the entire process and not what’s outside. There are a lot of ways to spin it, but you want to be safe and get the right labs—for TB [tuberculosis test], of course—and everything else that goes with safety. Obviously, it must be tangible, but we’re learning new ways to make that work. There are a lot of ways to make that happen.

Erin Boh, MD, PhD, FAAD: One thing to remember is not to give it up too soon because patients will flare regardless. Before I switch out drugs, I search for triggers: a concomitant infection, a flare of a comorbidity, a contact dermatitis or any kind of trigger that will flare the psoriasis. I try to salvage the drug first and then switch if I really need to.

Neal Bhatia, MD: That happened to me with 1 patient. We were doing great, and suddenly she started taking beta-blockers for anxiety. I said, “Wait a minute. We didn’t talk about this.” Suddenly, there you go. Sometimes that’s all it takes.

Erin Boh, MD, PhD, FAAD: That’s the easy fix.

Brad Glick, DO, MPH: If you’ve enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your in-box. Thank you, everyone.

Transcript edited for clarity.