In part 5 of this Frontline Forum, Raj Chovatiya, MD, PhD; Neal D. Bhatia, MD; Alexandra K. Golant, MD; and Brett King, MD, PhD, discuss the rapidly changing use for JAK inhibitors and other agents for atopic dermatitis.
Chovatiya: To echo both of you, it’s rare [in other circumstances] that our patients come back to us with good news that quickly. It’s usually something went wrong or you did something wrong. I’ve gotten a few of those [good news] messages where it’s really nice to hear, “You’re feeling really good really fast.” That makes you understand why you got into this in the first place. But more importantly, for people who you’ve been seeing for a long time who’ve had horrendously refractory symptoms for years and years, the types of clinical responses you can achieve are really incredible.
I want to focus in for a moment and maybe pick Neal’s brain for a second about our great crusader, again, corticosteroids—specifically, topical ruxolitinib. Can you tell me more about why you think topical ruxolitinib does such a good job [in reducing] inflammation and itch? What are some of the differences and outcomes you’ve seen in your patients? And how do you look at its use alongside…topical corticosteroids in your practice?
Bhatia: Yes. The versatility that we see now with the topical JAK inhibitors, and not just ruxolitinib, we’ve seen a couple others in trials and unfortunately, a few, who didn’t even make the numbers. But now, we’re dealing with something you can use in [difficult] areas: areas where you were thinking about tachyphylaxis, or you were worried about atrophy, areas around the eyelids, around the mouth, around intertriginous areas. And even more so, you think about the versatility of treating through the conditions, whether it be eczema or vitiligo or what have you. Even further, what came from the vehicle of a cream—what we don’t have really in a good steroid cream—is now being able to put it on areas that really don’t have a lot of epidermal change. They’re easy to apply. With steroids, again, I look at the bandage vs remedy analogy and think, “OK, we can use this only for so long.” Right? I can’t use steroids on the eyelids or the face for too long. Plus, we have so much steroid phobia that [topical JAK inhibitors] take away some of that as part of the equation. So having this in our toolbox has been definitely helpful. But, again, why this got slapped with a black box warning is a shame. But at the same time, we tell patients, “Just don’t eat it and you’ll be fine.”
Chovatiya: It actually says, “Don’t eat it” on the label, too.
Chovatiya: Actually, yeah, [that’s a reminder] for those of you [who] don’t want to read it closely…. But to add a couple of nerdier points to Neal’s discussion, if you actually take a look at the phase 3 data for topical ruxolitinib, more than 40% of patients had some type of facial involvement. So these people were studied and not screened out of the trial; we’re using it there. People had all sorts of involvement, whether it be regional involvement, the genitals, the hands, the underarms—places where we often are very limited by our choices in topical corticosteroids. And the really common question that I get asked—and since there’s no compliance officer looking at me, I can give my clinical opinion—is, Where do you put this alongside topical corticosteroids in your practice? And people often forget that there actually is a phase 2b trial where there was an active comparator of triamcinolone. And while it wasn’t as statistically direct comparison, you can get an idea where the number stack up and topical ruxolitinib did better and triamcinolone as well. They are 2 based on just the numbers, not talking about statistics.
I’m curious to hear about your practice, Neal. I’m usually thinking about its potency somewhere in that class I, II topical corticosteroid range, both in terms of speed of onset and potency.
Bhatia: Yeah, honestly, I don’t think about where would I put the clobetasol vs triamcinolone.
Chovatiya: This question comes up a lot.
Bhatia: It does, but at the same time, it’s “OK, why don’t we think about doing this every day?” Say, with your old clobetasol that’s about to expire. Put that on some troubled spots for a couple days. And then, eventually, you’ll transition off and you’ll be fine. But to your point, Raj, [I wonder] why are we still thinking about steroids in the same equations? Why are we still driving cars that are 15 years old, right? We …do things out of habit.
Bhatia: At least, maybe we can use them wisely. And that’s not a bad thing.
Chovatiya: And again, when we think about topicals…[and] orals, what is this idea of controlled or uncontrolled? If I can make a plea out there for anyone in [academia], we still don’t actually have good definitions and ideas of what control is for AD. The same [is true for] the terminology of flare: It’s not really clear what that means as well, from the patient vs physician [perspective]….We [and patients] often are looking at different things when it comes to longitudinal control. How often are you “having” exacerbations of disease? What is your itch still like at nighttime, during the daytime? Do you feel like your quality of life is improved? There is a huge relationship between itch and quality of life: how much you’re sleeping, how distracted you are, how much you’re actually excoriating your skin, and how much you feel embarrassed about wearing clothing. Can you focus on work, be productive, be an actual contributing member of society? These things all play a role. So, when it comes to assessing control and practice, there have been efforts. The Harmonizing Outcome Measures in Eczema group looked at some of these recently, and looked at the recap and the AD control tool as questionnaires you can use to see whether someone is controlled or not controlled. It’s not like you very strictly need to use any particular numbers. The plea, I think, that we would all make is just don’t fixate so much on BSA or [any] one thing, but rather just get a composite measure: Does this person seem like they’re, largely speaking, based on all these things together, pretty clear, well controlled, almost clear, pretty good control—or not? And I think then, we end up arriving at reasons why we would want to escalate therapy or not. Thoughts, Allie?
Golant: I’ll just add that I think—even based on control or even your initial treatment decisions when you’re trying to figure out if they are a topical patient, a systemic patient—quality of life plays just a huge role. I completely agree with what you said before about this obsession about 10% or more BSA. That is completely irrelevant. You can have a patient with a [BSA] of 2% with severe disease on the hands, who [is nonetheless a] severe patient and should be treated as such. So, for me, it’s quality of life. When a patient comes back and says, “I’m better, but I still am limited, I can’t do my activities, I’m not dating”—whatever it is, that’s not well controlled. If a patient comes back and tells me how well they’re sleeping, that their life’s returning to normal, I feel that gives you a good assessment of overall control. So I would highlight just asking patients about their quality of life—that is a huge factor in the decisions I make clinically for these [patients].
Chovatiya: It’s a really good point. I’m not begging people to use a dermatology life-quality index or some other tool; it’s really just that asking somebody about how this has affected their life, broadly speaking, can end up digging up data that you don’t even expect, and it can play a really important [role] in your assessment of how exactly their disease is working. I’ll punt it over to you, Neal, to give us your thoughts on quality of life in your practice. Also, I’m curious, since you’ve alluded to this before, how do you think about treatment of rescue or flares vs maintenance and chronicity, and how does this all work its way into your clinical practice?
Bhatia: I think the patient voice, first of all, is the most important voice on all of it. Getting their testimonials to get drugs covered, to get their experience, in this subjective parts of our notes—that says volumes for the progression to their improvement. So I think the use [of the patient voice] as, I hate to say, a weapon, but at least as part of our armamentarium to get drugs covered, is very critical. But, even more so, getting patients started is basically like stereo, right? You turn a couple dials, you basically have to turn some things down, but you don’t really turn anything off.
But at the same time, we tell them, OK, you’re using triamcinolone, you’re using clobetasol, using on troubled spots while these pills are kicking in, while the shots are kicking in. And then, you’ll find you won’t need them anymore. So, it’s almost like a 2- to 3-week descent of getting them what they’ve been on. But patients don’t need something for breakthrough. No drug is going to be felt, although they don’t have breakthrough. That’s important to have for them, because patients like to use their hands …to put something on, and they feel validated when they’re actually doing something to control their disease, even if they’re taking pills or using shots. So I think having something for those trouble spots, whether it be double the steroids or topical ruxolitinib or any of the inhibitors, … is still a pivotal part of their equation…, because it makes them feel like they’re still doing something.
Chovatiya: In the case of topical therapy, the point is real, right? We know that in a lot of the diseases of the skin, it makes sense to target those areas of inflammation; even skin that’s uninvolved can show signs of inflammation as well. And so, varying topical treatments is a good strategy. And with the topical ruxolitinib, we’ll stir the pot a little bit because as we know, based on the way the label is, it was studied in monotherapy, and that’s for what it’s recommended. But I’m curious to hear from our cowboy himself, Dr King: When it comes to topical ruxolitinib, how do you think about monotherapy and combination therapy in your patients and what you do in the real world?
King: As you point out, it’s another part of the label for topical ruxolitinib that is bewildering. Because there’s no AD patient on the planet who is going to … use only 1 agent.
Chovatiya: And a 60-g [tube] too, I might add.
King: Right. We all have to recognize the label. And … it really is important in this discussion to call that out because, for sure, anybody using it needs to be aware of that, too, to make a disclaimer to their patient in case they have a patient who goes home and reads the label and says, “Whoa, whoa, whoa.” And now, all of a sudden, you’re getting the MyChart message, “Wait, you told me to. But I went home and read the label and it said that this is a no-no.” So we need to acknowledge it and be aware of it. But the truth is, we don’t know exactly what goes into the minds of the people at the FDA when they’re coming up with labels and restrictions and guidance. But I think it’s just important to recognize that even conceptually, even theoretically, there’s no harm in using topical ruxolitinib together with another topical from another class of medicines or using it in combination with a biologic, dupilumab, tralokinumab or, for that matter, an oral JAK inhibitor. In so many ways, the comment that you just made—it’s a 60-g tube—limits so much in terms of exposure. Truly, as long as our patients aren’t using it as toothpaste, we can ensure safety related to the use of that medicine. So, again, I use it liberally. That was a long way of saying I use topical ruxolitinib liberally in combination with other therapies.
Chovatiya: Yes, I think that this will be one of those areas where real-world data and use patterns hopefully shift the needle a little bit, in terms of telling [patients] ….[The] number-1 question I get asked is, Can you use this in conjunction with a biologic therapy? And just like you said, there is no real theoretical reason why you can’t. It’s just simply who chose to very narrowly label this—based on exactly word for word, how the trial was studied—which is what happens all the time for other drugs, anyway. …I think in my practice, too, if you’re able to navigate some of the access issues and coverage and be able to have multiple things, …it is a nice option especially when you’re trying not to use clobetasol all the time for everything, and knowing the baggage we’ve spent the last several sessions here talking about, in terms of topical corticosteroids. Some thoughts, Allie, in terms of your real-world use of combination therapy?
Golant: Yes, I was thinking that there’s combination therapy with other topicals, and also with systemic agents like biologics. I think, unfortunately—from what’s played out in the last few months especially—is that some of that decision, especially in combination with the systemic [agents], will be driven by the insurers. They’re not seemingly wanting to cover both of these for patients, which is not surprising to me. They’re making things a little bit difficult. But from a safety perspective, I have no concerns. And from a practicality perspective, it makes a lot of sense to use these agents like this. When you have a patient who’s doing relatively well on a biologic, for example, to be able to spot-treat with something like a topical JAK inhibitor works fairly well. I just don’t know about the long-term feasibility of doing that based on an access perspective.
Chovatiya: In the last few moments we have, let’s try to wrap things up. [Given] all we’ve said today, what advice do you have for patients, caregivers, and providers for incorporating and optimizing JAK inhibitors in their topical and oral forms for the management of AD?
Bhatia: [To patients]: Don’t think about what you hear and see as opposed to what is real. Everybody is so confused about what’s on the Internet, the chat rooms, the Facebook groups, everything else that’s negative. We joked before, I want to do something natural, it’s like, yeah, your disease is natural, how’s it going, right? We need to get everyone off the ledge of “I don’t want to do this, I don’t want to do that.” Let’s get you better and see how it goes, because the worst thing that will happen with a couple days of pills is that you’ll actually stop scratching and that’s not a bad thing. And if they want to stop, they can stop. But, again, we shouldn’t be afraid of labs, we shouldn’t be afraid of the big bad black box or whatever. Because, again, …[the police won’t] come in and take your prescription pad away. It’s good to say, “Here, use this as guidance of what was.” As all 4 of us have been saying, this was the baggage that came from unfortunate patients who had a lot of comorbidities and a lot of issues and were on multiple drugs. That won’t happen to the 6-month-olds or 12-year-olds with eczema, or whoever else we’re treating with these drugs. We had to be able to use these comfortably and say, “We did what’s right for you, because this is what’s doing something to the process of what makes your disease, not just the result of what you see.”
Chovatiya: I think that’s a very nice way to put it. Any unmet needs or things that you want to see? It’s very interesting that we’ve seen such evolution in this therapeutic space with JAK inhibitors. And in many ways, given so much of this baggage, people are so quick to feel like we need to be moving on to the next thing so quickly. Even though I feel like in many ways, we’ve really just barely scratched the surface here. So any thoughts in where things should go the next few years?
King: I think that everybody will be forced to use JAK inhibitors, because they’re so broadly important across the numerous diseases that we all see every week in our clinics. So we’ll be forced to use them, and then, I think as has been pointed out a few times, you’ll do it and realize, “Geez, my patient didn’t die. They didn’t have a horrible outcome. In fact, they got better.” And that’ll give us comfort and we will use them more quickly in the next patient, and in the next patient. I really believe that the JAK inhibitors will elevate the care of our patients, as I said earlier. They’re going to force us to redefine the treatment goals for our patients. We’re going to insist more on clear or almost clear, and itch 0 to 1. And, as much as that will happen, and that’s hugely important, that will not address all of the unmet need in this space. Psoriasis has shown us that there’s room for numerous therapeutics. And so, I’m really excited about the work that’s being done and the agents that are in the pipeline. Because I think in 5 years, we’re going to be having this discussion, and it’ll be endlessly complicated, which is going to be great because it’ll mean that we’re going to be getting increasingly toward 100% of our patients better. So I’m optimistic and excited.
Chovatiya: I like the sound of what everyone is thinking, and I’ll echo it in our last minute together: It’s a really exciting time to be thinking about medical dermatology. We’re seeing so much evolution of therapy for so many different diseases that our job becomes harder, but in a great way, because we actually have things to talk about, things that we know work, and things that are targeted treatment as opposed to the same 4 immunosuppressants that we’ve used for the last century. So, the big things I’m looking forward to are, really, number 1—and this is one of the first things that we heard from the panel when Allie brought it up—is how can we start connecting the right patient to the right therapy? This is particularly [relevant] as our therapies expand and we start thinking about some of those other agents that are coming through the pipeline. So with more specific inhibition of certain cytokines, like IL-13 agents by specific molecules that are actually targeting multiple cytokines, OX40 ligand target molecules, they’re taking a look at a different T-cell mediated pathway. Other molecules are actually inhibiting different kinases and the signaling pathway, and [others are] even modulating the microbiome. So it’s really an exciting time to think about how each of these strategies might work individually and together for the right kind of patient. And bottom line, with AD, many of the difference that we’ve reported in various populations through association-based studies—whether they be through race-based analysis, ethnicity, geography—are driven largely by a combination of external factors. The external environment is so important to disease. Our trials don’t really do a good job of capturing that. And I think that’s the one big thing I hope to see: that in addition to our actual evolving therapeutic landscape and new targets, we better understand how many of these external factors—everything from social issues, as they relate to access and insurance and care, and to water, to food, to where you live and how you grew up— influences the actual presentation and course of disease. And that’s what really excites me in this discussion.
End of series
[Edited for space and clarity]