In part 1 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.
Raj Chovatiya, MD, PhD: The first part of our discussion today will be talking about JAK inhibitors in the management of AD [atopic dermatitis]. This is kind of an exciting and cool topic because of how much has been happening in this space, particularly over the [past] year or two. Could we start with some of us sharing our thoughts about this rapid expansion [of] the therapeutic landscape and what this means for our patients with AD? Neal, can you start us off and tell us how you view [these changes] and what they have meant for your patients?
Neal D. Bhatia, MD, PhD: The landscape starts with what’s been done in research. Obviously, those of us who are here have talked about what we’ve seen in trials, the erasure of eczema in people, the improvement of itch within days. The understanding of this class of drug fits as opposed to steroids, shots, and everything else. I think even more so now we have a new game to play. We have to talk to patients about all you’ve heard about on the internet, all you think you know. Black box warnings are just guidance; they’re not mandates. We have to understand the differences [among] black box warnings: from what happened to patients with rheumatoid arthritis decades ago, to what are the incidences of adverse events [AEs] in the trials in patients who are 12 years and older or 18 years and older or what have you. So now we’re in discussions with patients [about] getting them on drugs and getting them better and getting them over the hurdles.
There is a little bit of challenge with the landscape, but at the same time, the competitors of these new drugs are—you know, the old way of using steroids. It’s about getting off the bad things and getting into something that’s going to be part of the sprint and the marathon.
Chovatiya: I like the way you’re describing [how we] think about a nontargeted approach vs a targeted approach and how we can integrate that in what we’re doing. Allie, can you tell us what all this hubbub over the [past] year or two has really done for your patients?
Alexandra K. Golant, MD: If you think of how we treat AD today vs how we treated it certainly 6 years ago, but even just a year, a year-and-a-half ago, the landscape has changed—significantly. In this disease we went from no options, to some options, and now many options, almost to the point where we can start asking ourselves, kind of, what drug for what patient. The more options we have to offer our patients in any disease state…helps elevate the bar of where we can get them in terms of treatment goals, in terms of clearance, especially for patients with AD. For so many decades, we were behind, relative to how we treated other inflammatory skin disease. These patients were given the same set of topicals over and over, and really we were stuck on this hamster wheel. To be able to break that experience for these patients and actually help get them better and get them to whatever the shared treatment goal is has been really rewarding.
Chovatiya: I couldn’t agree more as far as my patients go. I’ll let you get a word in here, Brett. What has everything that’s…happened over the past few years meant for your patients with AD?
Brett King, MD, PhD: For me, the introduction of the JAK inhibitors—in particular, the oral JAK inhibitors—has meant that we have to ask ourselves now more than ever before, what does good control of disease mean? In a world where we had 1 therapy…any “better” was good enough. But now, in a world where we have more than that 1 treatment, we have to ask, what is good enough? Can we or should we be striving for clear or almost clear? Should we be striving for an itch of 0, 1, 2 [on a scale of 0 to 10]? In [the] world where all we had was dupilumab, if your itch went from 10 to 7, that “better” was good enough. Now, a 7 means that we should be introducing a JAK inhibitor and trying to do better. So I think…the JAK inhibitors and, obviously, every advancement after this …[will] continue to continue to elevate the care of patients with AD.
Chovatiya: [That’s] a …nice way to think about it. [I’d like to] summarize what the group is talking about. From Neal’s perspective, [it’s]… stopping the old way of doing things. From Allie’s perspective, [it’s]… breaking that cycle that people are stuck in. And then really from your approach, Brett, thinking about how much better we can do for our patients. That being said, maybe we can just talk … about … our general approach to AD care first, and then we can … figure out how …experts like, you know, everyone around this table … approach thinking about the use of topical and oral JAK inhibitors in our patients. Allie, maybe you can take us through generally. What’s your approach to AD care? Is there …something that you think about as optimal? [Is] there guidance or factors you follow? What’s your way of doing things?
Golant: I think when we think of inflammatory skin diseasein general, patients are …[dropped into buckets] as a topical patient or a systemic patient. That question is answered by how we define moderate to severe disease in AD, and that has changed. … [I]n the past, we reserved our systemic agents for our most recalcitrant, most severe disease. And now we are able to offer them to patients who [have] uncontrolled [disease] with topicals, either by itch or skin. So, my general algorithm for a [patient with AD] …. depends on the presentation, but for the average patient, I want to ensure that they’ve tried [a regimen that has failed] with appropriate use, usually a topical regimen of a steroidal plus a nonsteroidal. [Appropriate] means not overusing a steroid, [and] things are being applied in the appropriate way. And then, after that is done, or if they’ve come to me already having done that, I usually begin a discussion about systemic options, our biologic options, or our oral JAK inhibitors, and I try to do that early. ...[It’s] important to let patients know that [they have] other options. We’ve seen so much innovation, even in our topical therapies for AD, with our new topical JAK inhibitor and others in the pipeline, that some patients don’t need to progress to systemic treatment. [Some] mild or mild-to-moderate patients can remain well controlled with topicals. But that’s generally how I approach that algorithm.
Chovatiya: That’s a nice way to think about it because with AD it’s…stepwise and additive, [which] is really what we’re usually doing. …[What’s] nice about the [current] innovation is that we’re so used to adding one therapy [to] another therapy [to] another therapy, making life so complicated for our patients. …[To] get targeted treatment on board and simplify the regimen is something that … excites me … . When making that treatment selection, it’s a balance of what you’re looking for, what the patient is looking for, [and] what the caregiver is looking for. How do you put all that in context, in terms of really making sure this is a decision that everyone’s in line with as opposed to, one might say, the old-fashioned way of medicine, where [the doctor tells] you just do this and that’s the bottom line?
King: In my mind, shared decision-making has become a popular idea…, and I think for good reason. I think that we’re becoming more mindful hopefully in medicine in general, but…in dermatology in particular, about considering patients less as … objects of our care and more as [people who have] come to see us for care. So we are going to make decisions together with them,…shar[ing] with them the myriad options that stand before them, and help them make good decisions for themselves or for their loved ones. The challenges of that are that it takes time and dermatologists often don’t have a lot of time, but it can be done. And I think that we’re doing a better job of that …. .
Chovatiya: When you think about the fact that we focus so much on efficacy and safety, and really it’s like that third part of the argument about feasibility. What will someone [adhere] to? Adherence is the big buzzword…[and] I think it is, arguably, equally important because at the end of the day, you may have a perfect plan, but if that perfect plan is something someone won’t follow, then… it’s a useless plan… . And as Alexandra was telling us before, some [patients] just really want to use topicals and some [patients] want to use systemic, [so] sometimes you’re limited in terms of what the patient will do. I’d much rather have [a patient] use something that they feel comfortable with, then work on a transition to another category if we really need to.
That…does naturally lead into [this] question: When we’re thinking about transferring between categories of treatments that we use for mild and moderate and severe, often it’s for [patients who] may not have good control. They have active symptoms, continued itch, continued dermatitis in parts of the body. Neal, maybe you can walk us through about how and when you think about altering or escalating a therapy. [The part we often] don’t think about is … that sometimes people get better and we want to downgrade therapy. [Other] times they’re getting worse and we want to upgrade therapy. How do you work through all of that?
Bhatia: It’s interesting, because we get into the discussion of process vs what’s in front of us. The analogy [I use in talking] to the patients is turning off the faucet vs mopping up the mess. You think about what [can] we do not just to stop what we have in front of us, but what are we doing to keep things going? What are we doing to…keep your itch away and make things go away quickly, but also make them stay comfortable? So, I think a lot of that, and just as we discussed about algorithm, comes to what we used to use with steroids—with prednisone, for example. All the things that we had in our toolbox, which were minimal, have now completely expanded. Obviously, shots and pills have changed the game, but we have to still remember that patients need something top down. They like to use their hands and put something on in the areas that are troublesome. But even more so, escalating therapy is almost the inverse of maybe we should be thinking because now it’s about let’s put out the fire, let’s work our way down and let’s keep things away because that may be the better approach to make patients understand the severity of where they’re at. Part of the problem, too, is maybe we underestimate efficacy because we’re so concerned about safety—like we just [mentioned] about black box warnings and everything else. [However], black box warnings are just a guidance….Nobody’s going to come in through the window with the [police] and say, “No, don’t write these drugs.” Black box warnings…. [note that] these [AEs] could happen, but patients [read] on the internet that these things [will] happen. So, we have to literally spend more time playing defense, talking them off the ledge, and saying let’s work our way through getting you better, because the way these drugs work to stop the process will be much more effective than what we’ve done [previously]. So, to think about escalating should almost be the inverse in saying, you know what, let’s start good and strong and let’s work our way down.
Chovatiya: I think what I’m hearing is the idea of …balance and not undertreating, … and I think it’s something…that we’ve all talked about…. It’s this idea that our patients are [often] undertreated, whether [it’s from]… not wanting to move from a current therapeutic option, not adopting a new therapeutic option, [or] concern about … a perceived efficacy or safety.…I think the big take-home [point] is not being afraid to escalate therapy when required because this is a chronically burdensome disease that needs … chronic treatment for many people. Particularly for those with more moderate, severe, and persistent forms of disease, you …want to make sure you’re doing right by them. That discussion of, well, when [will you] use a topical, when [will you] use an oral and biologic is tricky, because we think about these buckets of mild, moderate, and severe as if it’s so clear. But … a lot goes into that discussion.
[In terms] of trials, a lot of this is clinician-reported outcomes of an Investigator’s Global Assessment, which is a measure of general lesion severity; an [Eczema Area Severity Index] EASI score is [also] a popular one. Some [physicians] like using actual surface area, and this is all part of the discussion, but really, you have to add in those other things when it comes to symptomatic burden: itch, skin pains, sleep disturbances, …quality-of-life issues that really allow you to get a good gestalt about what severity is. I like to think about all of those factors when I’m making a determination. Is this somebody [who] would be reasonable for topical therapy? Is this somebody [who] has a reasonable amount of surface area where that could just do it? Will it be too difficult? Do we need to move up to…an oral or biologic or other type of systemic therapy to … manage things…from the top down?
And it’s funny how there’s … this obsession with body surface area [BSA]. Honestly, on behalf of the payers more than anything else, we’ve been ingrained to think about this. There’s this magical number of 10 across every disease, interestingly, that equals whether something is moderate or severe. And that’s the threshold for systemic therapy. And so anyone who [reads] this, please, that is not the cutoff for really anything other than maybe some decisions about practicality for use; rather, [you should] make a global assessment when you’re trying to make that decision. Neal, any thoughts on that?
Bhatia: …I was just laughing because we all do the research on these drugs. We’ve all had the entry criteria. We all see who’s coming, and yet now this is all being held against us. I mean, you get these high school dropouts who are running insurance panels who tell us, oh yeah, you know, they should have this much X a month. They should have this much surface there. It’s like, where did you get these numbers from?...You don’t know what you’re talking about.
But at the same time, we all really are investigators/clinicians, and no matter what practice model we have, [we] should still be able to say, you know what, I walk in the room and [I see that] you’re severe, [or I see that] you’re moderate, [or I see that] now, today, after, 6 weeks of treatment, you’re mild. That’s an assessment that should be in the chart. An EASI score is not that difficult to put in the medical record. But at the same time, these are objective measures that we like to use to stratify patients. [We] say, OK, we know how bad you are, and yet here’s the objective translation to it. But now it’s being held against us to write the drugs that we know [will] work, so it’s definitely a double-edged sword.
[Edited for space and clarity].