JAK inhibitors for the Management of Atopic Dermatitis (AD) - Episode 11

JAK Inhibitors in Clinical Practice for Atopic Dermatitis Treatment

June 1, 2022
Linda Stein Gold, MD

,
Raj Chovatiya, MD, PhD

,
Eric Simpson, MD, MCR

,
Alexandra K. Golant, MD

Experts in the management of atopic dermatitis assess the use of JAK inhibitors in clinical practice and considerations for treatment selection for patients with atopic dermatitis.

Linda Stein Gold, MD: With your experience thus far with the JAK inhibitors, has your experience been positive? Do you feel like they're living up to, both orally and topically, what our expectations were? Where are they over-excelling? We talked a little bit about itch. Alexandra, do you feel like you use them? Do you use them as monotherapy and feel that this is where they're most successful? Do you use them with steroids? Everything, especially the topicals, is studied as a monotherapy. They tell us we shouldn't be using it with other agents. Are you doing that in real life? What's going on?

Alexandra K. Golant, MD: For the systemic JAKs and for systemics in general, whether you tell patients to use or not to use topicals, often people will supplement or the systemic JAK inhibitors are so fast-acting that oftentimes the topicals get dropped quite early if they are on board at the beginning. If you look at their concomitant topical steroid data, they barely got a boost because most patients are well controlled with monotherapy use. I like to get a clean picture of what the drug is doing on its own. I usually say, “we're going to start this new medication and let it behave on its own.” The itch improvement in particular happens so early that I don't think people are reaching to the supplement with many of their topicals for the majority of patients. The topical JAK inhibitor is somewhat different and patients are not always reaching for it if they're having an acute flare, but more for maintenance or proactive maintenance. The majority of time it is being used as monotherapy or in some type of alternating basis with a low to medium potency topical steroid.

Linda Stein Gold, MD: You have no problem giving a patient both topical steroids. Raj, do you give patients more than 1 prescription potentially?

Raj J. Chovatiya, MD, PhD: Yeah, sometimes you're forced to. It hurts me on the inside to contribute to polypharmacy because by definition it is anywhere from 2 to 11 prescription medications. When you think about it as dermatologists, we're committing that cardinal sin constantly because we can't go a visit without giving 3 to 4 things. I'm as big of a culprit as they come. The nice thing about these new therapies is that we're able to simplify the regimen and we always talk about this step-up additive approach, which is something that we've been trying to talk about, that is now a step-down simplification approach. If you're moving up to a higher step therapy, the data would reflect that you're not going to get that much of a boost from concurrent topical corticosteroid use in the case when oral JAK inhibitors since they can largely work on their own. When you look at that phase 2 data compared to triamcinolone with topical ruxolitinib, it's doing more heavy lifting. You’re probably not going to get that much more additive benefit over something that’s going to be maybe as, or even less potent. With many of these new medications, as we start to get familiar, I'm trying to work them in as monotherapy, but only in the circumstances that require it to add on a normal topical anti-inflammatory. Over the course of the next year or 2, this is when most of our real-world data and reports are going to start to come out; what does a real-world prescribing pattern look like? How are people combining these therapies? How are people not following the exact indication? It's going to give us a good idea if there's any safety or efficacy signals that we just weren't clear about before.

Linda Stein Gold, MD: What has your experience been now that these drugs are available with blood monitoring? Are your patients pushing back? Do you feel like clinicians are pushing back, or do you feel like this is ok and that we can do baseline labs? Do you have an established routine at this point in terms of what you feel is the appropriate blood monitoring? Alexandra, what do you do?

Alexandra K. Golant, MD: I had that same question myself when I was counseling patients on the laboratory monitoring just out of curiosity on how it would be received. In the context of a medication that you've gone through the label with a patient on, there's some comfort that patients get in saying that there are these risks, but we are going to be doing laboratory monitoring with the exclusive goal to make sure that you're staying safe on this drug. I have not received any pushback on the laboratory monitoring. I am doing baseline labs and bringing patients back between that 4- and 6-week mark to check labs again and plan to see them once these just came out end of January. No one's at that past that second visit. But again, around week 12, we'll recheck the lipid parameters that is per the label and then we'll do labs between every three and four months after that. Though, it's definitely still a work in progress for me. I welcome others’ input, too.

Linda Stein Gold, MD: I agree with you and I'm wondering, Eric, do you have this down to a science at this point? What are you doing?

Eric Simpson, MD, MCR: I do not. There are some subtle differences right in the package insert. For example, with upadacitinib, they say to check lipids at 3 months and that's recommended from the FDA and then check as needed thereafter. Whereas axitinib does have a small percentage of patients who can reduce platelets at 4 weeks and that's less than 5% of patients. The recommendation is that you check a CBC at 4 weeks after use. I'm going to have a consensus paper of, how can we just make this simpler and not worry about all of the individual details? If you wanted to not do that, I check at 4 weeks, redo the labs at 4 weeks, and probably redo them at 3 months for now. If everything's normal, we're all going to have different frequencies and so we need more real data. After 3 months, if nothing's wrong, you could go every 3 months or maybe even every 6 months potentially after that.

Linda Stein Gold, MD: I want to come back to that and check the lipids at week 4. Are you doing a baseline?

Eric Simpson, MD, MCR: Yes.

Linda Stein Gold, MD: Why is it not in the label to do a baseline? How many people walk in and have abnormal panels at baseline? If you're doing a disservice and if you don't know who the patient is when they come in, did they have a problem at baseline or not? Even though it doesn't specifically state it, that's critical to do.

Eric Simpson, MD, MCR: I agree.

Linda Stein Gold, MD: Raj, any other thoughts on this? This is one of the things that people are going to have the most questions about. Am I doing it right? When can I stop?

Raj J. Chovatiya, MD, PhD: Yeah. Some degree of hesitancy about the adoption of a new therapy sometimes comes from the other stuff you have to do aside from just prescribing. Back to psoriasis for a second, let's take it back to not that long ago to the days of TNF blockers, right? Largely, there are a lot of similar overlaps into some of the things you're doing at initiation. Some of the things you're looking at in follow-up. Many of those patterns just fell into place, become commonplace, and people got comfortable with it. We are largely saying the same thing. You're probably going to check a little more often early and later on, you're going to check a little less often. If you just want to break it down at the beginning, you're going to do a little bit of ratters manufactures stuff and beyond that, it's going to be the kind of labs we're very used to. When you put it in a big picture like that, it's not that different from monitoring that we've become comfortable, whether it be conventional oral immunosuppressive agents, or whether it be biologic therapies for other inflammatory diseases. I don't have too many differences in terms of what everyone here has very nicely said that they're going to do, but taking a nice big picture view of it about what else have we done with inflammatory disease over the past 2 decades will maybe make people feel like this isn't some weird foreign thing. It's actually quite familiar to what we've done before.

Linda Stein Gold, MD: We have so many great choices right now, if a patient comes in and they're in that in-between category, where could we potentially use a good topical, a topical JAK, an oral JAK, or a biologic? What's going to make you decide and push you to one direction versus another. How do you decide?

Eric Simpson, MD, MCR: It's important for the clinicians to know that the indication has some wording in that. It makes it sound as if the indication is that if they're a systemic candidate and they failed at least one other systemic therapy and the wording is a little vague and it's unclear whether they need to fail a biologic or systemic agent. As a clinician, you need to read that and then, be comfortable with how you interpret that so that you can defend that in your note, or if you are going to go straight to an oral JAK, for example, after 1 week course of prednisone and in your mind, that's trying another systemic. There might be some practice variation. To answer your question, I'm going to see this as a potentially second-line systemic and then it'll roll the patient preference. There are other biologics available other than dupilumab. Do you switch to a different biologic class? Do you go straight from a traditional immunosuppressant to a JAK inhibitor? It's going to be patient preference and their risk aversion, their comorbidities, and all of that. I’m going to let that decide.

Linda Stein Gold, MD: Alexandra, do you look at it any differently?

Alexandra K. Golant, MD: No. Patients make decisions based on a whole number of factors sometimes that we can't predict. The JAK inhibitors will be that kind of second-line systemic agent, but behind what and in what order is the question. Some patients making the decision weigh the efficacy and the safety that you're telling them about may reach for a biologic first, but there are other patients who don't like the idea of doing an injection and are motivated because they have a wedding in 2 weeks and need to have that quick clearance. We use their own personal set of circumstances or preferences and make the decision that feels best for them. There is going to be a role for their usage in a whole number of different orders like just when viewing that treatment algorithm. It'll be interesting to see what we do now 3 months after and what we do 3 years from now, and how that will evolve.

Linda Stein Gold, MD: Raj, are there any special ways that you take this patient who could go on any one of them like a new topical JAK, new oral JAK, or biologic, and make that decision?

Raj J. Chovatiya, MD, PhD: Yeah. I want people to get as clear as possible, to get their symptoms as controlled as possible, and to get them to be the best “them” that they can be. But one-sided treatment plans oftentimes are very difficult to follow through with in the real world. You have to work with your patient in terms of what's going to work for them and that is largely what is going to parse out how somebody falls in terms of a topical route versus a biologic route versus an oral route. There are subtleties along the way in terms of what might be practical for them and what other comorbidities and indications might be there, particularly in the case of biologic therapy, where we're starting to see some other indications for biologic therapy that overlap with people that have atopic dermatitis, and even in the case of oral JAK therapy, where there may be other indications that overlap with individuals that have atopic dermatitis. This is going to be a time argument where this is going to largely settle out, but at this point in time, the patient voice is going to have to be paramount to the decisions that we make.

Linda Stein Gold, MD: Great. Thanks so much. This was a great overview on how to practically approach these new treatment options.

Transcript Edited for Clarity

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