Using Topical Versus Oral JAK Inhibitors in Atopic Dermatitis

Linda Stein Gold, MD: Thus far with the JAKs, has your experience been positive? Do you feel like they're living up both orally and topically to what our expectations were? Where are they over-excelling? We talked a little bit about this. Ale, do you feel like you use them, and 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 that we shouldn't be using it with other agents. Are you doing that in real life? What's going on?

Alexandra Golant, MD: For the systemic JAKs and for systemics in general, whether you tell patients to use or to not use topicals, often people will supplement, or since systemic JAK inhibitors are so fast-acting, 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 just 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 happens so early that I don't think people are reaching to 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 will for more maintenance or proactive maintenance. The majority of time it is being used as monotherapy or on some type of alternating basis with a low-to-medium potency topical steroid.

Linda Stein Gold, MD: So you have no problem giving a patient both 2 potentially topical steroids? Raj, do you give patients more than 1 prescription?

Raj Chovatiya, MD, PhD: Yeah, sometimes you're forced to. It hurts me on the inside to contribute to polypharmacy, right? By definition, that’s 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 1 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. We always talk about this step-up additive approach; something we've been trying to talk about in addition is now a step-down simplification approach. If you're moving up to a higher step therapy, much like Ale said, even the data would reflect that you're not going to get that much of a boost from concurrent topical corticosteroid use in the case of oral JAK inhibitors. They can largely work on their own. Similarly, much as Eric very nicely put it, when you look at that phase 2 data comparing triamcinolone with topical ruxolitinib, it's really doing as if not more heavy lifting than that is. So you're probably not going to get really that much more additive benefit as well over something that's going to be maybe equally or even less potent. With many of these new medications, as we start to get familiar with them, I'm trying to work them in as monotherapy, but in the circumstances that require it, it’s OK to add on a normal topical antiinflammatory. 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 of 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 are 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 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? Ale, what do you do?

Alexandra Golant, MD: I had that same question myself when I was counseling patients on the laboratory monitoring—just kind of a 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 your 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. No one's past that second visit. But again, around week 12, we'll recheck the lipid parameters, per the label. Then, we'll do labs between every 3 and 4 months after that. Although, it's definitely still a work in progress for me. I welcome others’ input too.

Linda Stein Gold, MD: I agree with you. Eric, do you have this down to a science? What are you doing?

Eric Simpson, MD, MCR: I do not. There are some subtle differences right in the package insert. For example, in upadacitinib, they say to check lipids at 3 months, which is recommended by the FDA [United States Food and Drug Administration], and then as needed thereafter, whereas axitinib does have a small percentage of patients who can reduce platelets at 4 weeks. That's less than 5% of patients. The recommendation is that you check a CBC [complete blood count] at 4 weeks after use. I'm going to have a consensus paper on how can we just make this simpler and not worry about all the individual details? If you wanted to not do that, I like the check at 4 weeks, redo the labs at 4 weeks, and redo them at 3 months for now, and if everything's normal, we're all going to have different frequencies. We need more real data, but after 3 months, if nothing is wrong, you could go every 3 months or maybe every 6 months potentially after that. I'm happy to hear from my colleagues because this is a new area that we're talking about.

Linda Stein Gold, MD: Are you doing a baseline?

Eric Simpson, MD, MCR: Yes.

Linda Stein Gold, MD: It's interesting, because why is it not on the label to do a base? How many people walk in off the street and have abnormal panels at baseline? If you're doing a disservice, and if you don't know who the patient is when they came in, did they have a problem at baseline or not? Even though it doesn't specifically state it, that's kind of 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 Chovatiya, MD, PhD: Yeah. Some degree of hesitancy about the adoption of new therapy comes from the other stuff that you have to do aside from just prescribing...Let's hack it back to psoriasis for a second, and let's take it back to not that long ago: the days of sort of TNF [tumor necrosis factor] blockers, right? There are a lot of similar overlaps into some of the things that you're doing at initiation—some of the things you're looking at in follow-up. Many of those patterns just fell into place and became a commonplace, and people got comfortable with it. We are saying the same thing. You're 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 ruling out infectious 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 with 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 nicely said they're going to do, but I do think taking a nice big picture view of it about what else we have done with inflammatory disease over the past 2 decades will maybe make people feel like this isn't some weird foreign thing. It's 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 1 direction versus another? Eric, how do you decide?

Eric Simpson, MD, MCR: It's important for the clinicians to know that the indication has some wording in that and it makes it sound as if the indication is that if they're a systemic candidate and they were failed by at least 1 other systemic therapy, it's unclear whether they need to be failed by a biologic or any their systemic agents. As a clinician, you need to read that and then be comfortable with how you interpret that so you can defend that in your note, or if you are going to go straight to an oral JAK, for example, after a 1-week course of prednisone, and in your mind, that's trying another systemic. There might be some practice variation. But to answer your question, I'm going to see this as a potentially second-line systemic, and then it'll roll to the patient preference. There are other biologics available other than dupilumab, for example. 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 that. I'm going to let them decide.

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

Alexandra 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 because they have a wedding in 2 weeks and need to be very clear and have that quick clearance, 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 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, any special ways that you take this patient who could go on any 1 of them, a new topical JAK, new oral JAK, or biologic and make that decision.

Raj Chovatiya, MD, PhD: Yeah. I want people to get as clear as possible, get their symptoms as controlled as possible, and get them to be the best them that they can be. One-sided treatment plans oftentimes are just very difficult to follow through 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, 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 the case with oral JAK therapy, and 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: Thanks so much. This was a great overview on how to practically approach these new treatment options.

Transcript Edited for Clarity