Brian Keegan, MD, PhD

Dr Keegan, what are some patient-specific characteristics that you consider when you’re choosing an agent or a regimen for atopic dermatitis?

One of the first criteria one would want to think about is what’s the age of the patient? How severe is their condition? What have they tried before, etc.? Things like that are all important criteria, and they can range from it’s the first time a patient’s ever come in and they just need some education about what things can be helpful, and what things they should be staying away from to here are topical medicines to try, if this is just going to be intermittent, and let me know how things go to I’ve already failed this and I failed that before to the I come with a grocery bag full of tubes and creams that have a variety of prescriptions that are inside of them and a whole litany of over-the-counter medicines. Then putting the bottles in my face, “Is this one OK? Is this one OK?” Me just trying to be able to move through the conversation with them in order to get down to the nuts and bolts of what’s going on. There’s definitely a range of patients and a range of patient ages.

Then you just mentioned, we were just discussing the concept of killing 2 birds with 1 stone. So what other concurrent medical conditions do they have that they might potentially benefit from? They make a decision, back again, Dupixent [dupilumab], and someone who has asthma and atopic dermatitis, can they benefit from 1 medicine that will treat both things? Both from the simplicity for the patient, cost for the insurance company, and the mitigation of risk from the perspective of prescribing the medicines vs maybe 2 medicines where we don’t always know what the risk is when we’re combining those 2 medicines together. We just have theoretical concepts of how it might work, so that may be criteria. And then, as I mentioned before, sometimes one of the biggest challenges that patients have is they say they want something, but they really want to get better, and they may sidestep us and say that they want something else or, “I’d like just this type of a medicine because my friend told me this cream is really great.” You look at it and you’re like, “But you’ve got 3 tubes of it already in that grocery bag there that you’ve given me, and that’s really not going to make a lot of progress for you.” So sometimes what buy-in can you get from patients?

I don’t want to say that I always let them make the decision about what they’re going to give, but I’ve had plenty of patients that come in and say, “My sister takes this and she’s doing great. My aunt is on this medicine and doing great,” and if I have 3 or 4 medicines in my mind that are potentials, and they lock in on 1 of them and have a positive experience before they’ve even come in the door to me, that might be enough to try, for me to help them get over the hump of getting started on a medicine, whether it’s topic or systemic. Whatever it can take to help them get onto that next step and get better would be something that I would latch on to and use to my advantage as well too. So those are a couple of them. I’m sure Dr Cameron has a few more strategies or thoughts.

I thought that was really well said. I think that clearly a patient’s perception before they come in the office is huge. There’s a reason why…

What commercial did you see on TV last night?

There’s a reason why direct-to-consumer advertising plays such an important role still. And so clearly, if there are a couple of good options, patient satisfaction is always a priority for me as well as building trust. If they come in and they want to try therapy, if I let them try that therapy, if it doesn’t work, they trust me even more, and so it’s all about just building that physician-patient relationship. In terms of your thinking about which treatments, I completely agree. I think that a lot of times we have several good options now, which is great.

Jumping back on that direct-to-consumer advertising, I think one of the things that we should all recognize is that all these medicines that we’ve talked about today are made-up words. Opzelura [ruxolitinib], Dupixent, dupilumab, these are all made-up words, and we in healthcare are really used to using those made-up words and they make up our own language. We use a lot of made-up words all day long, and patients, when they hear those made-up words in the commercials, they can’t always differentiate them, so they may come to me sometimes with concern. 

“I want to put you on Dupixent,” and they’ll say, “I don’t want to go on that. I heard that I’m going to have a heart attack and get cancer.” And I love it when they tell me what they’re thinking because then I’m thinking, “Oh my gosh, that’s not actually anywhere in the package insert and nothing that we have to be concerned about.” But when they voice their concerns for maybe another commercial that they’ve heard and aren’t really sure of what that medicine is, we can help them to navigate that foreign language that is medicine.

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Drs Keegan and Cameron discuss patient-specific considerations for selecting optimal atopic dermatitis treatment strategies.

Patient-Specific Characteristics Driving AD Treatment Regimen

I wanted to bring back up the mechanism of action of the topical JAK [Janus kinase] inhibitor. Do you see this being beneficial for other dermatological conditions, specifically inflammatory dermatological conditions?

I have to defer to Dr Cameron. I don’t have a lot of experience with using it in a lot of other off-label conditions, so I don’t know that I’m the best person to answer that question.

For Opzelura [ruxolitinib], obviously it now has the approval for vitiligo, which is exciting. And I will add that it doesn’t have that intermittent requirement, which also adds to the whole what are we doing here thing. The vitiligo patients can continue to put it on forever, but the eczema patients can’t, so interesting. But anyways, we’re using it for vitiligo and I’m having great success with that. Oral JAK inhibitors, certainly I’ve used a lot off-label and that’s my area of focus research wise. I’ve used them off-label for granulomatous diseases, and so sarcoidosis, diffuse granuloma annulare, and for widespread vitiligo, I’ve used it as well. Rinvoq [upadacitinib] is in phase 3 trials for vitiligo. I’ve had a couple of really remarkable successes using Rinvoq off-label in patients with vitiligo. And then obviously for alopecia areata we have JAK inhibitors being used now as well.

I really do think JAK inhibitors are going to change the way dermatology is practiced. They just work for so many different things. And so, I have no doubt that, I guess your specific question was about Opzelura. I have not used that that much for other things, but I have no doubt given its mechanism of action that it would probably work for a lichen planus or a psoriasis or something like that. I don’t think that the company is exploiting those indications currently. But unfortunately, I had no luck using it off-label for alopecia areata. I found that the topical JAK inhibitor just wasn’t getting deep enough to affect the hair follicle. I’ve had to use the oral JAK inhibitor for that.

I think that is definitely one of the most difficult aspects of this job in regard to obtaining medications for off-label use. It is definitely easier for commercially insured patients where you can go through that exception process, that appeal process, letter of medical necessity, and peer review, especially if you have peer-reviewed studies and articles and things like that to support the reasoning why you’re prescribing off-label. It can get a little bit tougher for your Medicare patients, your federally funded insurance plans, and things like that because usually they are limited to only approving or covering things, specifically on label.

I know from the health plan perspective, we do have these frequent flyer drugs that we do get a lot of off-label requests for, and that’s always a question we get from our medical directors is, what is the evidence behind this? Why are we seeing so many off-label requests? And what are your thoughts on potentially approving these? And essentially, as you mentioned, the peer-to-peer process, having that provider-to-provider conversation, really sharing the data can potentially have off-label as an avenue for some patients. But it’s definitely inconsistent between payers and even between who are reviewing the case. Seeing if there’s a streamlined process that can allow for these approvals if they are medically necessary to happen is definitely something I think health plans are starting to look at.

I think it would be interesting to see because, like you said, I have seen payers where they will approve off-label all the time because they’re seeing those cases a lot and they’re learning from that. So they’re putting those specific criteria in place that are behind the scenes where when you’re requesting it for this diagnosis, they then just ask you some further questions and they can easily approve it. It would be interesting to see how much they learn from us requesting off-label drugs and how much they would evolve and adapt to that.

Well, for some disease states, there are no on-label drugs. Period. And so, I’ve gotten some medicines that have been bounced back because it’s off-label, which leads me to shrug my shoulders and say, “There’s nothing that’s unlabeled.” Then that is going to ultimately lead to another set of conversations and questions. And from the prescriber’s perspective, those can be a challenge because they can be quite time-consuming and/or challenging to be able to coordinate when I am available, when it’s a medical director available, and when can we get together on a phone call conversation in order to be able to have something happen, can be a real challenge in the office perspective.

I wanted to bring back a point of conversation about combination therapy. Dr Cameron, I know you mentioned topical ruxolitinib really isn’t recommended to be used with Dupixent [dupilumab]. Where do you see combination therapy with these new topicals coming into the biologic space, and how do you plan to manage these patients that may require both mechanisms of action?

I think the challenge is getting Opzelura approved in that Dupixent population, but we really need it. I mean, again, when you look at the EASI [Eczema Area and Severity Index] 100 rates for Dupixent or the oral JAK inhibitors, most of these patients need a topical as the bottom line, and a lot of them need it throughout their disease, not just start and stop. For that reason, ideally, they would not be using a topical steroid, from my perspective. Because I’ve seen too many untoward effects from chronic topical steroid use. For me, that’s where Opzelura comes in.

But then also I’m really excited about Vtama [tapinarof] and Zoryve [roflumilast] coming to get approved soon for atopic dermatitis as well because I think hopefully those will be approved across the disease spectrum, so across disease severities hopefully, but we’ll have to see what labeling they get. They can be used chronically, and they’re once-daily therapies and not twice daily. I think those are going to be used a lot in conjunction with Dupixent because I don’t think that they’re going to have that language saying, “Not recommended with use with Dupixent.” So I’m not sure if that’s going to be a way for them to prevent it being used together.

I know some health plans and insurance payers have language in their prior authorization that preventions the use of maybe a DMARD [disease modifying anti-rheumatic drugs] with another biologic agent. What are your thoughts? I know atopic dermatitis is an inflammatory condition, so you may see it with other inflammatory diseases like Crohn disease or ulcerative colitis. If you have a patient on one biologic like Humira [adalimumab], but you’re also considering prescribing Dupixent for their atopic dermatitis, are you comfortable with 2 biologics at once? Or do you try to find an alternative method to manage these patients?

We definitely try to find an alternative method. I do have a couple [of] patients that are on something like Humira, as well as Dupixent, but it’s certainly not ideal. That’s when I turned to something like Rinvoq, for example, an oral JAK inhibitor. I had a patient just recently that came to New York to see us, that had Crohn disease as well as atopic dermatitis, and we were able to switch him over to Rinvoq, which is approved both for Crohn disease and atopic dermatitis, and they’re doing quite well, and so killing 2 birds with 1 stone there. We always are trying to look for 1 therapy, but certainly, sometimes you may need to use 2 biologics. I know that can get quite expensive and sometimes it’s not sustainable, but sometimes we have to do it.

I like the 2 birds with 1 stone analogy. I think as these drugs are getting more and more expanded indications, even in the inflammatory space, I think that’s definitely going to be an area insurance payers are looking at to see if we can we consolidate therapy, rather than having, like you mentioned, 2 biologics at 1 time, which can be double the cost potentially for us, and for the patient having to pay 2 copays, too.

Off-label use of JAK inhibitors can prove beneficial in the treatment of several dermatologic conditions.

Brian Keegan, MD, PhD

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