Off-label use of JAK inhibitors can prove beneficial in the treatment of several dermatologic conditions.
Casey Butrus, PharmD: 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?
Brian Keegan, MD, PhD: 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.
Michael Cameron, MD, FAAD: 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.
Amy Brennan: 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.
Casey Butrus, PharmD: 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.
Amy Brennan: 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.
Brian Keegan, MD, PhD: 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.
Casey Butrus, PharmD: 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?
Michael Cameron, MD, FAAD: 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.
Casey Butrus, PharmD: 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?
Michael Cameron, MD, FAAD: 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.
Casey Butrus, PharmD: 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.
Transcript edited for clarity.