Casey Butrus, PharmD: I know we’re talking a lot about topical ruxolitinib, or Opzelura, which is a Janus kinase [JAK] inhibitor. How does this mechanism of action really differ from what else is on the market and even the other novel topical agent Eucrisa [crisaborole]?

Brian Keegan, MD, PhD: I think if I understand your question correctly, we talked a bit about steroids, but there are several other, probably 3 other, nonsteroidal anti-inflammatories we would think about. We talked about the names before being tacrolimus, pimecrolimus [Elidel], and crisaborole. And my understanding of those molecules is that they’re thought to work through the NFAT [Nuclear Factor of Activated T Cells] pathway of anti-inflammatory in a similar mechanism to something like say oral cyclosporine would work. And they can be effective. But as was noted earlier, the effectiveness they have can be limited. I think most people don’t think of them being even as effective as some of the stronger class 3, 2, and 1 topical steroids.

One of the classic complications that we run into with them is burning, and stinging can be a challenge. So the desired areas that we had hoped to use those molecules in initially, where we would have reduced thinning of the skin—usage on the face, uses in the axial, usage in the groin—juxtapose with the burning and stinging someone feels when they put something on their eyelids or in their armpits can be a difficult sales pitch for the prescriber when they’re in the office. When we had samples, we applied them to patients before they left the office, but sometimes they were crying before they even hit the front desk and you knew you had to come up with another plan. Unfortunately, even before that point. So there are a number of different molecules that have some potential advantages but also challenges as well.

Casey Butrus, PharmD: Yeah. I think the sensitive skin areas, like you mentioned, under the arms, behind the knees, eyelids, really want to avoid using the topical corticosteroids on the face especially. I think it’s good that we have these alternative mechanisms of action that aren’t going to thin the skin and provide patients with the relief that they need. I know you mentioned the black box warning for the JAK inhibitors before. What are your thoughts on the black box warning for topical ruxolitinib since it's a topical medication?

Michael Cameron, MD, FAAD: No, respectfully I disagree with the box warning for topical ruxolitinib and, frankly, with JAK inhibitors as a whole. I think the boxed warning is thoroughly misunderstood. And so the trial oral surveillance for tofacitinib [Xeljanz] in my opinion was a trial that was basically designed to fail. They took a really high-risk population. Everyone was over 50 years old. They had rheumatoid arthritis [RA]. They had at least 1 cardiovascular risk factor. All of them were on methotrexate with a median dose of 17 mg, 60% were on chronic prednisone, and 40% were chronic smokers. So they took this really enriched high-risk population and compared it against Humira [adalimumab], which is cardioprotective in the RA population. So a pretty tough comparison.

And even with that all being said, I’m not sure if many of my dermatology colleagues understand how minimal the incremental increased risk is even in that high-risk population. When you look at clots, for example, the number needed to harm was over 800 patients when they looked at oral surveillance. And so, if it’s over 800 patients required for one more event compared to Humira, what does that number needed to harm for a 16-year-old with atopic dermatitis [AD] that does not have any of those issues? I would argue that it’s nonexistent, basically. And so, I have over 100 people on JAK inhibitors, and I’ve had 0 safety issues. And so, I love JAK inhibitors.

In terms of topical JAK inhibitors with Opzelura, look, it’s a highly absorbed molecule. When you look at something like tapinarof [Vtama], it doesn’t get absorbed. It’s picograms. And so, the FDA was like, look, if they’re putting this all over their body, that they are going to get oral ruxolitinib dosing essentially. And so, the FDA decided to move forward with a boxed warning. But I have to say my experience with Opzelura has been incredible. It’s a highly elegant cream. It has no local tolerability issues. I’ve never heard of a single person telling me it burns. And it’s just extremely efficacious. I mean, if you think about it, it’s really hitting all the cytokines that we know are important in AD. It hits IL [interleukin]-31, which is our itch cytokine. It hits thymic stromal lymphopoietin, IL-4 and IL-13, and IL-22. And so, it’s perfect for AD, to be honest with you, and I’ve had a great experience with it. So, yes.

Brian Keegan, MD, PhD: I think Dr Cameron did a wonderful job of explaining the black box warning. I appreciate you doing that. And then I would have my backup moment and say that I think that one of the challenges is that the lay population doesn’t really understand what any of that means, but yet we have to deal with that. And perhaps, as I agree with Dr Cameron, that maybe the warnings were a touch overstated. But if one truly understands what it is, if you have a very specific population that you mentioned, perhaps that might not be the best medicine for them. But as you mentioned, for the average 16-year-old that walks into the office, they’re going to meet none of those criteria. And that’s not concerning.

But the average family that goes home and looks that information up on the internet they don’t have the educational background to be able to have to make that decision and understand, and all it does is just create a lot of fear and anxiety for them. And quite honestly, they’re worried about what will happen if they use the medicine, and we who are taking care of the patients worry about what will happen if they don’t use medicines. How will their disease continue to be negatively affected? It’s a balancing act every time we offer treatment to patients, and we have to balance out, is this going to be a more beneficial risk? And I think what you very elegantly said for 99%, and maybe even a higher percentage of the population, they would definitely benefit from it. If you have that super subset of patients that wouldn’t, will steer clear of that 0.1% of patients and say that may be at more risk.

Michael Cameron, MD, FAAD: I think that’s well said, Dr Keegan. And I think it’s our job to try to translate what I said into a lay person’s terms and speak to them about it. And so, for me, my counseling on JAK inhibitors is only a few minutes now, and it’s 5 sentences. And I’m not going to say to them, “All right now,” but I will say that my first sentence is, “This medication is a molecule called a JAK inhibitor.” And we’ve had these in rheumatoid arthritis for over 10 years. And so, I think you need to establish the legacy of these. And these are not experimental. Clearly, if you walk into the room and say, “Yes, this is a JAK inhibitor. It has a box warning, and it might kill you.” Like, no one’s going to take it, right? But I don’t think that’s a fair and balanced way to describe these therapies. And so, I think it’s our job to try to package it and give it to them in a fair and balanced way. These risks are possible, but for you, I think they’re fairly low.

Brian Keegan, MD, PhD: I think you did a beautiful job of stating that as well. And I think that both of us spend a lot of time doing peer education with our colleagues, and we both understand that what has to happen first is the prescriber has to feel comfortable with the data. And so, it does take a little bit of time when a medicine is new in order to really dig in and understand what are the pluses and minuses of this particular medicine. How is my patient going to benefit from it? What things do I need to talk with them about? Amy’s component, are we going to be able to get the medicine at the end of the day? These are all different kinds of questions that all of us have to deal with.

And to follow up on your comment, say that patients like kindergartners, they can smell fear. And when the prescriber says you did and halfhearted, I don’t know when you’re given the body language of, I don’t really know about this. And the patients can pick right up on that, and they can tell that you don’t feel comfortable with it. So, step 1 is getting prescribers to feel comfortable with what they’re prescribing and then be able to then project that onto patients and have them understand, “No. I think the benefits are going to far outweigh the risks for you. And that’s why I think this is a great medicine for you.” And I agree with you. When you understand the data, you do it in 5 sentences. We’re not going to compare, but I think I probably do it in 2 or 3, but maybe I’m not as successful as you.

Amy Brennan: I feel like that’s a big part of this landscape and the burden of access is education to the patients and explaining to them why you’re choosing the drug that you’re choosing, and so that they will go to fill that drug because you want them to start the therapy and then you want them to continue to stay on the therapy. I think a key component is them taking that first step to try to fill the drug, and then that’s when we can find out whether it’s accessible through their insurance or not and work through those next steps.

Casey Butrus, PharmD: I agree. I think definitely shared decision-making between the provider and the patient. As we mentioned before, meeting the patient where they’re at, understanding the risks, but also the benefits of having this topical therapy is really important for the patient for them to start taking the medication. I know from the pharmacy perspective, we see way too often returning to stock if somebody doesn’t pick up the medication, and sometimes the providers send out the prescription and don’t know that the patient never filled it. So really, overcoming that barrier of adherence is really important for these patients to make sure they’re taking the right dose at the right time for the right duration from the pharmacy perspective is really important.

Transcript edited for clarity.