Ruxolitinib in the treatment of atopic dermatitis

Casey Batlas, Ph.D.: I know you talk a lot about topical ruxolitinib, or Opzerra, which is a Janus kinase. [JAK] inhibitor.How does this mechanism of action actually differ from over-the-counter and other newer topical agents Euclisa? [crisaborole]?

Brian Keegan, M.D.: If I understand your question correctly, we’ve talked a little bit about steroids, but there are a few other non-steroidal anti-inflammatory drugs to consider, maybe three. We talked about tacrolimus, the name before it became pimecrolimus. [Elidel], Crisabrol. My understanding of these molecules is that they are believed to function through NFAT. [Nuclear Factor of Activated T Cells] Anti-inflammatory pathways are thought to operate by mechanisms similar to those of oral cyclosporine. And they can be effective. However, as mentioned above, its effectiveness may be limited. I don’t think most people consider them to be as effective as some of the stronger class 3, 2, 1 topical steroids.

One of the typical complications we encounter is a burning sensation, which can be difficult to sting. Therefore, we initially wanted to use these molecules in the desired areas to reduce skin thinning, i.e. facial use, axial use, groin use, where a person feels It is juxtaposed with a burning or stinging sensation. For office prescribers, the sales pitch of putting something on your eyelids or armpits can be difficult. When I got the sample, I applied it to my patients before they left the office, but sometimes they would cry before I got to the reception, so I knew I had to come up with a different plan. I was. Unfortunately, it was before that point. Therefore, there are many different molecules with potential advantages, but also challenges.

Casey Batlas, Ph.D.: yes. As you mentioned, you really want to avoid using topical corticosteroids on the face especially sensitive skin areas like the armpits, back of the knees and eyelids. I think it’s good that there are alternative mechanisms of action that don’t thin the skin and can provide patients with much-needed relief. I know I mentioned black box warnings for JAK inhibitors before. Ruxolitinib is a topical drug, so what are your thoughts on the black box warnings for topical drugs?

Dr. Michael Cameron, FAAD: No, I respectfully disagree with the box warnings on topical ruxolitinib, and frankly, I disagree with JAK inhibitors as a whole. I think the boxed warning is completely misunderstood.and a trial oral survey of tofacitinib [Xeljanz] In my opinion, this attempt was fundamentally designed to fail. They really accepted high risk people. Everyone was over 50.they had rheumatoid arthritis [RA]. They had at least one cardiovascular risk factor. All were taking a median dose of 17 mg methotrexate, 60% were taking chronic prednisone, and 40% were chronic smokers. So they took this really wealthy high-risk population and compared it to Humira. [adalimumab], which protects the heart in people with rheumatoid arthritis. So it’s a pretty tough comparison.

And with that said, I’m not sure many of my dermatologist colleagues realize how minimal the increased risk is even in that high-risk population. Looking at blood clots, for example, oral studies showed that he needed over 800 patients to harm. Now, compared to Humira, if he needs more than 800 patients for a single event, what harm does that number have to do to her 16-year-old with atopic dermatitis? Is not it. [AD] Nothing wrong with them? I would argue that it basically doesn’t exist. So, I have put over 100 of her on her JAK inhibitor and have not had a single safety issue with her. So, I love JAK inhibitors.

As for topical JAK inhibitors, including Opzelura, this is a highly absorbable molecule.When you see something like Tapinalov [Vtama], not absorbed. It’s a picogram. So the FDA said that if you were to apply this all over your body, you would essentially be taking ruxolitinib orally. So the FDA decided to go ahead with the in-box warning. But I have to say my experience with Opzelura was incredible. It’s a very good cream. There are no local tolerability issues. I’ve never heard of anyone saying it burns. And it is very effective. So if you think about it, it’s actually acting on all the cytokines that we know are important in Alzheimer’s hits IL [interleukin]-31, which is our itch cytokine. This affects thymic stromal lymphopoietin, IL-4, IL-13, and IL-22. To be honest, this is perfect for AD and I’ve had great experiences with it. Oh, yes.

Brian Keegan, M.D.: I think Dr. Cameron gave a great explanation of black box caveats. He will thank you for doing so. And I just pause for a moment and think one of the challenges is that the public doesn’t really understand what that means, but we still have to deal with it. , I would like to say. And perhaps, while I agree with Dr. Cameron, the warning may have been a little exaggerated. But if you really understand what it is, if there’s a very specific population you mentioned, maybe it’s not the best medicine for them. But like you said, your average 16-year-old coming into the office wouldn’t meet any of those criteria. And it doesn’t matter.

But the average family who goes home and looks up that information on the internet doesn’t have the educational background to make and understand that decision, and it just causes them a great deal of fear and anxiety. . And to be honest, patients are worried about what will happen if they use drugs, and we, who are looking after them, are also worried about what will happen if we don’t use drugs. How will their disease be adversely affected in the future? You have to balance each time you give a patient treatment, does this make it a more beneficial risk? Having said that, I think for 99% of the population, and probably a higher percentage, they will definitely benefit. If you have a super-subset of patients who don’t, I would avoid that 0.1% of patients and say that those patients may be at higher risk.

Dr. Michael Cameron, FAAD: Well said, Dr. Keegan. And I think it’s our job to translate what I said into the language of ordinary people and talk about it. So, in my case, counseling on JAK inhibitors is now only minutes and 5 sentences. And I’m not going to say to them, “I’m fine,” but the first word is, “This drug is a molecule called his JAK inhibitor.” And we have been treating rheumatoid arthritis for over 10 years. So I think we need to establish these legacies. And these are not experimental. If you walk into a room and say, “Yes, this is a JAK inhibitor,” it’s clear. There is a warning box and you can die. ” No one will accept that, right? But I doubt that’s a fair and balanced way to describe these treatments. So we see it as our job to package it up and deliver it in a fair and balanced way. These risks are possible, but I think they are pretty low for you.

Brian Keegan, M.D.: I think you expressed it beautifully too. And I think we both spend a lot of time educating our colleagues. And what we need first is we understand that prescribers need to be comfortable with their data. So with any new drug, it takes some time to dig deep and understand the pros and cons of that particular drug. What would my patients benefit from it? What would I need to talk to them about? These are all different kinds of questions that we all have to deal with.

And to follow up on your comment, say the patient likes kindergarteners and can smell fear. And when the prescriber said you did, you were half-hearted, I don’t know when you were given body language, I really don’t know about this. And the patient can sense it right away and tell you that you are uncomfortable with it. Therefore, step 1 involves making the prescriber feel good about what he or she is prescribing, and then projecting that onto the patient so that they understand, “No, it’s not.” I think the benefits for you far outweigh the risks. That’s why I think this is a great drug for you. ” I agree with you too. If you understand the data, you can understand it in five sentences. I’m not going to compare, but I’d probably do it in 2 or 3, but I’m probably not as successful as you.

Amy Brennan: I feel like that’s a big part of this situation. The burden of access is educating patients and explaining why they are taking the drug and getting them to go for it because they want to take it. We want them to start treatment and then continue treatment. A key element is that they take the first step in trying to fill the drug and then we can see if the drug is covered by insurance so we can work on the next steps. increase.

Casey Batlas, Ph.D.: Agree. I think there was definitely shared decision-making between providers and patients. As mentioned before, it is very important for patients to meet their situation and understand not only the risks but also the benefits of this topical therapy before they can start taking the medicine. From a pharmacy’s perspective, very often a drug goes back into stock if someone doesn’t receive it, and sometimes the healthcare provider who issued the prescription doesn’t even know the patient didn’t fill the prescription. . Therefore, from a pharmacy perspective, overcoming the adherence barrier is very important to ensure that these patients are taking the right amount at the right time for the right duration.

I edited the transcript for clarity.

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