51成人动漫

51成人动漫 brought together three expert leaders for a virtual roundtable discussion on atopic dermatitis : Moderator Peter Lio, MD, of Northwestern University Feinberg School of Medicine in Chicago, is joined by Linda Stein Gold, MD, of the Henry Ford Health System in Detroit, and Alexandra Golant, MD, of the Icahn School of Medicine at Mount Sinai in New York City.

This third of four exclusive episodes explores safety monitoring of treatments for the condition. Click here to watch other videos from this roundtable series.

Following is a transcript of their discussion:

Lio: This brings us to our third question, which is really all about the pitfalls and the monitoring, and this is a perfect segue. So Dr. Golant, I've heard you talk very beautifully before on the black box warning on the JAK [Janus kinase] inhibitors, and I'm wondering if you could sort of summarize that for us here, what you might say to your patient when they say, "But doesn't this have a scary warning on it? What am I supposed to do with this?"

Golant: That's a great question, and I've heard you speak beautifully on it too, so I'd be curious to know how you deliver it. But I generally say that, "this entire class of medication," including the topical that's approved or topical JAK inhibitor that Linda mentioned, ruxolitinib [Opzelura], "has a boxed warning. This came from a higher risk patient population with a different JAK inhibitor that was thought to be more immunosuppressive."

"But in that study there was a higher rate of," and I go through the five kind of categories that are on that box warning, which are infection, mortality, cardiovascular events, clots, and malignancy. Then I say, "In the actual clinical trials of this medication I'm talking to you about in an atopic dermatitis population, what seemed to be a true signal, meaning thought to have correlation or cause-effect with the drug in a patient like you, really was limited to infections, particularly shingles and non-melanoma skin cancer."

That conversation lives best after having taken a really detailed history from your patients. So to Linda's point, are they 65 and up? Have they had a cardiovascular event or unprovoked clot? Are they a smoker? What else is going on in their life? Do they have an active malignancy? There are definitely buckets where you would think twice. I liked how Linda said that it's not a "never use," it's a "use your best judgment" and sometimes reach out to the other care teams to get their thoughts about it too. That's kind of how I approach it usually.

Lio: I couldn't agree more, and I love that idea that it's -- forced is strong, but it's true -- it's forced me to reach out to other care team members, which I think in dermatology we don't like to do as much. We tend to be kind of an island and we don't really love communicating as much as we should, but it has been great. I'll talk to the cardiologist, I'll talk to the oncologist. I'll say, "Listen, this is where we're at. These are our options." And I think for some patients the answer is going to be, no, we have to do something else, but for others it's going to be this still is the best choice, even though yes, there may be a higher risk profile, but we're going to do monitoring.

So Dr. Stein Gold, I'll turn it over to you. What, and understanding that the JAK inhibitor guidelines for monitoring, of course these are for the oral agents; there's no specific monitoring recommended for the topical ruxolitinib. But for the orals, it's a little bit vague; they give us kind of a leash. So I'm just curious personally, how do you usually go about it and what kinds of things are you thinking about when you're telling a patient how you're going to monitor?

Stein Gold: And I think that the fact that it's a little bit loose is a good thing, and because it might be different for each patient depending on their particular history, but I do get complete ... monitoring at baseline. You want to make sure their patients are not pregnant. You advise them it's not a good idea to get pregnant while taking an oral JAK inhibitor. Certainly the TB [tuberculosis] tests. But all baseline labs are done initially. And then you can look... and I've learned that all these young healthy people who come into your office are not young, healthy people. You pick up a lot of things on baseline labs that patients had no idea that they had. So I think that baseline monitoring is a great thing for patients in general.

And then often what I'll do, it depends really. With one of the oral medications, we can start to see changes within the first month, with the other one, it's within the first 3 months. So it really depends. But what I've found is, similar to what we did in the clinical trials -- and we've studied all of these agents in clinical trials so I'm fairly comfortable seeing these agents over the course of many years at this point -- but I'll tend to monitor heavier upfront, maybe at baseline, and then 3 months and then another 3 months, then see where things go. But in general, I'll probably, if somebody is on the medication and stable, I might check blood work twice a year.

Lio: That is so helpful, and it's just so great to have your wisdom and experience because I mean, obviously you treat a lot of serious dermatologic conditions and JAK inhibitors are a powerful member of this family. But maybe they're not even the most dangerous. I often think about how prednisone, cyclosporine, methotrexate, azathioprine, those are pretty big guns too, and arguably in some ways more dangerous than the JAKs. So we have this sort of apples to oranges. But I also don't want to totally blow over the biologics. I kind of said the biologics are an easier sell, but as you pointed out, they're not always an easy sell. Maybe easier but not easy.

So Dr. Golant, when you're talking to a patient about biologics, what kinds of safety and tolerability points do you bring up? And people still ask me this to this day -- I don't do any monitoring, but, do you or is there any monitoring you would do for a biologic patient?

Golant: I do not do any monitoring, and that was a departure for me. When they first were approved, I was doing monitoring just because I was so used to doing monitoring with our biologics for which we had biologics for psoriasis at that point, and then you end up finding things that don't preclude you from using the medication. So I said, no more. And that's per their label, right? I really do feel strongly we should be listening to the label. No immunosuppression, no box warning, no monitoring.

I think for both classes, for biologics and the JAK inhibitors, the patient's understanding of why you're talking to them about these medications lands best when you explain why we're talking to you about a systemic medication in general, because we understand atopic dermatitis is a systemic disease. And just like any other chronic condition -- high cholesterol, hypertension, you name it -- sometimes we need to intervene in a systemic way. That is usually my transition point to saying this is our menu. When I counsel about the biologics, usually from a risk or safety profile, I do mention no immunosuppression; this is not a steroid, probably like you've had before. Most of our biologics come with some elevated risk of not just conjunctivitis, but just overall ocular symptomatology: dry eye, itchy eye, irritated eye, red eye. So I talk through that. Sometimes I'll mention slight increase in herpes viral infections, which we're seen in many of the trials. Injection site reactions certainly.

But once you get to safety with the biologics, like you said, Peter, there's not that much to speak about. So that part usually goes pretty quickly once they have the buy-in of "Why are you talking to me about this medication in the first place?"

Lio: I love it. And since we have a couple of extra minutes, I'd love to just pick your brain. So you mentioned the eye issue, so conjunctivitis, keratitis, eye pruritus, dry eye, blepharitis, we see that kind of cluster. What about the face and neck dermatitis? Are you seeing that a lot?

Stein Gold: I don't see it that commonly, but I certainly do see it. And I have had patients that... and that's the reason why I have to take them off their biologic agent, and that's a time when I might consider going to an oral JAK. Because facial dermatitis can be really a problem. It's something that they think about every day. They walk into a room, their face is red, their eyes might be kind of red and swollen. It can be an issue. Again, I don't see it that commonly, but when I do see it, often it is an issue.

Golant: Yeah, I was just going to say I completely agree, and when I have a patient with predominant disease on the head and the neck, I will often say, especially for the biologics, "The trickiest areas to clear sometimes is this part of you [indicates face and neck]. So this is our starting point, but know there are other options if this doesn't become our final solution."

Lio: And then on the other side, with the JAKs, what are kind of the common things that come up? Dr. Stein Gold? Do you feel that the acne, and are there some other things that maybe are more tolerability things that might pop up for a patient?

Stein Gold: You think about the acne, the headache, a little bit of nausea early on, but for most of my patients, they really tolerate it quite well.

But I want to go back to one thing that you brought up. So I'm not sure what the incidence of the facial erythema is going to be with our newer biologic agents, with tralo [tralokinumab; Adbry] and with lebri [lebrikizumab]. I haven't seen it yet in my clinical trials with either of those or with lebri in real life. So that's something I think is still a little bit up in the air.

Lio: That is one of the most compelling things too because right, we've kind of lumped everything together, but they really are different drugs, and particularly the biologics. I mean, they're binding in slightly different areas, so dupilumab, tralo, and lebri, they're all the same pathway, but not fully, right? [Dupilumab] gets the IL-4 as well, so I'll be curious. It seems like the conjunctivitis signal is out there, and now it may be differential in terms of how common it is, but it seems like clinically it'll be comparable, but the face and neck maybe will be different, which would be wild.

For the JAKs, I feel like, again, they're pretty similar, but they're also different drugs. So yeah, I think that there may be some... I wish we had more biomarkers. I wish we had more insight into this so we could give more precision approach, but right now, I don't think it's crazy when someone says, "I failed this biologic, can I try another?" It's not necessarily ridiculous. They're not truly the same, especially if they've responded -- at least in my experience -- if they've responded to it in terms of their eczema but maybe had an adverse event, then I think it could definitely be worth switching to another biologic. If they didn't respond at all, then I feel like maybe it's time to switch categories and go to the JAK inhibitor. Would you guys agree with that?

Golant: I would. I would also add that I've seen the similar or same thing with the JAK inhibitors. I've seen a patient that might've had a partial not complete response to one, do very, very well on the other. So that surprised me too.

Stein Gold: Yeah, I think we're still learning so much, and I think the longer these medications are available, the more we'll truly understand. There have been some case reports of patients who were non-responders on one biologic or responded to the other one, but I think time will tell and we'll really get a better handle on how to approach these patients.

Lio: I love it.

Comment