Expert Perspectives in the Management of Pediatric Atopic Dermatitis - Episode 12

Efficacy and Safety of Ruxolitinib for Atopic Dermatitis Treatment

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Brittany G. Craiglow, MD, and Peter A. Lio, MD, provide insight into the efficacy and safety of currently available JAK inhibitors for the treatment of pediatric atopic dermatitis.

Raj Chovatiya, MD, PhD: With that being said, maybe we could talk about efficacy and safety when it comes to some of these treatments. In particular, the available JAK [Janus kinase] inhibitors, which I think are one of the bigger treatment revolutions we’ve seen. Peter, you can touch a little bit on topical ruxolitinib and talk about, in general terms, the phase 3 trials—what we saw and what’s this looking like in the real world.

Peter A. Lio, MD: Very interesting story, because we had used some topical JAK inhibitors off-label before, having them compounded. I know probably all of us have used them from time to time. A really important class of medicines, and when this one came out it was the first formulated topical JAK. It was approved back in September of last year. I think it’s been pretty impressive overall, very well tolerated, extremely reliable in general, most of my patients really respond well. It has a very good side effect and safety profile.

The biggest issue with it is that it comes with the prescribing information that looks an awful lot like, and frankly is almost identical to, the oral JAK inhibitors. We have discussion of malignancy, infection, major adverse cardiovascular events, and thrombosis. So patients look at this and say, oh my goodness what are you giving me? This is a cream. But I will point out that recently there was a maximal use study in adolescents where they had them using quite a bit over a longer period of time. They were able to show, pretty decisively, that even when you’re kind of overusing and abusing it, you can’t even get to about half the blood levels of medication that would potentially cause hematologic abnormalities. That doesn’t mean that it’s totally safe. I don’t mean to say that, but I do think that the risks are relatively low, especially when they’re used per the prescribing guidelines. The guidelines specifically point out it’s for use on less than 20% body surface area [BSA] and essentially noncontinuous use. In the way it was said, it was about 8 weeks at a time. I think if we follow these guidelines the safety will be quite favorable. I would be quite shocked to see major issues. Although it’s not impossible, and I don’t mean to minimize those risks, but that’s how I tell it to my patients. We’re going to be very cautious. We’re going to be conservative. And in that context with these smaller body surface areas and noncontinuous use, I’ve been very pleased.

One of the nice things about having a small molecule like this is that I think it penetrates extremely well. For thick, lichenified atopic dermatitis for hands and feet, it’s been quite impressive. The only other issue I’ll point out is that, unfortunately, the formulation contains propylene glycol. So some patients who are allergic to that, or if they have a known sensitivity to that, that can be a deal breaker for this particular formulation.

Raj Chovatiya, MD, PhD:I think you highlighted some of the big points I like to take away. When thinking about the phase 3 TRuE-AD1 and AD2 trials, I like to tell my patients that in 8 weeks of time with people using this, the majority of them had significant improvement in itch, what will be defined as clinically meaningful. A majority of them had clinically meaningful improvement in their lesions as well. There’s a variety of other secondary outcomes that show improvement that we think about from the more patient-reported standpoint.

To your point as well, I think that’s important that we do touch on the fact that there is this shared box warning language across topicals, across orals, when it comes to JAK inhibitors. We can take a sidestep into a little bit of that history lesson. A lot of this is based in many ways on the long-term, phase 4, 10-year oral surveillance project looking at tofacitinib, which is the JAK inhibitor that is mentioned in these labels. In patients who were treated who had rheumatoid arthritis, were over the age of 50, and had one cardiovascular risk factor. A lot of these things that we’re seeing at slightly higher rates compared to conventional therapy with TNF-α blockers; malignancy, VTEs [venous thromboembolisms], various lab abnormalities, infection, a lot of that comes from there. I think that with any of these medications, and you put it very nicely, you really want to be forward. Saying: “Hey, you’re going to get this medication that has this big patch there with all these things. Let’s talk about what that means, and let’s connect it to what was actually seen in the studies with the medication itself.” I think it’s paramount for all of us as dermatologists to be familiar with the data so you can come up with a very nice 1- to 2-minute discussion about high-level concepts on why this looks like this and why I’m worried or not worried in any regard. Any other thoughts on topical ruxolitinib that you want to convey to us, Britt?

Brittany G. Craiglow, MD: Yes. I agree with Peter. It’s nice to have another tool in our toolbox, and there are going to be patients for whom this is enough. Thinking about hand dermatitis or somebody who just has responded well to corticosteroids, but they can’t keep using them. It’s very nice. I think the impact on itch could be very fast. It tends to be well tolerated, which is a little bit different from some of our other nonsteroids. It’s a great option that we have for our 12 and up patients, and it’s a discussion. We’re used to that discussion with a lot of medicines, but especially tacrolimus. We’ve had that discussion in pediatric dermatology for a long time, so that’s familiar. Everything is about risk/benefit. Insurance companies are not going to pay for enough to be even close to maximal use, so that’s reassuring also.

Raj Chovatiya, MD, PhD: I will mention that for the purposes of how the label studies were done, typically 3% to 20% body surface area is what you’re thinking about for your patients. This practically makes sense since it’s a 60-gram tube. I think, much like Brit told us earlier, when people get 15-gram tubes to apply for 50% body surface area, that’s not going to work for a lot of your patients that fit this nice moderate range with that BSA. On average, in the studies, it was around 10%; it’s a great option. I’ll highlight 2 other things because we talked about some of those special sites. More than 40% of the folks in the phase 3 trials had facial, head, and neck involved as well. Given the limitations we have on conventional topical therapies in some of these regions, and we’re limited by potency, it’s another great choice in those regions. In terms that fast onset of itch, they saw it in 12 to 24 hours in terms of just looking at people’s numerical rating scores. It’s a great option across all of those.

Transcript Edited for Clarity