JAK Inhibitor Treatment Selection for Atopic Dermatitis


Drs Shah and Lio explore where topical ruxolitinib fits into therapeutic sequencing in atopic dermatitis, compared with oral JAK inhibitors.

Bhavesh Shah, RPh, BCOP: Numerous JAK inhibitors are coming to the market. Three of them are oral and then one is topical, which is ruxolitinib, It’s really interesting because from a topical perspective, you avoid the systemic adverse effects that patients may have. Then based on the literature that I’ve seen with ruxolitinib topical, there is a significant reduction in itching very quickly, within 12 hours of using it, and then that’s sustained for over 4 weeks. Some may even say that there’s a benefit that’s equivalent to a biological. That reduction in itch that is within 12 hours from a topical perspective, which avoids the systemic adverse effects, I think, is very appealing.

I do think that the cost of a biologic is going to be way higher always compared to the cost of a topical. Especially seeing some of the preliminary results, and having those benefits, [use of the topical agent] would definitely move higher in the utilization criteria. Maybe even failing the topical before the patient goes to a biologic, or requiring them to fail the ruxolitinib topical before they go to a biologic. Of course, we know that ruxolitinib cream is not going to treat those patients with asthma, who require an agent like Dupixent, or allergic rhinitis, or nasal polyps.I think having some of those comorbidities may push a patient to get a biologic over ruxolitinib topical cream. But I think there’s definitely a bigger pool of patients who would qualify for the therapy. Talking about the adverse effect profile of oral JAK inhibitors, this is not the case with atopic dermatitis, but recently we’ve seen a communication from the FDA that agents such as baricitinib and upadacitinib and Xeljanz all carry this warning from the FDA for an increase in blood clots and other adverse effects, such as cardiovascular events. This was seen in other indications like rheumatoid arthritis [RA] but essentially carried over to indications like GI [gastrointestinal] as well.

I think there may be hesitation from providers to reach for a JAK inhibitor over a cream, especially because of the FDA warnings that have come out recently, which changed the label of these, specifically with Xeljanz and baricitinib, that patients should fail a biologic therapy such as an anti-TNF [tumor necrosis factor] before they should be considered for JAK inhibitors. Obviously, they haven’t said that it applies to other indications besides RA and IBD [inflammatory bowel disease], where Xeljanz is used. I think that having those types of warnings would definitely be a consideration.

But the other thing I should mention is that we also have identified that the JAK inhibitors provide benefit in patients with alopecia concurrently with atopic dermatitis. That’s a huge impact on patients across various comorbidities. I think patients would also prefer having multiple benefits even though the provider is going to be reaching for the cream first.

I should mention one other thing as COVID-19 is still around; it hasn’t gone away. But baricitinib is approved through an EUA [emergency use authorization] for patients with [COVID-19–related] ARDS [acute respiratory distress syndrome] pneumonia. There is this other aspect that providers may be thinking about. Say they have a patient who is highly immunosuppressed and if they’ve been vaccinated but are still not sure about the amount of antibody protection they may have, having a JAK inhibitor, which is approved through an EUA for COVID-19–related ARDS pneumonia, if this patient develops COVID-19 and ends up having that overactive cytokine release syndrome, there may be a benefit for these patients. There are so many ways to spin this, but I think we would definitely prefer the cream over the oral agents, based on the cost, too, primarily, and the efficacy.

Peter A. Lio, MD: Right now, because the topical JAK inhibitor is so expensive, it is orders of magnitude more expensive than the things we have on the market right now. I’m reserving it for those patients really who have in earnest tried and failed at least topical steroids, probably one of the calcineurin inhibitors, and potentially, it’s not always appropriate, but crisaborole. The thing is crisaborole, as we said, it has its own niche, and for many, especially a severe patient, it’s not an appropriate thing to try. But for those patients who still need it, I’m really excited about it. There’s no doubt that for some of the patients, this could potentially mean the difference between having to go on a systemic agent and not, if we can get them under better control. So that’s exciting.

For the oral ones, I think for my personal practice right now, they’re going to generally be reserved for severe patients. They’re not something I think I will dabble in unless they really need it. Ideally, they will have failed something like a biologic first for my practice, because I feel that the biologics, in general, seem to have a more favorable safety and efficacy balance, at least the way it’s written. Again, that’s the hard part because the black box warning is so severe sounding, even if the truth is not quite to that level, it does make our life a little bit harder with talking to a patient.

They are probably going to be initially for patients who’ve had failures, who’ve done these other things, but if they prove themselves and as we get some experience, maybe we’ll start to say, you know what, they’re easier to use. It’s a pill; it’s not a shot. And maybe as I alluded to, we will be able to use them in smaller bursts for patients sometimes to be a true steroid-sparing agent. I’m excited about all of these options because we just have so many unmet needs.

Transcript edited for clarity.

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