Selection of JAK inhibitor therapy for atopic dermatitis

Bhavesh Shah, RPh, BCOP: Many JAK inhibitors are coming onto the market. Three of them are oral and one is topical, which is ruxolitinib. This is really interesting because from a topical point of view you are avoiding the systemic side effects that patients can have. Then based on the literature that I have seen with topical ruxolitinib there is a significant reduction in itching very quickly, within 12 hours of using it, then this is sustained for over 4 weeks. Some may even say that there is an equivalent benefit to an organic one. This reduction in itching within 12 hours from a topical point of view, which avoids systemic side effects, I think, is very appealing.

I think the cost of a biologic will always be much higher than that of a topical. Especially seeing some of the preliminary results and enjoying those benefits, [use of the topical agent] would certainly move higher in the criteria for use. Maybe even fail topically before the patient goes to see a biologic, or ask them to fail topically ruxolitinib before going to a biologic. Of course, we know that ruxolitinib cream will not treat patients with asthma, who need an agent like Dupixent, or allergic rhinitis or nasal polyps. I think some of these comorbidities can cause a patient to seek a biologic rather than ruxolitinib. topical cream. But I think there is definitely a larger pool of patients who would be eligible for therapy. Regarding the side effect profile of oral JAK inhibitors, this is not the case with atopic dermatitis, but recently we have seen a communication from the FDA indicating that agents such as baricitinib and upadacitinib and Xeljanz all carry this FDA warning for increased blood clots and other side effects, such as cardiovascular events. This has been observed in other indications such as rheumatoid arthritis [RA] but mainly carried over to indications like GI [gastrointestinal] also.

I think suppliers may be hesitant to choose a JAK inhibitor over a cream, especially given the recently released FDA warnings that have changed the label of these, especially with Xeljanz and baricitinib , that patients should fail biological therapy. as an anti-TNF [tumor necrosis factor] before they were considered for JAK inhibitors. Obviously, they didn’t say this applied to indications other than RA and IBD. [inflammatory bowel disease], where Xeljanz is used. I think having these kinds of warnings would definitely be a consideration.

But the other thing I have to mention is that we have also identified that JAK inhibitors provide benefit in patients with alopecia along with atopic dermatitis. It’s a huge impact on patients across various comorbidities. I think the patients would also prefer to have multiple benefits even if the supplier is going to get the cream first.

I should mention one more thing because COVID-19 is still here; he’s not gone. But baricitinib is approved via an EUA [emergency use authorization] for patients with [COVID-19–related] ARDS [acute respiratory distress syndrome] pneumonia. There is this other aspect that suppliers can think of. Say they have a patient who is highly immunocompromised and if they have been vaccinated but still are not sure how much antibody protection they can have, having a JAK inhibitor, which is approved by an EUA for ARDS pneumonia linked to COVID-19, if this patient develops COVID-19 and ends up having this overactive cytokine release syndrome, there may be a benefit for these patients. There are so many ways to get this to work out, but I think we would definitely prefer the cream over the oral agents, based on cost as well, primarily, and effectiveness.

Peter A. Lio, MD: Right now, because topical JAK inhibitor is so expensive, it is several orders of magnitude more expensive than the products we currently have on the market. I reserve this for patients who have really 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 serious patient, it is not a suitable thing to try. But for those patients who still need it, I’m really excited about it. There is no doubt that for some patients this could potentially mean the difference between having to take a systemic agent and not, if we can better control them. So it’s exciting.

For the oral ones, I think for my personal practice at this time, they will generally be reserved for severe patients. It’s not something that I think I’ll try unless they really need it. Ideally, they will have failed something like a first biologic for my practice, as I think biologics, in general, seem to have a more favorable balance between safety and efficacy, at least as written. Again, this is the hardest part because the black box warning sounds so harsh, even though the truth is not quite on that level, it makes our life a little harder when we let’s talk to a patient.

They’ll probably initially be for patients who have had failures, who have done these other things, but if they prove to be successful and with experience we might start to say, you know what, they’re easier to handle. use. It’s a pill; it is not a hit. And maybe, like I mentioned, we can use them in smaller bursts for patients, sometimes to be a real steroid-saving agent. I am excited about all of these options because we have so many unmet needs.

Transcription edited for clarity.

Martin E. Berry