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Oral JAK Inhibitors for Atopic Dermatitis


Experts discuss newly approved oral JAK inhibitors for the treatment of atopic dermatitis.

James Q. Del Rosso, DO: We have 2 new oral Janus kinase [JAK] inhibitors. Oral Janus kinase inhibitors are being looked at for a variety of different areas, not only atopic dermatitis. Atopic dermatitis is where they’re coming into dermatology. We have many of them approved for other disease states that our colleagues treat, but abrocitinib [Cibinqo] has not been available for other disease states. It’s new on the market, first for atopic dermatitis, which is primarily a Janus kinase 1 inhibitor. And then upadacitinib [Rinvoq], which is available for the treatment of other disease states but is now also FDA [Food and Drug Administration] approved for atopic dermatitis.

There are some differences in the labels. These are for patients with moderate to severe disease. It’s very similar to the patients that were put into the dupilumab [Dupixent] studies and also now the tralokinumab [Adtralza] studies, that being approved in IL-13 [interleukin 13] monoclonal antibody. And we’re familiar with dupilumab inhibiting IL-4 [interleukin 4] and IL-13 as a monoclonal antibody. Those are not Janus kinase inhibitors. But the type of patients that went into this study were patients that are not responding to prescription topical therapies or were no longer candidates for other means of getting their disease under control. They had EASI [Eczema Area and Severity Index] scores of at least 16 and body surface areas of at least 10%. The majority of them were at least about 40% to 50%, or even higher, body surface areas, with extensive eczematous dermatitis.

Some of the studies would allow topical corticosteroids. The abrocitinib study did not, which is important. They did not allow topical corticosteroids in their pivotal trial that we’ll be discussing. The upadacitinib study did, so their label does have “with or without topical corticosteroids.” But abrocitinib is approved for patients that are adults in the disease of manifestations that I mentioned: refractory disease and disease that is difficult to control with prior prescription topical treatments, with moderate to severe atopic dermatitis.

The recommendations for both abrocitinib and upadacitinib is to start out with the lower dose. In the case of abrocitinib, it’s 100 mg once a day, and then if the patient is deemed not to be responsive, you would step up to the 200 mg once a day. With the upadacitinib, it was approved in adults and adolescents. That’s 1 difference, but also it is recommended to start with 15 mg once a day, and if they’re not felt to be responsive, then you can go up to 30 mg once a day. The label recommends starting with the lower dose, but those lower doses are not as effective as the higher doses in their own trials, so they are considerably effective in all of the end points. What’s your sense on that, at least for those 2 drugs and some of the differences in the labels that I mentioned?

Neal Bhatia, MD: Our site was involved with both of the trials for both drugs, so we were very happy to see them get approved on January 14th. Again, 1 advantage probably that upadacitinib had was that it was already on the market for other rheumatological indications. Whereas, like you said, abrocitinib was a brand-new drug in that respect. I think 2 things come to mind when you think of dose ranging. You have to make sure that there’s adequate laboratory monitoring within the dose change if you are making that elevation in case CBC [complete blood count], lipids, [or] liver are of any issue in the first place.

The second comes back to if we are using enough adjuncts. To your point about approval with topical steroids, we want to have enough adjunctive treatment working from the top down while we’re still getting things under control orally. But, as an entire class, I think the advantage is speed. You see the speed of onset within 7 days. The NRS [numeric rating scale] data within 3 days is striking with all the class of drugs. Again, to get patients out of their own jail when they’ve been scratching and not sleeping is very significant.

The concern I have is that we’re going to focus a lot on severe patients and we’re going to forget about our moderate patients when it comes to this class of drugs or any systemic therapies, for example. Again, where we’re using prednisone tapers, or where we were using cyclosporine and methotrexate, I think we have real opportunity now with the speed of JAK inhibitors, and this includes both drugs, to again get a lot of that disease under control very quickly. The focus on safety is important, but the focus on speed of efficacy and speed of getting patients better has to be paramount to thinking about these 2 drugs as well as everything else. You mentioned about baricitinib [Olumiant]. I don’t know why exactly they were not on the same approval timeline, but I think the alopecia areata data that they have may be their focus. And I don’t want to speak out of turn, but I think that’s probably where we may see baricitinib soon.

James Q. Del Rosso, DO: Well, they definitely have emphasis there and I think we’re expecting that to come up pretty soon with baricitinib, and there were other Janus kinase inhibitors like ritlecitinib that is in development also. For alopecia areata and vitiligo, the responses are going to take longer typically than they will with atopic dermatitis, but those are very important areas. I do want to mention that with abrocitinib, it did also have in the label that if patients have moderate renal failure, start with an even lower dose of 50 mg once a day. The label also had some potential drug interactions with drugs that are metabolized by cytochrome 2C19 and even cytochrome 2C9. Those are some considerations, and a contraindication is that they allow low-dose aspirin, but for any other drugs that affect platelet function or platelet count within the first 3 months, it’s recommended not be used with abrocitinib. Our colleagues need to be aware of what is in the label, but both of these agents have very favorable efficacy results.

With the laboratory monitoring, there are a lot of questions about that. In general, the recommendation with these agents is that you get a baseline complete blood cell count, a chemical profile, QuantiFERON Gold to look at TB [tuberculosis], hepatitis B, hepatitis C at baseline, and, if they’re at risk, HIV testing. Then, at 4 weeks and then every 3 months, you repeat these, but also be sure you’re looking at lipids and CPK [creatine phosphokinase] levels. CPK levels may occasionally go up in some of these patients. It’s interesting that in the review by several other experts that was published a few years ago by Dr Peter Nash [Griffith University School of Medicine, Herston, Gold Coast, Australia], they didn’t recommend CPK levels as routine. But I believe these are considered now to be something worthwhile to look at.

Neal Bhatia, MD: The 1 thing I do caution everybody about is dose changing. Because, in the old days of tofacitinib [Xeljanz] and with other drugs of similar character, there were some incidences of lipid elevation as well as transaminase elevation. Again, this is probably more in patients who were at high risk and again, it was more involved when the dose was changed. Now we’re learning, like all the lab parameters you mentioned, that those came from clinical data that we learn from. I think to your point, following that recipe and sticking to it is going to be critical to keeping that success.

James Q. Del Rosso, DO: As you mentioned, when you’re changing doses, if the patient is stable, as I mentioned earlier, if they started on a lower dose and you’re going to increase to the higher dose, then you need to step up your monitoring as Neal mentioned.

Transcript edited for clarity.

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