Oral JAK Inhibitors

In this video, April Armstrong, MD, MPH, discusses the latest evidence for oral Janus kinase inhibitors, a growing and exciting therapeutic avenue for atopic dermatitis. Dr Armstrong is professor of dermatology and associate dean of clinical research at Keck School of Medicine of University of Southern California in Los Angeles.

Transcript
Dr Armstrong:  I'm going to continue to talk a little bit about JAK inhibitors. JAK inhibitors, for atopic dermatitis, is a hot area. What we know in terms of JAK inhibitors as a class, for example, that are being studied for the AD, is that all of them can improve itch pretty rapidly. The response can be within days of starting JAK inhibitor.

What's also noted is that not all JAK inhibitors are the same. The efficacy, the tolerability, and also the safety profile depend on not only the molecule itself but also on its dose. It's important to know that there are some safety and tolerability outcomes that we may want to think about when using the JAK inhibitors. Again, this will vary depending on the specific JAK inhibitor that we're talking about. One thing that seems to be a bit more common, perhaps related to this mechanism of action, is herpes zoster and also HSV infections. They seem to occur at greater proportions in patients on the JAK inhibitors vs those that are on placebo, but most of them can be treated in the medication typically the JAK inhibitor can be continued.

I'm going to talk a little bit about some of the specifics regarding the different types of JAK inhibitors.

The first one is baricitinib. Baricitinib is the lowest dose JAK inhibitor. What's known is that, even though when we look at the overall efficacy is more modest for baricitinib, it seems to have very good efficacy when we look at patients who have more moderate disease. Those are patients with less than 50% of BSA. When we think about side effect profile for baricitinib, it's probably the best tolerated JAK inhibitor among the three that we're talking about today. There's low rates of nausea, vomiting, or acne with baricitinib. Again, as with all three JAK inhibitors, we see increased rates of HSV—less than 4%—and zoster was also seen but at low frequency—less than 1%.

One thing is that serious infections are not increased with baricitinib. Also, malignancy rates were lower than that of placebo and also remain low over time. This is really important. There were also no venous thrombosis at 2 mg dose that were observed. In terms of the VTE signal at the 2 mg dose, we won't see any at this time. At baseline, we want to check labs such as CBC, CMP, cholesterol, tuberculosis status, viral hepatitis, and also at 12 weeks at a minimum.

Now, we'll go to abrocitinib, another JAK inhibitor. Now, abrocitinib has two doses. What has been shown is that the 100-mg dose, the lower dose, have efficacy that is similar to dupilumab, and the 200-mg dose have efficacy that's possibly better than dupilumab. Abrocitinib has high efficacy.

There is those related nausea that has been noted in the studies up to about 15%, but they tend to be transient. Also, zoster and HSV have been observed in patients that in most cases, those have resolved with treatment. It's noted that there's some rare, 5% percent or less, transient platelet reduction at week 4 in some of the trials.

The venous thrombosis events are quite rare at .3 per 100 patient years, which is similar to the background atopic dermatitis VTE rates regardless of therapy. I just wanted to mention that aspect of it. Again, laboratory monitoring is likely needed.

Then the last JAK inhibitor that I want to mention is upadacitinib. In terms of upadacitinib, it's probably the highest efficacy of JAK inhibitor at the highest dose. It is important to note that for upadacitinib at its highest dose, which is 30 mg, studies have shown that is superior to dupilumab. When we think about your upadacitinib, we know that it's known for its very high efficacy.

What about the safety profile? Overall, it's well tolerated. Acne is something that we see that seems to be a bit unique have a side effect profile for upadacitinib and that can occur up to 17% at the higher dose of 30 mg. Again, herpes zoster is seen with upadacitinib as is seen with other JAK inhibitors. With regards to serious infections, it occurs in less than 1% of the treated population. Neutropenia can occur in up to 5% of patients, as well as lymphopenia. Therefore, it's important to make sure that we do the baseline laboratory workup, as well as ongoing monitoring with upadacitinib.