番茄社区

Abrocitinib, a once-daily oral Janus kinase 1 (JAK1) inhibitor, showed long-term efficacy at doses of 100 mg or 200 mg in patients with moderate-to-severe atopic dermatitis, according to a recent study presented at the American Academy of Dermatology (AAD) virtual meeting.

In this exclusive 番茄社区 video, study author , president of Oregon Medical Research Center in Portland, discusses the results and implications of the JADE REGIMEN trial.

Following is a transcript of his remarks:

I presented results at the AAD meeting on a study called JADE REGIMEN, which was another study for moderate-to-severe atopic dermatitis patients. The design of this study is actually unique. There are no other study designs in the moderate-to-severe atopic dermatitis space that has these particular design elements. And importantly, the study was designed to look at what happens when you start off with a high-dose drug and you have a response, and then you have to decide what to do with a dose of that drug -- either to continue the same dose, to lower it, or whether to take the patient off.

So, first of all, the drug: in this case, the drug we studied was called abrocitinib. Abrocitinib is a JAK1 inhibitor. It's an oral blocker of JAK1, which is involved in pro-inflammatory pathways, in particular pathways involved in atopic dermatitis pathogenesis. And this drug had previously been shown to be effective in moderate-to-severe atopic dermatitis patients in pivotal phase III trials. And the doses that were studied previously were 100 mg a day and 200 mg a day.

So going back to the design of JADE REGIMEN -- in this trial, we gave all patients 200 mg a day of drug for 12 weeks. So essentially the high dose, the most effective dose for 12 weeks. And then we asked the question, did they respond or not? And about 65% of patients achieved an IGA [Investigator Global Assessment score] of 0/1 and EASI [Eczema Area and Severity Index] 75 response, which we labeled as a responder.

The other 35% of the patients actually were dropped from the study at that point and were not continued on because it was not the purpose to look at those patients anymore. Again, the purpose is to take responders and then, with maintenance therapy, check different things, different doses, to see how well they do with maintenance over time. So a third of the patients that were responders stayed on 200 mg, a third went to 100 mg (half the dose), and a third were put to placebo, and then the patients were followed from week 12 to week 52, so 40 weeks of follow-up on those three different maintenance doses to see what happens, to see if they flared.

So the interesting result is that -- first I'd like to talk about the two extremes of the data. So the extreme patients that were really challenging were the 200 mg patients who stayed on 200 mg, but 19% of them had atopic dermatitis flares, even though they continued on the high dose. So I call that the really tough population, the more severe patients, despite staying on the high dose, they had flare. And it was about 19%.

On the other end of the spectrum, really interesting, really fascinating, was what I call the super responders. And those are the people that were on 200 mg, they responded, and we put them to placebo -- took off drug -- and 19% of them did not flare. So 81% of patients, they flared, they needed drug and the disease came back pretty quickly. The majority of patients within 1 month of stopping this pill, they had disease coming back. But that curious population, kind of the extreme, some patients did not require continual drug -- again, 19% going to placebo.

And then if we look at the intermediate group, the ones who are on 100 mg, actually the majority of them did not flare. It was about 56% [who] did well. So 81% did well on 200 mg, 56% did well on 100 mg, 19% did well on placebo.

So the bottom line for the efficacy for preventing flares is, yes, the 200 mg dose is the best, 100 mg is the next best. And then placebo is the worst. But on an individual level, and if you're in private practice and you're using this drug and you treat [with] high dose for 3 months, you're going to have options. And this study gives practitioners the data they need to understand that not every patient is going to need continued high dose.

The other important piece that I haven't mentioned yet is safety. And with JAK inhibitors, we do see a number of possible safety issues, and we did see that in the study. Common things were acne, elevation of CPK [creatine phosphokinase], [and] drops in platelets that weren't dramatic, but some drop in platelet counts. So these are things that we see with JAK inhibitors and we saw them more commonly with 200 mg than we did with 100 mg. So another caveat is if you are concerned about safety or seeing safety issues with the higher dose, you would be expected to see fewer safety concerns at the lower dose, which is what we saw in the study.

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