Transcript
Michael Lewitt: Hi, I’m Michael Lewitt. I’m a dermatologist in Chicago. I’m a partner with the Illinois Dermatology Institute, and I lead and perform medical dermatology trials with DeNova Research. Thank you for having me.
What patient-reported outcomes can reveal in atopic dermatitis that traditional clinician-assessed measures miss are a number of things, so it’s multifold. Number one, PROs, or patient-reported outcomes, in atopic dermatitis really describe the patient experience with their disease. We have an opportunity as clinicians and providers to ascertain more information on certain things like itch, sleep, bleeding, et cetera. They also elicit information on how a patient likes or dislikes their chosen therapy.
For example, topically, was the medication elegant? Did it sting? Did it burn? How was it absorbed? Was it greasy? Did it smell bad? And then systemically, if something is an injectable medicine, did it hurt? Was the device easy or hard to comprehend, to teach, or to use on themselves or somebody else? How long did it take? Or, if it’s oral, was the pill too large? Was it easier to use something daily versus biweekly or monthly?
So those are just a number of examples of how PROs can really help ascertain more information in atopic dermatitis that clinician-assessed measures may miss.
I’ve absolutely encountered situations where a patient’s reported disease burden differed substantially from what I saw clinically, and I’ll tell you how I handled those situations. Usually, but not always, a patient’s patient-reported outcomes or experience are commensurate with achieving high levels of EASI score thresholds, like an EASI 75, 90, and, even harder to reach, an EASI 100.
But every once in a while, the patient experiences an adverse event, either safety- and/or intolerance-based, like an injection-site reaction versus nausea versus weight gain. Those are examples of intolerabilities. They’ll report a patient-reported outcome that’s not corresponding with their skin clarity. Also, very rarely, we’ll sometimes see when the skin clears but the pruritus is still present, and the patient’s PROs are still not equal to what we’re seeing on exam.
There are absolutely three important patient-reported outcomes that I find most important, in no particular order. If you were to ask me these three and give me them and ask me to rank them, I would say yes, yes, and yes. And those are itch, sleep disturbance, and pain.
I find those most important for the patient, and they honestly go hand in hand. If somebody’s itchy, they’re probably having trouble sleeping. If they’re in pain, they’re going to have trouble sleeping. But I do feel that a person who has suffered from something like atopic dermatitis or urticaria, for another example of an itchy condition, for a long period of time has a different baseline than maybe you or I would have if we had a mosquito bite, et cetera. So their baseline is different than the rest of us who don’t suffer from those itchy conditions.
I think that each disease state has a patient-reported outcome that would be most important. For example, itch and sleep for atopic dermatitis, perhaps pain for a disease state like psoriatic arthritis or hidradenitis suppurativa. Each one can be encompassing of the others as well.
But there are other functions that are really implicated in patient-reported outcomes that are a direct result of the aforementioned, things like intimacy, activity, and work productivity. So there are a lot of things that are a result of not having the ability to clear things, as we mentioned, like itch, sleep disturbance, and pain.
I find it very important that a drug like tapinarof has shown statistically significant positive patient-reported outcomes. For example, in the ADORING trials, tapinarof had a statistically significant itch reduction from vehicle as early as day 2.
So why is this important? Well, as I described in the last question, that early matters because itch is often the symptom that most immediately disrupts sleep, concentration, and daily life. And if you can turn off that faucet, the other aspects of the disease state have a better chance of healing, and patients have better-reported outcomes.
I think it’s really important for our audience to know, those who don’t do clinical trials, that the Peak Pruritus NRS score is an 11-point scale from 0, which is no itch, to 10, which is the worst itch imaginable in the last 24 hours. A higher score usually indicates more severe symptoms.
So when we look at that PP-NRS score in the eyes of the FDA, which is often a secondary endpoint, it looks at a greater than or equal to 4-point reduction in the average weekly score from baseline.
For example, we saw tapinarof at week 8 versus vehicle. And when you saw tapinarof versus vehicle, tapinarof achieved this about one and a half to two times more than its vehicle.
So hopefully that gives a bit of understanding for folks who don’t do clinical trials or don’t mark this in their electronic medical record. I always try to because it helps get drugs approved and really shows, as a clinician, how patients do better from their baseline to when I prescribe the therapy to when they come back for follow-ups. It also helps me elicit whether or not I need to add things or change things.
