Announcer:
You’re listening to DermConsult on ReachMD. On this episode, we’ll discuss the LEVEL UP trial that compares upadacitinib to dupilumab as atopic dermatitis treatments with Dr. Christopher Bunick, who recently spoke about the LEVEL UP trial at the 2024 Fall Clinical Dermatology Conference. Dr. Bunick is an Associate Professor of Dermatology at Yale University School of Medicine, and he specializes in general medical dermatology and dermatologic surgery. Let’s hear from Dr. Bunick now.
Dr. Bunick:
LEVEL UP is a very important trial for atopic dermatitis and dermatology as a whole. One of the reasons that LEVEL UP is so impactful is because it incorporates for the first time ever in an atopic dermatitis trial a composite endpoint where patients, as a primary endpoint, were not just trying to have EASI 90 or clear skin. It was EASI 90 and itch 0 or 1 on a 10-point numerical rating scale.
So a task force known as AHEAD, Aiming High in Eczema and Atopic Dermatitis, made several recommendations that came out in the last year or so talking about this idea of optimizing treatment targets in atopic dermatitis, which involves obtaining a clinician-reported outcome, such as skin clearance, and combining it with a patient-reported outcome, such as itch.
LEVEL UP is looking at patients head to head on upadacitinib versus dupilumab per label. So this is the first study that actually is using upadacitinib at the 15 mg dose first and then has the ability to go up to the 30 mg dose.
So Period 1 of LEVEL UP is from week 0 to week 16; the primary endpoint at week 16 was this composite EASI 90 and itch 0 or 1. And just to summarize the data from Period 1, upadacitinib rounded up to 20 percent of patients achieved this composite endpoint by week 16 compared to only 8.9 or 9 percent of dupilumab patients.
What I was presenting for the first time at the fall clinical meeting was Period 2—the week 16 to week 32 time period. This particular time period was very different. So first, patients that were on dupilumab in the Period 1, week 0 to week 16, that did not achieve EASI 75, they were switched to upadacitinib 15 mg. And then the question was asked over the next 16 weeks: those patients that did not achieve EASI 75 on dupilumab in the first 16 weeks, how did they fare switching to upadacitinib with no washout period?
All of the patients that were on dupilumab that did not achieve EASI 75—within four weeks of switching to upadacitinib 15 mg, 67 percent of the patients now achieved EASI 75. If you go out for the full 16 weeks and you look at week 32 data, 80 percent of patients that could not achieve EASI 75 on dupilumab are achieving EASI 75 with upadacitinib switching to the 15 mg daily dose. And so what we’re seeing is that dermatologists have to be aware that if a patient isn’t achieving good skin clearance or good itch relief on dupilumab, they really should be switching therapy within three to six months to something else that could do better.
I think there’s two key ways this changes how we practice. Clinicians want to know when to switch to the higher dose. So this trial gives us a clue as to when to do this. At week 4, if your patient isn’t hitting EASI 50 or not having a good enough itch response, then you can up the dose to the 30 mg of upadacitinib. And at week 8, four weeks later, if someone’s not achieving what you think is the right skin or itch clearance, then you increase them again or you increase them from 15 to 30 if they’re on the 15. So these are really important real-world scenarios that inform us when to increase the dose of the oral JAK inhibitor.
To me, the single biggest take-home point from Period 2 of LEVEL UP is that we as providers cannot be complacent to keep our patients on dupilumab just because we’re used to dupilumab or we’re comfortable with dupilumab. The truth is that data shows that there’s going to be a significant number of patients that are not hitting optimal treatment targets with dupilumab. This is what’s really important—having these benchmarks now helps us in the real clinical setting evaluate our dupilumab patients better. Is this patient hitting minimal disease activity or optimal treatment targets? If they are, keep them on their therapy, keep them on dupilumab. But there’s going to be patients that aren’t hitting that optimal treatment target, and those are the patients where you have to recognize their quality of life is not doing as well as it should because their optimal treatment targets are not being hit for atopic dermatitis.
The most important thing for my colleagues to recognize is that the standards of care of treatment in atopic dermatitis are being elevated. It is important to consider the entire patient, both the skin clearance and the patient-reported outcomes. Itch, sleep, quality of life—all of that matters in the big scheme. That’s what we’re learning. We really should be focusing on elevating the standard of care of our atopic dermatitis patients with the knowledge that we’ve learned from the AHEAD recommendations, the concept of minimal disease activity, and the data from the LEVEL UP Period 1 and Period 2 trial.
Announcer:
That was Dr. Christopher Bunick talking about the LEVEL UP trial. To access this and other episodes in our series, visit DermConsult on ReachMD.com, where you can Be Part of the Knowledge. Thanks for listening!
