James Q Del Rosso, DO, Raj Chovatiya, MD, PhD, Lisa Swanson, MD, discuss the week 8 change results of ruxolitinib cream from the TRuE-AD1 and TRuE AD2 phase 3 trial.
James Q. Del Rosso, DO: The mean daily itch score is the baseline, based on the Worst Itch Numeric Rating Scale. We’re going to be focusing on 1.5% ruxolitinib [Opzelura] cream because that’s the percentage that is FDA approved and is in your hands in the clinic. The 0.75% ruxolitinib cream had very good activity, but the 1.5% ruxolitinib cream did better overall. It didn’t have any safety signals that would prompt the FDA to say that we need to go to the lower dose. That’s why we’re focusing on the 1.5% ruxolitinib cream. They had a 5.1 mean score at baseline. By day 56, in the active group that had been applying the 1.5% ruxolitinib cream, the mean itch score went down to 1.8. In the vehicle cream group, it did go down. You have some value from applying a vehicle cream that’s not irritating and provides some soothing benefit to the disease—you’re not applying nothing to the skin—but it brought it down substantially less than the active cream did. The vehicle cream was 3.5, whereas the active cream was 1.8. That was on day 56.
At week 8, the change from baseline in the results looking at itch reduction was 80% vs 48%. Patients who were utilizing ruxolitinib cream actively had an 80% change from baseline compared with slightly less than 50% with the vehicle cream. Keep in mind, we’re not discounting the improvement of eczematous dermatitis. That obviously improved, but we’re focusing on the effect on itching. Because let’s say you’re 2 weeks into it, and these patients are miserable at baseline and have significant itching. Now you’re 2 weeks into it. The eczematous dermatitis—the visible appearance of the eczema—is dramatically better, but they’re still having significant itching. They’re not happy. They don’t want to keep eczema around, but if they had to make a choice, the vast majority of patients are going to want to get rid of the itching. If you had to get rid of 1 first, get rid of the itching. The skin is going to take longer because it has to change and turn over. With itch, you can have a significant effect early, depending on the mechanism of action, if you’re affecting the signals affecting the sensory nerves that cause itching.
Over half the patients who used the ruxolitinib cream achieved itch reduction, which was at least a 2-point reduction from baseline in their itch by week 8. In the individuals who were applying 1.5% ruxolitinib cream, at week 2, 54.6% had at least a 2-point reduction in their itch. The criteria typically used in the study as the end point is a 4-point reduction in itch. That’s the bar the FDA sets. A good amount of data support that a 2-point reduction in itch is clinically meaningful to patients. It’s very noticeable. That’s why this was looked at in this particular analysis. As you continue using the application, you’re now up to two-thirds of the patients at week 4 and week 8 having at least a 2-point reduction in itch. The vehicle cream was substantially lower. It’s not 0. You’re applying a cream, but it was in the 20% range and maybe about 30% if you rounded off by week 8, but it’s substantially lower with the vehicle cream. The ruxolitinib is inducing activity against itching. That’s profound.
Raj Chovatiya, MD, PhD: The top-line results from the itch data that I want to highlight are that from baseline to week 8 of treatment, on average, about 3.1 to 3.3 points on that 1 to 10 scale is where patients treated with ruxolitinib dropped. This is in comparison with about 1.5 points for the vehicle cream. There’s an immediate statistical difference and almost double that actual amount.
If we’re talking about pure itch relief of any kind, 80% of patients treated with ruxolitinib have had some. This is what we were talking about when we were referring to the Swanson happiness index— any improvement matters. Maybe we can look at the numbers and work through the data.
Lisa Swanson, MD: The remarkable thing about topical JAK inhibitors, like ruxolitinib, is the fast onset of action, particularly when it comes to itch. This was observed in the studies TRuE AD1 and TRuE AD2. There was remarkably fast improvement in itch for our patients. That’s very meaningful.
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