Considerations for topical ruxolitinib with deference to positive clinical trial results in atopic dermatitis.
Lawrence Eichenfield, MD: Why don’t we move on to discussing some of the details of the topical program with topical ruxolitinib? There were 2 very large phase 3 trials that compared topical ruxolitinib with vehicle. Leon, we’re going to task you with telling us about the study design population outcomes.
Leon Kircik, MD: I’m still very excited about ruxolitinib, because it’s a topical drug. As dermatologists, topical treatment is the core of our treatment. As you know, it was a pediatric population as well as 12 and above. They had 2 randomized double-blinded studies parallel. I participated in those studies. I had 44 subjects in this study, and we also had part of the long term. The first part was 8 weeks of treatment, double-blinded, randomized vehicle control, and then everybody got into the open label for another 44 weeks for safety. We also looked at efficacy. The major inclusion criteria was that it had to be mild or moderate on the Investigator Global Assessment [IGA], which is 2 or 3. They had to have up to 20% body surface area. Of course, we had the washout period, which is standard for topicals for 2 weeks and orals for 4 weeks, and biologics were 5 times the half-life.
The bottom line we had about Investigator Global Assessment improvement, the coprimary end point, was clear. It was almost clear with a 2-grade improvement on the IGA. It was 53% on the higher dose. As Raj [Chovatiya] mentioned, there were 2 doses: 1.5% and 0.75%. I’m going to give you the results on the 1.5%. That was 53%, which is really impressive. We don’t want to compare studies because of different populations, but we saw 33% to 36% IGA with another study that was on patients who were moderate to severe. This is mild to moderate, but it’s still impressive. EASI [Eczema Area and Severity Index]–75 improvement was about 62%.
The itch was also measured. We looked at the percentage of the patients who had 4 points or more improvement on the itch scale on the NRS [Numerical Rating Scale], and that was 52%. More than half the people had improvement of 4 points or more. When you look at the population, 75% had moderate disease, which means a big chunk of patient population was moderate. Only 25% had mild disease. Mean body surface area was 10%, which is a point because you don’t want to use a topical on somebody who has more than 10% body surface area.
It had a very good racial distribution. Twenty-five percent of the patient population was African American, which is important in atopic dermatitis. We see a lot of African American patients. The drug worked equally well for everyone, regardless of age or racial distribution. It’s a very promising topical agent that I’m really excited about. Hopefully we’ll get it through the agency.
Lawrence Eichenfield, MD: From a safety and tolerance standpoint, is there anything you want to highlight?
Leon Kircik, MD: That’s a great question. There was no difference between the vehicle and active arm when you look at the adverse events. There were no tolerability issues. We didn’t see any of the issues that you see with the oral JAKs, and that’s a big concern. I don’t know what’s going to happen with the label. That’s the million-dollar question. Are they going to get the label with the oral JAKs or not? We don’t know. It’s up to the agency. But at least we didn’t see any of the adverse events that we see with the oral JAKs, and there were no local tolerability issues. Remember, we have 44 weeks of extended safety data.
Lawrence Eichenfield, MD: That’s 1 of the big questions we have. In this clinical study, they went up to 20% body surface area, and the adverse-effect profile read like topicals and not like systemic. There wasn’t evidence of systemic response. When we get to the oral JAKs, we’ll see the list of things that have been labeled for them that have been seen in clinical trials. That’s distinctive with our topicals. And also the tolerance. We’re not looking at datasets in a talk like this, but when we look at those data sets and drill down, the stinging and burning was higher in the vehicle arm than in the ruxolitinib arm. That makes me think it’s just the disease that’s causing the stinging and burning. We’ll see how that pans out in clinical practice because that will be something that would be really cool.
Leon Kircik, MD: That’s a rare occasion when you have a stinging and burning higher on the vehicle than the active arm. That speaks to the potency and the power of the anti-inflammatory effect of the active.
Lawrence Eichenfield, MD: Thank you for watching this HCPLive® Peer Exchange. If you enjoyed the content, please subscribe to the e-newsletters to receive upcoming Peer Exchanges and other great content in your in-box. Thank you.
Transcript edited for clarity.