touchDERMATOLOGY coverage from EADV 2024:
Twice-daily continuous application of ruxolitinib cream, a topical selective JAK1/JAK2 inhibitor, has been reported to be safe and effective in treating children with mild to moderate atopic dermatitis (AD) over an 8-week period in the TRuE-AD studies.1,2
In this interview, we talk with Dr Amy Paller from the Northwestern University Feinberg School of Medicine, Chicago, IL, USA who presented the 52-week results from the phase III TRuE-AD3 study (NCT04921969), investigating the long-term safety and efficacy of ruxolitinib cream, applied as needed, in individuals aged 2–11 years with mild to moderate AD. Our discussion focuses on the studies long term key findings and how this data could affect how we treat young patients with AD.
Q. Could you tell us about the design of the TRuE-AD3 study?
This was a trial in which for the first 8 weeks, children were randomized 2:2:1 to receive either 0.75% strength ruxolitinib cream, 1.5% strength ruxolitinib cream or placebo cream twice daily.
During the first 8 weeks, patients stayed on what they were originally assigned. Then at 8 weeks, the children who were initially randomized to ruxolitinib cream remained on their regimen and those who had been receiving placebo were re-randomized 1:1 to either 0.75% ruxolitinib cream or 1.5% ruxolitinib cream for an additional 44 weeks of as-needed treatment.
Overall, in this long-term extension study, the mean age of the children (n=282) was 7 years old and about half of the participants were female (52.8%). The study was for mild to moderate atopic dermatitis – those with an Investigator’s Global Assessment (IGA) score of 2 and 3 – but about 77% of those included in the study were moderate in severity with a mean peak itch Numerical Rating Scale (NRS) score of almost 7.
It’s important to note that this was part of the study in which the children could go on and off the medication per their parents’ desire, if they reached a clear state. If a child achieved a clear status, they would stay on the treatment for an additional three days. After that, they could stop treatment but could resume if the parents felt that their child’s symptoms were flaring. Children only had to come in for an unscheduled visit or to talk to the investigator if there was a tremendous swing. For example, if AD affected more than 20% of their body surface.
Q. What did the long-term results reveal about the efficacy of ruxolitinib cream when applied as needed in children aged 2–11 years?
We saw very good results all the way through to 52 weeks. At 8 weeks, 56% of the children achieved at least a two-point reduction in their Investigator’s Global Assessment (IGA) score, reaching a status of ‘clear’ or ‘almost clear.’ Additionally, 67.2% of the children showed significant improvement, achieving EASI-75 (a 75% reduction in the Eczema Area and Severity Index).
In this part of the study, we found that when children entered into the long term phase, they were able to maintain these very strong percentages of improvement. In the case of children who started the study on a placebo, we observed a rapid improvement once they switched to ruxolitinib cream. They were able to maintain this improvement, as indicated by their ‘clear’ or ‘almost clear’ skin status and by a reduction in affected body surface area.
Q. What was observed in terms of safety and tolerability of ruxolitinib cream in children?
Children did very well in this study. When we’re talking about a topical agent, we want to know whether it’s getting into the body, especially with a medication like ruxolitinib. Ruxolitinib carries a boxed warning due to theoretical risks considered linked to systemic absorption. These concerns are primarily based on studies involving topical tofacitinib and the potential for serious adverse effects once the medication is absorbed into the bloodstream. But in this study, as in other ruxolitinib studies, there really was no absorption. When we think about ruxolitinib given systemically, we consider 281 nanomolar to be the threshold by which JAK-mediated myelosuppression occurs in adults. In this study of children, that threshold was not reached, and only low plasma concentration levels were found in the blood for both ruxolitinib concentrations and throughout the study. So, I don’t think we need to be concerned, particularly when we’re keeping application to below 20% body surface area, which is what is on-label for this treatment.
In addition, when we looked at the laboratory tests, we did not see any evidence of any problems haematopoietically in terms of blood counts or any other unusual laboratory related findings.
With respect to any treatment-emergent adverse events, not much was reported, and certainly not much more than we would expect when considering individuals living with AD. There was one serious infection: a two-year-old developed eczema herpeticum, which certainly is within the spectrum of what we see with atopic dermatitis, but we can’t implicate the drug as causing this necessarily.
What we were all keeping an eye on was local side effects, such as those observed with current nonsteroidal anti-inflammatory medications, like the topical calcineurin inhibitors and topical phosphodiesterase four (PDE4) inhibitors. But in contrast to topical calcineurin inhibitors and crisaborole, there were no burning, stinging or other local application side effects reported in this study. In fact, there was a 1.1% overall application site reaction noted in this study, and if you look throughout the course of the year, only 3% of those receiving ruxolitinib cream developed signs suggestive of burning or stinging.
In summary, I think we have a very good topical drug here for children aged 2–11 years with mild to moderate AD. The treatment does not really get absorbed systemically and has a very low chance of causing burning and stinging, which is what we’re all seeing for our patients.
Q. How might these findings impact how we treat young patients with atopic dermatitis?
We’re all looking for topicals that don’t burn, sting, or cause reactions but we are also looking for nonsteroidal options. Why? Because particularly in sensitive areas, like the face and the genital area, potential adverse events from steroid treatments – as well as concerns of parents — can be problematic, particularly when using them long-term for maintenance therapy. So, having a nonsteroidal option — one that avoids the risks of local skin thinning or systemic absorption, doesn’t cause burning, stinging, or other local reactions, and is highly effective is a welcome addition.
References:
- Eichenfield LF, et al. A phase 3 study of ruxolitinib cream in children aged 2–<12 years with atopic dermatitis (TRuE-AD3): 8-week analysis. Presented at: 32nd European Academy of Dermatology and Venereology (EADV) Congress, Berlin, Germany, 11–14 October 2023.
- Papp K, et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies. J Am Acad Dermato. 2021 Oct;85(4):863-872
Associated abstract: Eichenfield L, et al. 52-week safety and disease control with ruxolitinib cream in children aged 2 to 11 years with atopic dermatitis: Results from the phase 3 TRuE-AD3 study. Presented at: 33rd European Academy of Dermatology and Venereology (EADV) Congress, Amsterdam, the Netherlands, 25–28 September 2024. Abstr 8082.
Speaker Disclosures: Prof. Amy Paller discloses consulting for Abeona, Apogee, Arcutis, Aslan, BioCryst, Boehringer-Ingelheim, Castle Creek, Bristol-Myers-Squibb, Dermavant, Incyte, Krystal, LEO, L’Oreal, Mitsubishi Tanabe, MoonLake Immunotherapeutics, Procter & Gamble, Regeneron, Sanofi, Seanergy, and UCB; grant/research support from AbbVie, Applied Pharma Research, Biomendics, Dermavant, Eli Lilly, Incyte, Janssen, Krystal, Regeneron, Timber and UCB; and service on the data safety monitoring board for AbbVie, Abeona and Galderma.
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Interviewer/Editor: Gina Furnival
Cite: Paller A. Ruxolitinib cream shows safe and lasting control in paediatric atopic dermatitis. touchDERMATOLOGY. November 18, 2024.
