Lawrence Eichenfield, MD: Outlining Late-Breaking INTEGUMENT-PED Data for Roflumilast in Pediatric Patients

At the 2024 American Academy of Dermatology Annual Meeting, Lawrence Eichenfield, MD, shared a late-breaking clinical trial presentation on roflumilast cream 0.05% in children 2 to 5 years of age with atopic dermatitis from the pivotal INTEGUMENT-PED phase 3 randomized controlled trial.

Eichenfield, professor of dermatology and pediatrics at Rady Children's Hospital and the University of California San Diego, spoke with Dermatology Times to discuss the background and methods of the study, key takeaways for clinicians, and potential real-world and clinical implications of the study.

Transcript

Lawrence Eichenfield, MD: I'm Dr Larry Eichenfield. I'm a professor of dermatology and pediatrics at Rady Children's Hospital and the University of California San Diego, where I run the pediatric dermatology group, and I'm happy to be discussing the late-breaking presentation from the AAD on roflumilast cream 0.05%. This is a study in atopic dermatitis patients ages 2 to 5 years of age. This was the core phase 3 randomized control trial of the 0.05% cream in this young age group.

Dermatology Times: What are the background and methods behind the INTEGUMENT-PED study?

Eichenfield: We know roflumilast cream has been previously approved for psoriasis in patients 6 years of age of and older, a formulation approved for seborrheic dermatitis ages 9 and older, and the drug has previously been studied at the 0.15% concentration for atopic dermatitis in patients ages 6 and older. This study was looking at the 0.05% preparation of the roflumilast cream in 2 to 5 year olds. The study design was a pretty typical study designed.

First of all, the patients who were included in the study were 2 to 5 years of age with atopic dermatitis, but they had to have mild to moderate atopic dermatitis with a minimum body surface area of 3%, though most of them had much higher than that, a minimum EASI score of 5, and they were randomized 2:1 to the active roflumilast cream 0.05%, or vehicle cream. It was a 4-week, once a day dosing. Then the outcome measures were very traditional outcome measures for these kinds of studies: the percentage of patients who made it to clear and almost clear using the validated IGA score with at least a 2-step improvement, and secondary outcome measures were clear or almost clear, but not requiring the 2 steps. So if a mild patient made it to almost clear, that counts as almost clear, as well as the standard treatment success at earlier time points, week 2 and 1, and then that 75%, EASI 75% improvement at week 4, and then looking at pruritus scores, and of course, safety and tolerability, which is really crucial for a topical medication in these young children.

Dermatology Times: What are key takeaways for dermatology clinicians to consider about this study?

Eichenfield: They should know first of all, when it comes to the patients in this study, that these young children were racially and ethnically diverse, that they started off with a pretty high body surface area, with the average body surface area being about 22, but with a range up to 82% body surface area, and pretty significant itch score of around 6 at baseline, and EASI score was around 12. So it was a pretty affected patient population.

Then using the medicine once a day over a pretty short 4-week time period, about 25% of patients made it to the treatment success, clear or almost clear at 2 steps as compared to about 11% of the ones in the vehicle group, and that marked statistical significance at week 2 as well as week 1. So a quick response and consistent response.

Across the other outcome measures, that clear almost clear, it's around 35% as compared to 14% at week 4, with statistical significance earlier, as well. Almost 40% of patients had that 75% EASI improvement after 4 weeks of once a day application. And itch response, over 35% of patients had at least a 4-point drop, and it's very consistent outcome measures. It was very rapid decrease in itch with improvement as compared to the vehicle observed at 24 hours after application, the first time point that was asked.

Very, very importantly, the safety data was very consistent with what we've seen in the atopic dermatitis patients 6 years of age and older, which is very low adverse events. There was only one serious adverse event that wasn't considered to be associated with the drug, and very good levels of tolerability. There was a both an investigator-rated local tolerability assessment and a patient rated local tolerability assessment, and it showed very high rates of tolerability, which I think is very important in the young age group.

Dermatology Times: What are some real-world and clinical implications of this study?

Eichenfield: I think having a non-steroidal agent in a class of drug PDE4 inhibitors with the history of roflumilast studied showing very good safety data and good tolerability, and as a non-steroidal agent with good efficacy in this young age group, really is something that fits a clinical need, as we try to take care of patients and families, not just relying on topical corticosteroids, because it concerns them over time. I think we have the conclusions that there was there was good efficacy, good tolerance, and good safety. Also, I think it fits in with the prior INTEGUMENT-1 and 2 studies; there was about 40 to 43% had that EASI75 response. So we're getting a consistent sense of the efficacy of the drug in the atopic dermatitis population, expanding it beyond seborrheic dermatitis and psoriasis.

[Transcript has been edited for clarity.]