Roflumilast Cream 0.05% Effective for Atopic Dermatitis in Patients Aged 2-5 Years

Roflumilast cream 0.05% is an effective, novel topical therapy option for pediatric patients aged 2–5 years suffering from mild-to-moderate atopic dermatitis, recent findings suggest.1

These data were the conclusion of the INTEGUMENT-PED study, during which investigators followed up the INTEGUMENT-1 and INTEGUMENT-2 phase 3 trials with a new study evaluating patients in a younger age range with roflumilast cream 0.05%.

This study was authored by a team led by Lawrence Eichenfield, MD, professor of dermatology and pediatrics at Rady Children's Hospital and the University of California, San Diego. Eichenfield et al. highlighted prior data from the INTEGUMENT-1 and 2 studies, during which positive findings resulted from treatment with roflumilast cream 0.15% among patients aged ≥ 6 years.2

“The efficacy and safety of once-daily roflumilast cream 0.05% among pediatric patients aged 2–5 years with mild-to-moderate [atopic dermatitis] enrolled in the INTEGUMENT-PED trial are reported here,” Eichenfield and colleagues wrote.1

Effects of Roflumilast Cream on Pediatric Patients

The investigative team of INTEGUMENT-PED conducted this phase 3, 4-week, parallel-group, vehicle-controlled, double-blind analysis with the aim of assessing roflumilast cream's efficacy and safety when administered to children in the age range of 2 - 5 years who suffer from mild-to-moderate atopic dermatitis. The team's analysis occurred in the US, Poland, and Canada across 109 sites between March 2021 - June 2023.

Individuals deemed eligible to participate as subjects in the trial were required to have experienced atopic dermatitis symptoms for 6 weeks at minimum and to have maintained a stable disease state for the prior 4 weeks. Those being considered for inclusion were also required to have a score of 2 in the Validated Investigator Global Assessment for atopic dermatitis (vIGA-AD) or a score of 3. They were also required to have an Eczema Area and Severity Index (EASI) score of 5 at least as well as at least 3% body surface area (BSA) impacted by the inflammatory condition.

The investigators randomly assigned eligible subjects in a 2:1 ratio to be treated either with roflumilast cream 0.05% or a vehicle cream, stratifying their randomization by baseline vIGA-AD severity (mild or moderate) and by trial site location. An internet-based response system was implemented by Eichenfield and colleagues to assign uniquely numbered medication kits with blinded containers of the cream, allocating the number of kits based on the affected BSA of the subject.

Application of roflumilast cream was done once each day by caregivers to all of the impacted areas. They were also instructed to apply it to any new regions that developed symptoms, except the scalp, as it had been excluded from treatment. The investigators did include palm and sole treatment, but these areas were not included in their assessment of efficacy.

vIGA-AD Success was a primary endpoint for the research team, defined as achieving a score of 0 (meaning 'clear') or 1 ('almost clear') and at least a 2-grade improvement from the point of baseline observable at the 4-week mark. EASI-75, representing ≥75% improvement in patients' EASI, was a secondary endpoint assessed by the team. Another secondary endpoint was Worst Itch-Numeric Rating Score (WI-NRS) Success, which the investigators noted is defined as a ≥4-point baseline score improvement. They also looked at roflumilast's safety and tolerability.

There were 437 individuals in the study who were treated with roflumilast cream, and there were 215 who were placed into the vehicle arm of the trial. The investigative team concluded that at the 4-week mark, a significantly higher proportion of those in the roflumilast arm visibly attained EASI-75 (39.4% versus 20.6%; P < 0.0001), vIGA-AD Success (25.4% versus 10.7%; P < .0001), and WI-NRS Success (35.3% versus 18.0%; nominal P = .0002).

In 1 notable finding in INTEGUMENT-PED, pruritus improvement was observed by the investigators within 24 hours of the cream's initial administration (nominal P = .0014). They also highlighted the notable infrequency of teatment-emergent adverse events (TEAEs) across both cohorts. At all time points, it was expressed that ≤0.7% of patients' caregivers in the roflumilast arm noted stinging or burning sensations that led to definite discomfort.

"These results suggest roflumilast cream 0.05% may provide a novel topical treatment option for patients aged 2–5 years with mild-to-moderate [atopic dermatitis]," they wrote.1

References

1. Eichenfield, L.F., Serrao, R., Berk, D.R., et al (2025). Efficacy and Safety of Once-Daily Roflumilast Cream 0.05% in Pediatric Patients Aged 2–5 Years With Mild-to-Moderate Atopic Dermatitis (INTEGUMENT-PED): A Phase 3 Randomized Controlled Trial. Pediatric Dermatology. https://doi.org/10.1111/pde.15840.

2. E. L. Simpson, L. F. Eichenfield, J. Alonso-Llamazares, et al., “Roflumilast Cream, 0.15%, for Atopic Dermatitis in Adults and Children: INTEGUMENT-1 and INTEGUMENT-2 Randomized Clinical Trials,” JAMA Dermatology 160 (2024): 1161–1170, https://doi.org/10.1001/jamadermatol.2024.