Phase 3 Trial Supports Roflumilast for Pediatric AD

Image Credit: © DermNet

Today, Arcutis Biotherapeutics announced positive results from the INTEGUMENT-PED phase 3 clinical trial evaluating the efficacy and safety of roflumilast (Zoryve) cream 0.05% for mild to moderate atopic dermatitis (AD) in children 2 to 5 years old. According to a news release from the company, the findings suggest that roflumilast may serve as an effective, steroid-free treatment for patients within this population.¹

“AD is a chronic, inflammatory skin disease affecting 1.8 million children ages 2 to 5 in the United States with burdensome symptoms that often result in impaired quality of life for both patients and their caregivers,” said Lawrence F. Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego and lead author on the publication, in the release. “Results from the INTEGUMENT-PED trial demonstrate that [roflumilast] cream 0.05% can quickly and reliably improve the symptoms of AD, especially itch. The publication of these results and the entire clinical development program highlight that [roflumilast] cream 0.05%, if approved, could fill a significant gap in the current treatment landscape for a once-daily steroid-free topical therapy that is appropriate for both the short and long-term management of AD, key concerns for young patients and their caregivers.”

Study Design and Methodology

The INTEGUMENT-PED trial was a multicenter, phase 3, randomized, double-blind, vehicle-controlled study designed to evaluate the efficacy and safety of roflumilast cream 0.05% in pediatric patients aged 2 to 5 years with mild to moderate AD. A total of 652 children were enrolled and randomized in a 2:1 ratio to receive either roflumilast cream 0.05% or a vehicle control, applied once daily for 4 weeks. Key inclusion criteria included a baseline validated Investigator Global Assessment–Atopic Dermatitis (vIGA-AD) score of 2 or 3 and an Eczema Area and Severity Index (EASI) score consistent with mild to moderate disease. The primary efficacy endpoint was vIGA-AD Success, defined as a vIGA-AD score of "Clear" or "Almost Clear" with a minimum 2-grade improvement from baseline at week 4.²

Efficacy Results

The news release stated that study results demonstrated statistically significant improvements in primary and secondary efficacy endpoints including:

• vIGA-AD Success: Researchers found 25.4% of patients in the roflumilast-treated group achieved vIGA-AD Success, compared to 10.7% in the vehicle group (p<0.0001).
• EASI-75 Response: 39.4% of children treated with roflumilast achieved a 75% reduction in EASI score compared to 20.6% in the vehicle group (p<0.0001), with researchers observingsignificant improvements as early as week 1.
• Pruritus Reduction: Rapid improvement in pruritus was observed, with 35.3% of children achieving a 4-point reduction in WI-NRS scores by week 4, compared to 18.0% in the vehicle group (p=0.0002). Improvement in itch was noted within 24 hours post-application.

Safety and Tolerability

Researchers found that roflumilast cream 0.05% was well-tolerated, with a low incidence of treatment-emergent adverse events. The most frequently reported adverse events (≥2%) included upper respiratory tract infection, diarrhea, and vomiting, with no individual adverse event occurring in more than 4.1% of patients. The overall safety profile was consistent with prior studies evaluating higher concentrations of roflumilast cream in older pediatric and adult populations. The study stated the low systemic absorption of topical roflumilast may contribute to its favorable safety profile compared to systemic PDE4 inhibitors.

Clinical Implications

Researchers stated the INTEGUMENT-PED trial provides compelling evidence supporting the efficacy and safety of roflumilast cream 0.05% as a non-steroidal treatment option for mild to moderate AD in young children. Its rapid onset of action, significant antipruritic effects, and favorable safety profile suggest potential advantages over traditional topical therapies. Moreover, the once-daily dosing regimen may enhance adherence among pediatric patients and caregivers. However, long-term studies evaluating the durability of response and safety beyond the 4-week treatment period remain warranted.

“On the heels of our recent submission of a sNDA to the FDA for [roflumilast] cream 0.05%, we’re proud to share the full INTEGUMENT-PED results published in Pediatric Dermatology with the dermatology community, supporting the well-established efficacy, safety, and tolerability profile of this lower concentration of [roflumilast] cream,” said Patrick Burnett, MD, PhD, FAAD, chief medical officer at Arcutis, in the release. “We’re committed to bringing forth meaningful innovation and addressing the significant unmet need for topical treatments of young children living with the challenges of AD. We look forward to the FDA’s potential approval of [roflumilast] cream 0.05% anticipated later this year.”

Conclusion

The findings from the INTEGUMENT-PED trial underscore the potential role of roflumilast cream 0.05% in the evolving therapeutic landscape of pediatric AD. If approved, this PDE4 inhibitor could offer clinicians an effective, well-tolerated, and steroid-free alternative for the management of AD in children aged 2 to 5 years. The study stated that future research should focus on long-term safety data, combination therapy strategies, and comparative effectiveness against existing treatment modalities to further delineate its clinical utility.

References

1. Arcutis announces publication of positive data from INTEGUMENT-PED trial evaluating ZORYVE® (roflumilast) cream 0.05% in children 2 to 5 years old with mild to moderate atopic dermatitis in pediatric dermatology. News release. Arcutis Biotherapeutics. Published February 24, 2025. Accessed February 24, 2025. https://www.arcutis.com/arcutis-announces-publication-of-positive-data-from-integument-ped-trial-evaluating-zoryve-roflumilast-cream-0-05-in-children-2-to-5-years-old-with-mild-to-moderate-atopic-dermatitis-in-pediat/
2. Eichenfield L, Serrao R, Prajapati V, et al. 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. 2025. doi:10.1111/pde.15840