FDA Approves Roflumilast Cream for Pediatric Patients With Atopic Dermatitis

The Food and Drug Administration (FDA) approved the supplemental new drug application for roflumilast (Zoryve; Arcutis Biotherapeutics) cream 0.05% for the topical treatment of mild to moderate atopic dermatitis in children aged 2 to 5 years. This approval represents the sixth FDA approval for roflumilast cream 0.05% within the past 3 years, according to the manufacturer’s news release.¹

Roflumilast cream 0.05% is an advanced topical phosphodiesterase 4 (PDE4) inhibitor. It targets PDE4, an established target in dermatology and an intracellular enzyme that increases the production of proinflammatory mediators and decreases production of anti-inflammatory mediators. Once-daily roflumilast cream 0.05% provides rapid and significant clearance of atopic dermatitis anywhere on the body and offers health care professionals, parents, and caregivers of children aged 2 to 5 years an alternative to steroids that can be used for any duration.¹

“[Roflumilast cream 0.05%] was intentionally formulated to address the critical unmet need in atopic dermatitis care, and it provides a safe, effective alternative to steroid treatments, targeting the underlying inflammation that drives disease activity. Notably, [it] does not include ingredients known to compromise the skin barrier, which is especially important for young children with atopic dermatitis,” Frank Watanabe, president and CEO of Arcutis Biotherapeutics, said in a news release. “[Roflumilast cream 0.05%] provides patients and their families with a treatment option for long-term, continuous use, helping maintain clear skin and limiting cumulative topical steroid exposure.”¹

The approval is based on results from the phase 3 INTEGUMENT-PED (NCT04845620)², the INTEGUMENT-OLE long-term extension study (NCT04804605)³, and a phase 1 pharmacokinetic study.

What Did Researchers Learn in the INTEGUMENT-PED Trial?

INTEGUMENT-PED was a randomized, double-blind, vehicle-controlled, parallel-group study, that evaluated roflumilast cream 0.05% (n = 437) or vehicle (n = 215) once-daily for 4 weeks in 652 children aged 2 to 5 years. In the INTEGUMENT-PED trial, roflumilast cream demonstrated rapid disease clearance, with data showing significant improvements as early as week 1.

At week 4, approximately 25.4% of children treated with roflumilast cream 0.05% achieved a validated Investigator Global Assessment – Atopic Dermatitis (vIGA-AD) success, which is defined as a score of “clear” or “almost clear,” plus a 2-grade improvement from baseline, compared with about 10.7% of children treated with vehicle (P < .0001).^1,2

Additionally, the study also met all predetermined secondary end points, with improvements seen across all time points, including vIGA-AD of “clear” and “almost clear” at week 1. Additionally, about 39.4% of children using roflumilast cream achieved a 75% reduction in Eczema Area and Severity Index (EASI-75) at week 4 compared with 20% using vehicle, with differences observed as early as week 1 (exploratory endpoint). The investigational treatment was also shown to reduce itch at week 4, with some caregivers reporting less itching within 24 hours following the first application. In an exploratory analysis, over one-third of the children who had a baseline Worst Itch Numeric Scale (WI-NRS) score of 4 or higher (as reported by the caregiver) achieved a 4-point reduction in WI-NRS at week 4. In vehicle-treated children, this was achieved by 18% of patients. (nominal P = .0002).^1,2

What Did Researchers Learn in the INTEGUMENT-OLE Trial?

INTEGUMENT-OLE was a phase 3 multicenter, open-label extension study of the long-term safety and efficacy of roflumilast cream 0.15% in adults and children aged 6 years and older with atopic dermatitis and roflumilast cream 0.05% in children aged 2 to 5 years with atopic dermatitis. A total of 658 children and adults from 2 prior studies and 562 children from INTEGUMENT-PED enrolled in the INTEGUMENT-OLE study.^1,3

In INTEGUMENT-OLE, roflumilast cream treatment continued for up to 56 weeks. In addition to maintaining efficacy, roflumilast cream continued to improve, with approximately 71.9% of participants who rolled over from the roflumilast cream 0.05% treatment arm in the INTEGUMENT-PED trial achieving 75% improvement from baseline in EASI following 56 weeks of treatment. Starting at week 4 of INTEGUMENT-OLE, participants who achieved a vIGA-AD score of 0 (clear) switched to proactive twice-weekly application (n = 170; 30.2%). For those who switched to twice-weekly application, the median duration of disease control was 238 days (34 weeks), which was consistent with the 281 days observed for adults and children down to age 6 who used twice-weekly dosing with roflumilast cream 0.15%.^1,3

Roflumilast cream 0.05% was well-tolerated in the pivotal studies, with the most common adverse events reported in the clinical trials being upper respiratory tract infection, diarrhea, vomiting, rhinitis, conjunctivitis, and headache. Additionally, the safety profile of was generally consistent with continued treatment in INTEGUMENT-OLE.^1-3

“It is essential to have safe and effective treatments for children, who are often diagnosed with atopic dermatitis at a young age and can live with the condition across their lifetime. Young children often experience widespread disease, affecting large portions of their skin. Although topical steroids have been the standard treatment for years, they are not appropriate for long-term use,” INTEGUMENT study investigator Lawrence F. Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego, said in the news release. “With this approval, health care providers and families have an effective new treatment option for young children with atopic dermatitis.”¹

REFERENCES

1. Arcutis Biotherapeutics. FDA Approves Arcutis’ ZORYVE® (roflumilast) Cream 0.05% for the Treatment of Atopic Dermatitis in Children Ages 2 to 5. News release. October 6, 2025. Accessed October 6, 2025. https://www.arcutis.com/fda-approves-arcutis-zoryve-roflumilast-cream-0-05-for-the-treatment-of-atopic-dermatitis-in-children-ages-2-to-5/

2. Trial of PDE4 Inhibition With Roflumilast for the Management of Atopic Dermatitis (Integument-PED). ClinicalTrials.gov identifier: NCT04845620. Updated May 6 2024. Accessed October 6, 2025. https://clinicaltrials.gov/study/NCT04845620

3. Open Label Extension Trial of PDE4 Inhibition With Roflumilast for the Management of Atopic Dermatitis (INTEGUMENT-OLE). ClinicalTrials.gov identifier: NCT04804605. Updated May 11, 2025. Accessed October 6, 2025. https://clinicaltrials.gov/study/NCT04804605