Roflumilast cream 0.05% shows early AD clearance in infants

Once-daily roflumilast cream 0.05% (Zoryve; Arcutis Biotherapeutics) was well tolerated and showed early disease improvement in infants aged 3 to less than 24 months with atopic dermatitis (AD). The data come from the phase 2 INTEGUMENT-INFANT study, presented at the 35th European Academy of Dermatology and Venereology (EADV) Congress in Vienna, Austria.¹ The FDA is currently reviewing a supplemental New Drug Application (sNDA) to extend the cream's AD indication to this age group. Its Prescription Drug User Fee Act (PDUFA) target action date is February 23, 2027.¹^,²

"The results include positive data for once-daily ZORYVE cream in infants ages 3 to 24 months with atopic dermatitis," said Frank Watanabe, president and CEO of Arcutis. He described infants as among "the most vulnerable and underserved patient populations."¹

INTEGUMENT-INFANT safety and efficacy of roflumilast cream 0.05% in infants with AD

INTEGUMENT-INFANT was an open-label study that enrolled 101 infants with mild to moderate AD. Participants applied roflumilast cream 0.05% once daily for 4 weeks. Its primary objective was safety and tolerability, and efficacy was exploratory.² A separate open-label phase 1 pharmacokinetic study enrolled 19 infants in the same age range.²

In the poster (P2401) presented by Lawrence F. Eichenfield, MD, and colleagues, no serious adverse events occurred. At least 97.9% of infants showed no evidence of application-site irritation.¹ The most frequently reported adverse events were diarrhea, nasopharyngitis, upper respiratory tract infection, and vomiting. No new safety signals emerged relative to studies in children aged 2 to 5 years.²

Of the 96 infants who completed 4 weeks of treatment, 34.4% achieved Validated Investigator Global Assessment for AD (vIGA-AD) success. Success was defined as a score of clear or almost clear with at least a 2-grade improvement from baseline.¹ IGA-Scalp success, defined the same way, was reached by 67.5% of infants.¹ For itch, caregivers used the Dynamic Pruritus Scale (n = 88). On that measure, 46.6% of infants had at least a 25% improvement in itch within 10 minutes of application.¹

Roflumilast pediatric AD labeling and PDE4 inhibitor mechanism

Roflumilast is a topical phosphodiesterase type 4 (PDE4) inhibitor that reduces production of proinflammatory mediators in the skin.¹ The 0.05% cream is approved for mild to moderate AD in children aged 2 to 5 years. The 0.15% cream is approved for patients 6 years and older.¹ The approval for children aged 2 to 5 years rested on INTEGUMENT-PED, a phase 3, double-blind, vehicle-controlled trial. In that trial, 25.4% of 437 children treated with roflumilast achieved vIGA-AD success at week 4, compared with 10.7% of 215 children who received vehicle (P < .001).³

Caregiver survey highlights topical corticosteroid hesitancy in children with chronic skin disease

The company also presented real-world survey data at the Fall Clinical Dermatology Conference in Las Vegas, Nevada. The survey was developed with the National Eczema Association and the National Psoriasis Foundation. It included 500 caregivers of children prescribed topical corticosteroids for AD, psoriasis, or seborrheic dermatitis.¹

In the analysis by Simpson et al., 77.6% of caregivers agreed that their child's treatment focused on reacting to flares rather than long-term control. In addition, 32.8% reported that their child had uncontrolled symptoms at least weekly.¹ Even when symptoms were controlled, 54.8% of caregivers reported anxiety that they would worsen again.¹

A companion analysis by Bhutani et al found that 45.0% of caregivers hesitated to raise concerns about long-term steroid use with their child's clinician.¹ Hesitancy was more common among caregivers whose child had a prior negative reaction to a corticosteroid (57.0% vs 34.6%). It was also more common when a child had been prescribed more than 1 corticosteroid (53.9% vs 38.2%).¹

Limitations of INTEGUMENT-INFANT and next steps for infant AD treatment

INTEGUMENT-INFANT had no vehicle arm and lasted only 4 weeks. Because of this, its response rates cannot be separated from the natural fluctuation of AD. They also should not be compared directly with the vehicle-controlled INTEGUMENT-PED results. The rapid itch findings relied on caregiver report, and long-term safety in infants remains uncharacterized.

The survey data are also limited. They were self-reported, cross-sectional, and sponsor-supported, so they describe caregiver perceptions rather than clinical outcomes. They do not show whether nonsteroidal alternatives improve adherence or disease control in children. The FDA's decision on the infant indication is expected by February 23, 2027.²

References

1. Arcutis Biotherapeutics. Arcutis presents ZORYVE (roflumilast) data and real-world topical corticosteroid research at EADV and Fall Clinical. GlobeNewswire. October 9, 2026. Accessed October 9, 2026. https://www.globenewswire.com/news-release/2026/10/09/3378045/0/en/arcutis-presents-zoryve-roflumilast-data-and-real-world-topical-corticosteroid-research-at-eadv-and-fall-clinical.html

2. Arcutis Biotherapeutics. FDA accepts supplemental New Drug Application for Arcutis' ZORYVE (roflumilast) cream 0.05% for the treatment of mild to moderate atopic dermatitis in infants down to 3 months. GlobeNewswire. July 8, 2026. Accessed October 9, 2026. https://www.globenewswire.com/news-release/2026/07/08/3324020/0/en/fda-accepts-supplemental-new-drug-application-for-arcutis-zoryve-roflumilast-cream-0-05-for-the-treatment-of-mild-to-moderate-atopic-dermatitis-in-infants-down-to-3-months.html

3. Eichenfield LF, Serrao R, Prajapati VH, 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. Pediatr Dermatol. 2025;42(2):296-304. doi:10.1111/pde.15840