Roflumilast Cream 0.05% Durable, Safe for Younger Pediatric Patients

Roflumilast cream 0.05% for atopic dermatitis demonstrated durable efficacy, and pediatric patients aged 2 to 5 years exhibited long-term tolerability of the phosphodiesterase-4 inhibitor for over 1 year (56 weeks) in the phase 3 INTEGUMENT-OLE trial (NCT04804605), with the improvements seen by week 4 in the parent analysis, INTEGUMENT-PED (NCT04845620), either maintained or improved. These results were presented in a poster at the recent Society for Pediatric Dermatology Annual Meeting.1

The phase 3 INTEGUMENT-PED trial evaluated the efficacy and safety of roflumilast cream 0.05% in children aged 2 to 5 years over 4 weeks of treatment. Compared with topical corticosteroids (TCS), which are known to be harsher against skin and have significant systemic absorption, roflumilast cream 0.05% does not contain propylene glycol, formaldehyde, fragrances, or potential cutaneous irritants.2 Patients were able to enroll in the open-label extension if they finished any of its 4-week parent trials with no safety concerns: INTEGUMENT-PED, INTEGUMENT-1 (NCT04773587), or INTEGUMENT-2 (NCT04773600).

In INTEGUMENT-OLE, roflumilast cream 0.05% was applied once daily for up to 52 weeks, with participants who turned age 6 during the study able to switch to roflumilast cream 0.15% on the first visit after their birthday. After week 4, if patients had reached a score of clear (0) on the Validated Investigator Global Assessment for Atopic Dermatitis scale (vIGA-AD), they could switch to twice-weekly application; this was maintained as long as signs and symptoms were adequately controlled and vIGA-AD remained clear or almost clear (0/1), the authors wrote.

The INTEGUMENT-PED study investigated the efficacy and safety of once-daily roflumilast cream 0.05% for atopic dermatitis in children aged 2 to 5 years. | Image Credit: © luchschenF-stock.adobe.com

The enrolled patients—382 in the treatment group and 180 who received vehicle cream—showed an overall high level of application-site tolerability, with more than 98% reporting no or minimal irritation and 97% and higher reporting no irritation for the duration of the open-label extension. In addition, 54.2% of patients demonstrated improvement via vIGA-AD scale improvement, 63.1% achieved vIGA-AD 0/1 (clear or almost clear skin), 73.3% achieved a 75% or greater reduction in their Eczema Area and Severity Index score (EASI-75), and 60.7% saw improvement on the Worst Itch Numeric Rating Scale (WI-NRS), which measures itch intensity over 24 hours on a scale of 0 (no itch) to 10 (worst itch).3

There were few cases of treatment-related adverse events (AEs) (2.5%) and no treatment-related serious AEs, although 3.2% did report a serious AE. Just 3.2% of patients discontinued roflumilast because of an AE, with the most common being upper respiratory tract infection (8.7%).

Approximately a third of patients (30.2%) switched to twice-weekly application after achieving vIGA-AD 0, and throughout this group, their median duration of disease control was 34 weeks (238 [95% CI, 146-331] days).

The overall mean (SD) patient age was 3.3 (1.1) years, and at baseline, 50.9% of patients were male at birth, 82.7% were not Hispanic or Latino, 66.5% had Fitzpatrick skin type I-III, 78.5% were vIGA-AD 3 (moderate) at enrollment, 52.8% had a history of inadequate response/intolerance/contraindication to TCS, and mean EASI, body surface area, and WI-NRS measures were 12.2 (10.2), 22.3% (17.5), and 6.1 (6.0), respectively.

The study authors note that their findings echo similar results seen among adult patients in previous analyses, thereby suggesting “that roflumilast cream is a long-term treatment option for those with AD, with the potential to switch to twice-weekly proactive application.”

References

1. Eichenfeld LF, Gonzalez ME, Boguniewiczet al. Once-daily/proactive twice-weekly roflumilast cream 0.05% in 2–5-year-olds with atopic dermatitis: long-term safety and efficacy. Presented at: Society for Pediatric Dermatology Annual Meeting; July 23-26, 2025; Seattle, WA. Poster POS-13.
2. Draelos ZD, Higham RC, Osborne DW, Seal MS, Burnett P, Berk DR. Assessment of the vehicle for roflumilast cream compared to a ceramide-containing moisturizing crem in mild eczema. J Drugs Dermatol. 2024;23(10):834-840. doi:10.36849/JDD.2024.7958
3. Worst Itch/Pruritus Numeric Rating Scale (WI‑NRS/WP‑NRS). USDermEd. Accessed August 15, 2025. https://www.usdermed.com/clinical-tools/wi-nrs