Roflumilast Cream, 0.15%, for Atopic Dermatitis in Adults and Children INTEGUMENT-1 and INTEGUMENT-2 Randomized Clinical Trials

Simpson EL, Eichenfield LF, Alonso-Llamazares J et al. JAMA Dermatol. 2024;160(11):1161-1170. doi:10.1001/jamadermatol.2024.3121

Key Points

Question  What is the efficacy and safety of once-daily roflumilast cream, 0.15%, in patients with atopic dermatitis (AD)?

Findings  In 2 phase 3 randomized clinical trials of 1337 individuals with AD, significantly more patients treated with once-daily roflumilast cream, 0.15%, achieved Validated Investigator Global Assessment for Atopic Dermatitis success at 4 weeks than patients treated with vehicle cream. Roflumilast was well tolerated with low rates of adverse events in both trials.

Meaning  An effective, well-tolerated, once-daily, nonsteroidal treatment like roflumilast cream, 0.15%, may address several unmet needs and substantially improve the treatment landscape for patients with AD.

Abstract

Importance  Safe, effective, and well-tolerated topical treatment options available for long-term use in patients with atopic dermatitis (AD) are limited and associated with low adherence rates.

Objective  To evaluate efficacy and safety of once-daily roflumilast cream, 0.15%, vs vehicle cream in patients with AD.

Design, Setting, and Participants  Two phase 3, randomized, double-blind, vehicle-controlled trials (Interventional Trial Evaluating Roflumilast Cream for the Treatment of Atopic Dermatitis 1 and 2 [INTEGUMENT-1 and INTEGUMENT-2]), included patients from sites in the US, Canada, and Poland. Participants were 6 years or older with mild to moderate AD based on Validated Global Assessment for Atopic Dermatitis (assessed on a 5-point scale ranging from 0 [clear] to 4 [severe]).

Intervention  Patients were randomized 2:1 to receive roflumilast cream, 0.15%, or vehicle cream once daily for 4 weeks.

Main Outcomes and Measures  The primary efficacy end point was Validated Investigator Global Assessment for Atopic Dermatitis success at week 4, defined as a score of 0 or 1 plus at least a 2-grade improvement from baseline. Secondary end points included Eczema Area and Severity Index and Worst Itch Numeric Rating Scale. Safety and local tolerability were also evaluated.

Percentage of Patients Achieving vIGA-AD Success
and at Least 75% Improvement in EASI Score

Results  Among 1337 patients (654 patients in INTEGUMENT-1 and 683 patients in INTEGUMENT-2), the mean (SD) age was 27.7 (19.2) years, and 761 participants (56.9%) were female. The mean body surface area involved was 13.6% (SD = 11.6%; range, 3.0% to 88.0%). Significantly more patients treated with roflumilast than vehicle achieved the primary end point (INTEGUMENT-1: 32.0% vs 15.2%, respectively; P < .001; INTEGUMENT-2: 28.9% vs 12.0%, respectively; P < .001). At week 4, statistically significant differences favoring roflumilast also occurred for the achievement of at least 75% reduction in the Eczema Area and Severity Index (INTEGUMENT-1: 43.2% vs 22.0%, respectively; P < .001; INTEGUMENT-2: 42.0% vs 19.7%, respectively; P < .001). Roflumilast was well tolerated with low rates of treatment-emergent adverse events. At each time point, investigators noted no signs of irritation at the application site in 885 patients who were treated with roflumilast (≥95%), and 885 patients who were treated with roflumilast (90%) reported no or mild sensation at the application site.

Conclusions and Relevance  In 2 phase 3 trials enrolling adults and children, once-daily roflumilast cream, 0.15%, improved AD relative to vehicle cream, based on multiple efficacy end points, with favorable safety and tolerability.

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