Roflumilast Cream 0.15% Demonstrates Safety, Tolerability in Individuals With Atopic Dermatitis With Prior Treatment Failures

Roflumilast cream 0.15% demonstrated a favorable safety and tolerability profile in individuals with atopic dermatitis (AD) who previously experienced inadequate response, intolerance, or contraindications to standard topical treatments, according to a pooled subgroup analysis of phase 3 trials presented at the 2025 Revolutionizing Atopic Dermatitis Conference in Nashville, TN.

Led by Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, the analysis included 1,337 participants from the INTEGUMENT-1 and INTEGUMENT-2 phase 3 trials. Among participants, 39.2% reported prior unsatisfactory response to topical corticosteroids, 18.1% to topical calcineurin inhibitors, and 7.3% to crisaborole. Roflumilast maintained a consistent risk-benefit profile across these subgroups, with application-site tolerability matching that of the overall study population.

Treatment-emergent adverse events (TEAEs) occurred in 21.9% of participants treated with roflumilast compared with 14.4% of those receiving vehicle. Most events were mild or moderate, and serious adverse events occurred in fewer than 2% of participants across roflumilast subgroups. The most frequently reported TEAEs included headache, nausea, diarrhea, vomiting, and application-site pain. Application-site pain occurred in 1.5% of roflumilast-treated participants versus 0.7% in the vehicle group.

Roflumilast addresses a therapeutic need for individuals with AD who are intolerant to existing topical therapies, which may cause side effects or fail to control symptoms, both of which potentially impact treatment adherence and disease management. Topical corticosteroids, for example, are associated with local and systemic adverse effects, are not approved for long-term use, and may pose higher absorption risks in thin-skinned areas, the authors wrote.

Roflumilast is a topical phosphodiesterase 4 (PDE4) inhibitor formulated as a water-based, fragrance-free cream, free from known cutaneous irritants. It received FDA approval for patients aged ≥6 years with AD based on efficacy and safety data from the INTEGUMENT-1 (NCT04773587) and INTEGUMENT-2 (NCT04773600) trials.

These randomized, double-blind, vehicle-controlled trials enrolled participants aged ≥6 years with mild-to-moderate AD. Moderate disease (VIGA-AD score 3) was reported in 76.1% of participants, with a mean body surface area involvement of 13.5% and a mean EASI score of 10.1. Facial involvement was seen in 41.9% of participants, including eyelid involvement in 20.1%. Baseline characteristics and demographics were similar across treatment arms, with a mean age of 27.9 years (range 6–91), 55.3% women, and 82.6% identifying as non-Hispanic.

Application-site tolerability was high, according to Simpson, et al. Investigators reported no irritation in ≥95% of participants treated with roflumilast at all points in time, and ≥91% of reported no or mild sensation at the application site by week 4.

Efficacy outcomes showed improvement across key endpoints in patients with previous treatment difficulties. By week 4, VIGA-AD success rates (clear or almost clear) reached 41.1% in the overall roflumilast group. EASI-75 response was achieved by 42.7% of roflumilast-treated patients, with subgroup rates of 39.1% for those with prior corticosteroid issues, 40.9% for calcineurin inhibitor intolerance, and 40.2% for previous crisaborole users.

Improvements in quality of life, measured by DLQI/CDLQI minimal important difference, were observed in 40.7% of roflumilast patients compared to 30.9% receiving vehicle. Subgroup response rates were 43.3% for prior corticosteroid users, 23.3% for calcineurin inhibitor users, and 52.4% for those with prior crisaborole exposure.

Simpson and colleagues concluded that roflumilast cream 0.15% provides a consistent safety and efficacy profile across subgroups of patients with prior intolerance or inadequate response to topical treatments. These findings support roflumilast as an alternative for individuals with AD who cannot use standard topical therapies, helping to address an unmet clinical need.

Source: Simpson E, Eichenfield LF, Gooderham MJ, et al. Pooled safety and local tolerability of roflumilast cream 0.15% from the INTEGUMENT-1 and
INTEGUMENT-2 phase 3 trial of patients wtih atopic dermatitis: subgroup analysis of patients with prior inadequate response, intolerance, and/or contraindications to topical treamtents. Poster presented at Revolutionizing Atopic Dermatitis; June 6-7, 2025; Nashville, TN.