Roflumilast safe, tolerable in atopic dermatitis, including with facial involvement

Roflumilast cream 0.15% and 0.05% demonstrated consistent efficacy across endpoints and a favorable tolerability and safety profile in the treatment of adults and adolescents with mild to moderate atopic dermatitis, according to a study.

“Most patients with mild to moderate topical AD are treated with topical anti-inflammatory therapy — corticosteroids or calcineurin inhibitors — in combination with emollients,” Melinda J. Gooderham, MS, MD, of the SKiN Center for Dermatology, Probity Medical Research and Queen’s University, Peterborough, Ontario, Canada, and colleagues wrote. “However, side effects and poor adherence limit long-term use of topical corticosteroids, particularly on the face and other sensitive areas.”

In this phase 2, parallel-group, double-blind, vehicle-controlled study, Gooderham and colleagues assessed the safety and efficacy of roflumilast cream, a once-daily, non-steroidal topical phosphodiesterase-4 inhibitor, in patients aged 12 years and older with mild to moderate AD.

A total of 136 patients (mean age, 42.4 years; 64.4% female; 71.1% white) were randomly assigned to receive roflumilast 0.15%, roflumilast 0.05% or vehicle cream once daily for 4 weeks.

The researchers defined the primary endpoint as the absolute change in EASI score from baseline to week 4. Results showed this endpoint was achieved in both roflumilast 0.15% (–6.4) and 0.05% (–6) compared with vehicle (–4.8); however, the researchers said the change did not reach statistical significance by week 4.

The roflumilast creams outperformed vehicle in most secondary endpoints as well, with a 75% improvement in EASI score achieved by week 4 in 52.3%, 59.1% and 31.1% of the roflumilast 0.15%, roflumilast 0.05% and vehicle groups, respectively.

Of the roflumilast-treated patients, 52.3% of the roflumilast 0.15% group and 50% of the roflumilast 0.05% group achieved validated IGA-AD scores of “clear” or “almost clear” compared with 31.1% of the vehicle group.

Patients treated with roflumilast 0.15% experienced the most treatment-emergent adverse events at 26.7%, followed by 21.7% of roflumilast 0.05% patients and 13.3% of vehicle patients. All adverse events were mild or moderate in severity with the most common being sinusitis, urinary tract infection, headache and dry eye.

Treatment-related adverse events occurred in four patients — two receiving roflumilast 0.05% and two receiving vehicle — and included mild rash and moderate application site pain. One roflumilast patient discontinued treatment due to worsening AD.

The researchers called the small number of participants a study limitation.

“Roflumilast cream demonstrated a favorable safety and tolerability profile in patients with AD, including patients with facial involvement, and consistent efficacy across multiple endpoints,” Gooderham and colleagues wrote. “However, evaluation in larger clinical trials is required to better characterize safety and efficacy.”