New Non-Steroidal Topical Therapies for Inflammatory Dermatoses-Part 3: Roflumilast

Topical corticosteroids have remained the initial and long-term topical treatment option for inflammatory dermatitis conditions since the 1950s. A number of non-steroidal topicals for treatment of inflammatory dermatoses have been developed in the recent decades, such as topical calcineurin inhibitors (tacrolimus ointment and pimecrolimus cream), vitamin D analogues, and phophodiesterase-4 inhibitors (crisaborole), but none had the combination of broad therapeutic range, relatively rapid onset of action, tolerability, and wide-spread clinical success that allowed topical glucocorticosteroids to remain the mainstay of therapy. This situation has shifted dramatically with three non-steroidal new molecular entities, each with completely different mechanisms of action, receiving approval of the Food and Drug Administration (FDA) in the past year. Topical ruxolitinib, a Janus kinase (JAK) inhibitor, was the first to receive FDA approval, specifically for treating atopic dermatitis, and was the subject of the first report in this series. Subsequently, topical tapinarof, an aryl hydrocarbon receptor modulating agent, was approved by the FDA for treating plaque psoriasis in May 2022 and was the focus of the second report in this series. Finally, and most recently in July 2022, topical roflumilast, a highly potent phosphodiesterase-4 inhibitor, has received FDA approval for treating plaque psoriasis, and is the subject of the third and final report in this series. In addition to their unique mechanisms of action and spectra of activity, each of these agents has unique clinical characteristics, including degree of efficacy, rapidity of onset of efficacy, potential remittive effects, and safety and tolerability profiles. In this three-part series, we reviewed and summarized the data surrounding each agent, providing a comprehensive overview that would allow dermatologists to integrate them confidently and appropriately into treatment paradigms. Part three focuses on topical roflumilast, a highly potent phosphodiesterase-4 inhibitor.