Topical PDE-4 Inhibitors for the Management of Immune-Mediated Inflammatory Skin Conditions

On the first day of Fall Dermatology Week 2023, April Armstrong, MD, MPH, discussed ongoing challenges with managing common immune-mediated inflammatory skin diseases (IMIDs), such as psoriasis, and the evolving role of topical phosphodiesterase-4 (PDE-4) inhibitors in their management during her session, “The Evolving Role of Topical PDE-4 Inhibitors for the Management of Immune-Mediated Inflammatory Skin Conditions.”

To start, Dr Armstrong listed her objectives, which included understanding the mechanism of action of PDE-4 inhibitors and looking at the efficacy and safety data associated with the current and emerging PDE-4 inhibitors, specifically the topicals, for the management of IMIDs.

Dr Armstrong continued, “We know that topical therapies have really been the cornerstone of treatment of many of our patients with psoriasis, atopic dermatitis, or seborrheic dermatitis. Importantly, we also know from our patients, there is a continual need for topical therapies that are nonsteroidal.”

She noted that an opportunity exists for the development of well-tolerated and effective topical therapies for IMIDs. She shared that newer nonsteroidal topical options include aryl hydrocarbon receptor inhibitors and especially PDE4 inhibitors. She delved into the mechanism of action behind PDE-4 inhibitors, showcasing cyclic adenosine 3′,5′-monophosphate (cAMP) intracellularly and how PDE-4 converts cAMP to adenosine monophosphate (AMP), which results in a buildup of cyclic AMP inside the cell.

“The downstream effects of that include the inhibition of inflammatory mediators and also downregulation of macrophages and neutrophils,” she shared.

She proceeded to highlight PDE-4 inhibitors that may be more familiar to physicians, such as crisaborole, apremilast, and roflumilast. She shared that the PDE-4 inhibitor roflumilast is US Food and Drug Administration approved in a creamy vehicle for adolescents and adults with plaque psoriasis. Crisaborole is a 2% ointment approved for patients as young as age 3 months with mild to moderate atopic dermatitis. Finally, she showcased apremilast, noting that it has a stronger affinity with the PDE-4 A1A isoform than apremilast.

For more meeting coverage, visit the Fall Dermatology Week 2023 newsroom.

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Reference
Armstrong A. The evolving role of topical PDE-4 inhibitors for the management of immune-mediated inflammatory skin conditions. Presented at: Dermatology Week 2023; September 20-23, 2023; Virtual.