What’s New in Topicals for Atopic Dermatitis?

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin condition that can have tremendous impact on quality of life for affected children and adults. First-line therapy for acute management of AD includes topical therapies such as corticosteroids, calcineurin inhibitors, and, more recently, the phosphodiesterase inhibitor crisaborole. Topical agents have remained the mainstay therapy for decades; however, there has been a longstanding need for topical therapies with high efficacy and low risk of adverse effects with long-term use. Given the ongoing advances in understanding the pathogenesis of AD, there are novel targets for pharmacological intervention. We are now in an unprecedented time with more than 40 topical treatments in the pipeline for AD in addition to many developments and treatments on the horizon. This review summarizes selected therapeutic topical agents in later phases of development that target various aspects in the pathogenesis of AD such as Janus kinase inhibition (ruxolitinib and delgocitinib), phosphodiesterase-4 inhibition (roflumilast and difamilast), aryl hydrocarbon modulation (tapinarof), and modulation of the microbiome. We also review novel targeted therapies that are in early phase clinical trials, including AMTX-100, BEN-2293, and PRN473. Preliminary findings on efficacy and tolerability of most of these agents are promising, but further studies are warranted to evaluate the long-term safety and efficacy of these novel agents against the current standard of care.

Oxidative Stress and Phototherapy in Atopic Dermatitis: Mechanisms, Role, and Future Perspectives

“…First-line therapy for the acute management of AD includes topical corticosteroids (TCS) whose long-term use is however limited by a plethora of possible side effects, including localized skin atrophy, telangiectasias, perioral dermatitis, and iatrogenic acne [ 26 ]. Hence, it derives non-steroidal alternatives, among them topical calcineurin inhibitors (TCIs), such as tacrolimus and pimecrolimus, which are approved for short-term or intermittent administration in patients who have previously failed on, or have contraindications to, TCSs [ 27 , 28 ].…”

“…TCIs lead to the inhibition of T cell activation and to the downregulation of pro-inflammatory cytokines, with a consequent immunosuppressive action [ 27 ]. TCIs can cause local adverse effects such as skin burning and irritation, even if they do not cause the risk of local atrophy [ 26 ]. Among the non-steroidal alternatives, phosphodiesterase 4 (PDE4) inhibitors are being largely used.…”

Oral orismilast: Efficacy and safety in moderate‐to‐severe psoriasis and development of modified release tablets

“…PDE4 inhibition downregulates proinflammatory cytokines including TNF‐α, interferon (IFN)‐gamma, IL‐4, IL5, IL‐6, IL‐8, IL‐13, IL‐17, IL‐22 and IL‐23 5–7 . Oral PDE4 inhibitors, including apremilast and roflumilast, are approved for the treatment of psoriasis and other chronic inflammatory diseases while crisaborole and difamilast have been launched for topical treatment of atopic dermatitis, and inhaled tanimilast is in phase 3 for treatment of COPD 8–10 . Hence, PDE4 inhibition is an established therapeutic target for chronic inflammatory diseases.…”

Anti-Inflammatory Effects Exerted by 14-Methoxyalternate C from Antarctic Fungal Strain Pleosporales sp. SF-7343 via the Regulation of NF-κB and JAK2/STAT3 in HaCaT Human Keratinocytes

“…Skin fragility and thinning, suppression of melanocytes and gastrointestinal side effects. Therefore, there is a need to find alternative strategies for the treatment of mild or moderate AD [ 3 , 4 , 5 ]. In many instances, skin diseases caused by infections or other tissue damage are indistinguishable from inflammation [ 6 ].…”