Evolving utility of apremilast in dermatological disorders for off-label indications

Abstract

Apremilast, a small molecule that acts by inhibition of the phosphodiesterase‐4 enzyme, has been approved by the US Food and Drug Administration for the management of psoriatic arthritis, plaque psoriasis and Behçet disease. The drug has drawn much interest from practising dermatologists in view of its exceptional safety profile and prescription convenience, as evident by the recent surge of literature describing its off‐label indications. This review was carried out with the aim of summarizing the literature on off‐label use of apremilast in dermatology, in order to guide clinicians regarding currently available evidence. The PubMed database was searched using ‘apremilast’ as a keyword in the title. Abstracts were individually screened to determine whether there was a description of an off‐label use of apremilast in dermatology within the article. Randomized controlled trial data were available for vitiligo, alopecia areata, hidradenitis suppurativa and atopic dermatitis. Case series and case reports describing apremilast were also reviewed. Owing to its broad spectrum of immunomodulatory activity, apremilast may be useful in several chronic inflammatory skin diseases recalcitrant to conventional therapies, either alone or in combination with other drugs. Further studies are needed to establish its role in various dermatological indications.

Advances in the Study of PDE4 Inhibitors in Dermatological Disorders

“…By cross-linking with T cell membranes (e.g. CD4-positive and TH2 subsets), c-AMP can also inhibit T cell proliferation by acting as a regulator of T cells [7]. In terms of inflammatory regulation, PDE-4 may be involved in the regulation of eosinophil and neutrophil chemotaxis and degranulation [7,8].…”

“…CD4-positive and TH2 subsets), c-AMP can also inhibit T cell proliferation by acting as a regulator of T cells [7]. In terms of inflammatory regulation, PDE-4 may be involved in the regulation of eosinophil and neutrophil chemotaxis and degranulation [7,8]. These effects are mediated by PDE-4-mediated increases in IL-8, leukotriene B4 and superoxide anion levels in neutrophils.…”

“…The PDEs superfamily is divided into 11 species, ranging from PDE1-PDE11 [6]. PDE-4 is currently the most diverse subfamily of PDEs and is widely expressed in a variety of cell types [6,7]. These enzymes are intimately involved in a variety of physiological activities such as brain function, phagocyte/monocyte activation, cardiomyocyte contraction, vascular smooth muscle proliferation and neutrophil infiltration, to name a few.…”

cAMP: A master regulator of cadherin‐mediated binding in endothelium, epithelium and myocardium

“…In pemphigus, additional mechanisms may regulate Dsg internalization and p38MAPK signaling. The broad clinical application of PDE4 inhibitors such as apremilast in skin diseases may suggest that adrenergic signaling also is important for modulation of keratinocyte biology in other diseases 229 . For instance, coincidences of psoriasis and pemphigus and elevated risk in psoriasis patients to become affected by pemphigus may argue for similar mechanisms driving pathogenesis 230–232 …”

Apremilast Add-On Benefits Over Conventional Drugs (ABCD) in Unstable Non-segmental Vitiligo: A 12-Week Single-Center Randomized Controlled Trial

“…Both genders are equally affected, having no apparent differences in the rate of occurrence as per skin type or race. Current management includes topical and systemic glucocorticoids, topical calcineurin inhibitors, antioxidants, and narrowband ultraviolet B phototherapy used to promote re-pigmentation; they all have varying degrees of success and adverse effects associated [9,10]. Hence, alternative and more efficacious therapies with better safety profiles for prolonged use are needed to treat vitiligo.…”