Addressing treatment challenges in atopic dermatitis with novel topical therapies

Abstract

Atopic dermatitis (AD), a chronic inflammatory skin disease affecting children and adults, presents as mildto-moderate disease in the majority of patients. Pruritus, one of the key diagnostic criteria for AD, is associated with reduced quality of life and disease aggravation. Current treatments include emollients and topical pharmaceutical agents. Topical corticosteroids (TCSs) are commonly used, but are associated with safety concerns with cutaneous and systemic side effects. Topical calcineurin inhibitors (TCIs) inhibit T-lymphocyte activation, but their use is limited because of application-site infections and a boxed warning for potential malignancy risk. Despite recent reports indicating there is no malignancy risk, long-term treatment with TCIs is still considered with hesitancy. In addition, while both TCSs and TCIs provide some relief of pruritus, it often takes over a week for improvement to occur. The development of a more specific anti-inflammatory treatment which is easy to use and targets pruritus could provide clinically meaningful improvements for patients with AD. The majority of emerging therapies for AD are focused on inhibiting phosphodiesterase 4 (PDE4), an enzyme which is increased in inflammatory disorders such as AD. This review will update readers on the recent advances in topical therapies, including PDE4 inhibitors, for the treatment of AD. ARTICLE HISTORY

Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical t

“…CsA suppresses Th1, Th2 and Th17/22, affecting both humoral and cellular immune responses . Long‐term use (beyond 1 year) of CsA, as may be required in atopic dermatitis, is limited by risk of side‐effects, although off‐label use beyond 1 year has been reported . Side‐effects associated with CsA include hypertension, nephrotoxicity and subjective side‐effects (e.g.…”

Basal Serum Cortisol and Adrenocorticotropic Hormone Levels in Patients with Atopic Dermatitis

“…Basal serum cortisol level was found to be higher than the reference range in one patient from the AD group (3.2%); however, none of the Topical corticosteroids are the most widely used and the mainstay of treatment for AD [12], but there is increasing concern about their systemic side effects, especially adrenal suppression. There is some evidence that the percutaneous systemic absorption of topical steroids may occur after the prolonged use of these drugs and may lead to the suppression of hypothalamic-pituitary-adrenal axis (HPAA) [13,14]; however, in the majority of these studies, "basic" HPAA function (before application of topical steroids) remained unevaluated. In other words, in most of these studies, the HPAA function was compared with controls only "after" the application of topical steroids.…”

The role of phosphodiesterase 4 in the pathophysiology of atopic dermatitis and the perspective for its inhibition

“…Other topical PDE4 inhibitors that have been or that are currently in development for treatment of AD include E6005/RVT‐501, LEO 29102, OPA‐15406/MM36 and DRM02 . Unlike crisaborole, none of these investigational drugs contains boron; however, like crisaborole, they generally fall under the 500‐Dalton rule in terms of molecular weight, allowing for skin penetration (Figure ) .…”