The evolving landscape of biologic therapies for atopic dermatitis: Present and future perspective

Abstract

Atopic dermatitis (AD) is one of the most common, chronic inflammatory skin diseases. The Global Burden of Disease study showed that approximately 15%-20% of children and up to 10% of adults suffer from AD with prevalence also varying among races and ethnicities. [1][2][3][4] AD belongs to a family of atopic disorders, including food allergy, asthma and allergic rhino-conjunctivitis, which are often comorbid. 5,6 The clinical presentation of AD is highly heterogeneous, influenced by age of onset, disease stage, chronicity, severity, ethnicity and geographical location, with pruritus and eczematous lesions common to all subtypes. 7-9 AD is characterized as an immune-mediated disorder, with corresponding impaired skin barrier function. [10][11][12][13][14][15][16] Th2 immune axis dysregulation is considered central to AD pathogenesis. 17,18 More recently, the understanding of the complex inflammatory processes underlying disease pathogenesis has significantly expanded, challenging the monolithic disease model of AD. Phenotypic differences across patient types have been better elucidated by unique biomarker findings. 19 Comparisons based on age show differing contributions from Th2/Th22 and Th1/Th17 biomarkers, [20][21][22] with differing immune phenotypes also among Asians and African Americans with AD. [23][24][25][26][27] The continuously expanding understanding of AD pathogenesis underlies the rapidly evolving landscape of new therapeutic approaches, among which are biologic therapies (Figure 1). Through

Targeting SERCA2 in organotypic epidermis reveals MEK inhibition as a therapeutic strategy for Darier disease

“…The advent of rational molecular therapeutics has revolutionized the treatment of many dermatologic conditions (4, 5); however, most advances have been made for common inflammatory diseases, like psoriasis and atopic dermatitis, driven by soluble cytokines amenable to targeting by monoclonal antibodies (72, 73). Unfortunately, skin blistering diseases and disorders of cornification are rare and most lack any FDA-approved treatments, though recent work suggests cytokine targeting may improve certain subtypes of ichthyosis (74–76).…”

CLA+ memory T cells in atopic dermatitis

“…AD is characterized by a compromised skin barrier, abnormal cutaneous immune responses, altered microbiota, and intense pruritus. Translational knowledge derived from the efficacy and mechanism of targeted therapies in AD patients has allowed identifying key disease pathways, such as Th2‐derived cytokines IL‐13, IL‐4 and IL‐31 and IL‐22 61–63 . The majority of infiltrating cells in AD lesional skin are CD3 + CD4 + CD45RO + CLA + T cells, 30,64 which are related to different aspects of AD, including clinical features, response to treatment, and biomarkers (Figure 1).…”

“…and IL-22. [61][62][63] The majority of infiltrating cells in AD lesional skin are 30,64 which are related to different aspects of AD, including clinical features, response to treatment, and biomarkers (Figure 1).…”

Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells

“…Atopic dermatitis (AD), the most common chronic inflammatory skin disease, has long been a therapeutic challenge, especially in its moderate-to-severe form 1 . Due to the recent advent of novel targeted therapeutics, treatment options for these patients have improved considerably 2 – 4 . The success of these agents not only contributed to the unraveling of many cellular and molecular mechanisms relevant to AD pathogenesis, but also resulted in an increased overall understanding of skin immunobiology 1 , 5 – 11 .…”