New and Emerging Systemic Treatments for Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a prevalent inflammatory skin condition that, depending on its severity, can cause enormous morbidity. Corticosteroids and systemic immunosuppression, traditionally standard of care for difficult-to-treat disease, have many undesirable side effects. The desire for targeted treatments along with an improved understanding of the pathophysiology of AD has spurred the development of novel treatments. In this article, we review promising new treatments and discuss how their targets-IL-13, IL-31, OX40 (CD134), and the Janus kinase family of proteins-participate in the pathogenesis of AD. We review the published phase II and III data for dupilumab, tralokinumab, lebrikizumab, nemolizumab, anti-OX40 antibody, baricitinib, abrocitinib, and upadacitinib. The introduction of new agents may offer new options, but it remains to be seen how narrow-acting agents, like single interleukin inhibitors, will compare in safety and efficacy to broad-acting agents such as JAK inhibitors. Key Points Our better understanding of the pathophysiology of AD has resulted in an explosion of research into new immunotherapies for this patient population. Multiple new agents targeting IL-13, IL-31, OX40 (CD134), and Janus kinase proteins may be effective for AD.

Interleukin-31 and Pruritic Skin

“…However, chronic pruritus that lasts more than 6 weeks is highly problematic because it markedly deteriorates quality of life, mental health and sleep quality in the afflicted individuals [ 1 , 2 , 3 , 4 , 5 ]. Chronic pruritus is the major symptom in many inflammatory skin diseases such as atopic dermatitis, prurigo nodularis, eczema, chronic urticaria and psoriasis [ 1 , 2 , 3 , 4 ]. Scratching clearly exacerbates the predisposing dermatitis, which may further enhance pruritus and result in an itch/scratch vicious cycle [ 6 ].…”

“…Recent studies have revealed numerous itch-inducing factors or pruritogens [ 1 , 2 , 3 , 4 , 7 , 8 ]. Specific receptors for these pruritogens are expressed on cutaneous sensory nerve fibers, which are mostly small C-fibers innervating the epidermis and dermis [ 9 ].…”

Chrysin Inhibits TNFα-Induced TSLP Expression through Downregulation of EGR1 Expression in Keratinocytes

“…Topical therapy includes the application of corticosteroids, antihistamine, and immunosuppressants (e.g., calcineurin inhibitors and phosphodiesterase inhibitors) [ 5 ]. Systemic administration comprises immunosuppressant-modulators (e.g., cyclosporine), anti-metabolites (e.g., methotrexate and azathioprine), cytokine signaling inhibitor (e.g., JAK kinase inhibitor), antibiotics, and biological agents (e.g., targeted monoclonal antibodies) [ 6 , 7 , 8 , 9 ]. Topical steroids and immunosuppressants have been used as the primary agents; however, their value is limited by local side effects and insufficient efficacy [ 10 ].…”

Atopic Dermatitis as a Multifactorial Skin Disorder. Can the Analysis of Pathophysiological Targets Represent the Winning Therapeutic Strategy?

“…In this case, the new treatment options with antibodies (Ab), especially with the Ab Dupilumab, against interleukin-4 receptor revealed great potential without serious side effects [ 35 , 36 , 37 , 38 ]…”