Testing biologics and intracellular signaling inhibitors on pediatric atopic dermatitis: a stairway to modern therapeutic approaches

ABSTRACT

Introduction: Atopic dermatitis (AD) is the most common cutaneous inflammatory disease in adults and children. In the last few years, the pathogenesis of AD has been profoundly revised, and this has led to the identification of novel druggable targets and the development of new agents targeting specific molecular pathways. Despite the high prevalence of AD in the pediatric population, the clinical development of new treatments, either topical or systemic, has been focused on the adult population in recent years; only a limited number of these new agents have been tested in pediatric cohorts.

Areas covered: In this review, we describe the pathogenic model of pediatric AD which shows similarities and substantial differences when compared to adult AD. The identification of therapeutic targets is highlighted, and novel targeted therapies, both topical and systemic, are discussed.

Expert opinion: The current therapeutic armamentarium for pediatric AD is very limited, and this represents a critical unmet need. The enhancement of clinical research on pediatric patients is necessary to facilitate an increase in the number of new targeted therapeutic options being available on the market.

KEYWORDS:

• Pediatric atopic dermatitis
• targeted drugs
• biologic
• PDE4 inhibitor
• JAK inhibitor

Article highlights

• The immunologic profile is characterized by a marked enhancement of Th2 signaling, associated with the upregulation of Th22, Th17, and Th1 pathways.

• Despite strong Th2 induction, both pediatric lesional and nonlesional AD clustered around psoriasis but not adult AD, demonstrating substantial differences related to the gene expression profile and immune pathway activation.

• These differences between pediatric and adult AD could also have important implications from the therapeutic point of view bringing distinct treatment approaches for children.

• New agents in pipeline for pediatric AD entered the clinical phase, and they include PDE4 inhibitors, JAK inhibitors, LXR agonist, 5-lipoxygenase inhibitor, phospholipase A2 inhibitor, transient receptor potential vanilloid type 1 (TRPV1) channel inhibitor, aryl hydrocarbon receptor (AhR) agonist, IL-4Rα receptor subunit antagonist, selective IL-13 blocker, IgE blocker, and IL-1R antagonist.

• A limited number of head-to-head studies and trials in pediatric AD patients have been proposed, and this represents an unmet need that needs to be addressed.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One peer reviewer is a Consultant for Regeneron Pharmaceuticals. Other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.