Current and emerging biologic and small molecule therapies for atopic dermatitis

ABSTRACT

Introduction: Atopic dermatitis (AD) is the most common inflammatory skin disease, yet until recently there were no safe systemic therapies approved for the long-term management of AD in adult patients. A deeper understanding of disease pathogenesis and identification of molecular and cellular changes has resulted in a rapidly evolving pipeline of therapeutics that holds promise for safer long-term control.

Areas covered: In this review, we highlight the growing arsenal of biologic and small molecule antagonists that target pathways implicated in AD pathogenesis. Evidence that AD is driven by multiple immune axes extending beyond the Th2 polarization has resulted in therapies targeting additional pathways, including the Th22, Th17/IL-23, and JAK-STAT pathways. Pruritus, a hallmark of AD, has been linked to multiple mechanisms and various therapeutics have emerged in response to alternative hypotheses.

Expert opinion: Despite the assumption that AD has a common disease mechanism, recent studies indicate that the disorder is characterized by several phenotypes and therapy may need to be tailored to the unique immune traits of specific phenotypes. Targeted therapy should complement and expand our molecular map of AD across the various phenotypic iterations and help push AD pharmacotherapy into a new era of personalized medicine.

KEYWORDS:

• Atopic dermatitis
• eczema
• therapeutics
• biologics
• monoclonal antibody
• small molecule
• targeted treatment

Article highlights

• The success of immune pathway mapping in the treatment of psoriasis and the approval of dupilumab, the first biologic treatment for AD, have set the stage for a revolution in AD pharmacotherapy.

• Although traditionally considered a Th2 polarized skin disease, the increasing recognition of contributions from Th22, Th17/IL-23, and Th1 pathways have resulted in many exciting, targeted therapeutics that have reached phase II and III status and have shown encouraging early results.

• Addressing pruritus, a hallmark of AD, continues to be a priority in AD treatment and has led to the development of several promising therapeutics with disparate strategies, including a KOR agonist and antagonists of IL-31, NK-1R, and H4R.

• Success in clinical trials has commensurately contributed to a rapidly evolving understanding of the pathogenesis of AD and the emergence of a new paradigm of AD that has revealed the disorder to be a set of heterogeneous phenotypes.

Unique contributions from immunologic pathways underlying specific AD phenotypes may justify the use of targeted therapies tailored to individuals.

Declaration of interest

E Guttman-Yassky is an employee of Mount Sinai and has received research funds (grants paid to the institution) from: Abbvie, Celgene, Eli Lilly, Janssen, Medimmune/Astra Zeneca, Novartis, Pfizer, Regeneron, Vitae, Glenmark, Galderma, Asana, Innovaderm, Dermira, UCB. E Guttman-Yassky is also a consultant for Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor, AnaptysBio, Dermira, Galderma, Glenmark, Novartis, Pfizer, Vitae, Leo Pharma, Abbvie, Eli Lilly, Kyowa, Mitsubishi Tanabe, Asana Biosciences, and Promius. The authors have no other 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 apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.