Interleukin antagonists for atopic dermatitis: a new era of therapy

ABSTRACT

Introduction

Over the last decade, increasing understanding of the immunopathogenesis of atopic dermatitis (AD) enabled the recognition of multiple therapeutic targets and subsequently the development of novel, highly effective systemic treatments, including interleukin (IL)-antagonists. To date, the IL-4Ra-inhibitor dupilumab, and the IL-13 inhibitor tralokinumab, have gained regulatory approval in Europe for the treatment of moderate-to-severe AD, while more than 70 new therapeutics are currently in development.

Areas covered

In this review, we address the role of ILs in the pathogenesis of AD and provide an overview of the novel and investigational IL-antagonists, as regards their efficacy and safety on moderate-to-severe AD.

Expert opinion

Current data have established IL-4 and IL-13 inhibitors as effective and safe for the treatment of moderate-to-severe AD, as regards the rapid control of flares as well as the long-term remission of the disease. Data regarding the efficacy and safety of other IL-inhibitors, including those targeting IL-31, IL-22, IL-33, IL-36 and IL-18, are accumulating. There is still an unmet need for real-world-evidence studies and head-to-head studies for both currently available and future agents in AD treatment. Establishing predictive biomarkers of treatment response in a disorder of such considerable heterogenicity might help physicians pursue a patient-tailored therapeutic response.

KEYWORDS:

• Atopic dermatitis
• interleukin inhibitors
• treatment
• Th2 immune response
• dupilumab
• tralokinumab
• lebrikizumab
• nemolizumab

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Article highlights

• Interleukin (IL)-4 and IL-13 inhibitors have been proven to be effective and safe for the treatment of moderate-to-severe atopic dermatitis (AD), as regards the rapid control of flares as well as the long-term remission of the disease

• Among the novel and investigational IL-inhibitors, dupilumab, tralokinumab, lebrikizumab and nemolizumab constitute the biological agents with the most robust evidence on efficacy and long-term safety

• Biological agents targeting other ILs, which are implicated in pathogenesis of AD, including IL-31, IL-22, IL-33, IL-36 and IL-18 are currently under investigation in phase II and III studies

• There is an unmet need of real-world-evidence studies and head-to-head studies both for currently available and future agents for the treatment of AD

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

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

IL, interleukin; US, United States

Additional information

Funding

This paper was not funded.