Shedding light on key pharmacological knowledge and strategies for pediatric atopic dermatitis

ABSTRACT

Introduction

Atopic dermatitis (AD) is an inflammatory disease affecting over 20% of the pediatric population, with 85% of cases presenting before the age of five. Recently, therapeutic options in pediatric patients have evolved rapidly, following extensive development in adult treatments.

Areas covered

This review will encompass relevant molecular drivers, along with an overlook on treatment modalities in pediatric AD, as well as a summary of pipeline treatments in clinical trials for pediatric patients from PubMed, Google Scholar, and Clinicaltrials.gov up to July 2022. Topical corticosteroids are the mainstay for AD flares in adults and children. Topical approved agents in pediatric AD are calcineurin inhibitors, crisaborolecrisaborole, and ruxolitinib. Dupilumab is the only FDA approved biologic for patients with AD from six months of age. A Janus kinase inhibitor, upadacitinib, is a systemic treatment approved for pediatric AD patients (age >12 years). Systemic immunosuppressants used in pediatric AD include methotrexate, azathioprine, cyclosporinecyclosporine, and mycophenolate mofetil.

Expert opinion

Data regarding disease prevention are conflicting, however, an abundance of research has transpired regarding amelioration of symptoms and induction of disease clearance by targeting numerous pathological mechanisms. Understanding the pediatric AD phenotype will further advance the field and the development of improved therapeutics.

KEYWORDS:

• Atopic dermatitis
• eczema
• pediatric
• topical corticosteroids
• calcineurin inhibitors
• systemics
• methotrexate
• azathioprine
• mycophenolate mofetil
• crisaborole
• dupilumab
• janus kinase inhibitor

Article highlights

• There are clinical differences seen between pediatric and adult atopic dermatitis (AD) (including, for example, more skin infections in younger patients and extensor vs flexural lesional distribution in pediatric and adult AD, respectively), and recent studies have suggested differences in molecular characteristics of AD in pediatric and adult patients.

• It is currently still unclear whether AD and atopic march prevention are feasible with available therapeutics.

• TCS, TCI, CrisaboroleCrisaborole, and systemic immunosuppressants have demonstrated promising results, however each is associated with its own unique risk.

• Dupilumab is the first biologic approved for pediatric AD patients as young as 6 months old.

• Upadacitinib is the first systemic JAK inhibitor to be approved for pediatric AD patients >12 years.

• The FDA recently granted lebrikizumab Fast Track designation for moderate-to-severe AD in adult and adolescent patients (12-1812–18 and >40 kg), making it the second biologic agent approved for AD in adolescents.

Declaration of interests

E Guttman-Yassky has served as a consultant for AbbVie, Amgen, Allergan, Asana Bioscience, Celgene, Concert, Dermira, DS Bio- pharma, Escalier, Galderma, Glenmark, Kyowa Kirin, LEO Pharmaceuticals, Lilly, Mit- subishi Tanabe, Novartis, Pfizer, Regeneron, Sanofi, and Union Therapeutics; is a member of advisory boards for Allergan, Asana Bioscience, Celgene, DBV, Dermavant, Dermira, Escalier, Galderma, Glenmark, Kyowa Kirin, LEO Pharma, Lilly, Novartis, Pfizer, Regeneron, and Sanofi; and is a recipient of research grants from AbbVie, AnaptysBio, AntibioTx, Asana Bioscience, Boehringer-Ingelheim, Celgene, DBV, Dermavant, DS Biopharma, Galderma, Glenmark, Innovaderm, Janssen Biotech, Kiniska Pharma, LEO Pharmaceuticals, Lilly, Medimmune, Sienna Biopharmaceuticals, Novan, Novartis, Ralexar, Regeneron, Pfizer, UCB, and Union Therapeutics. 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

A reviewer on this manuscript has disclosed research, speaking and/or consulting support from Eli Lilly and Company, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alovtech, vTv Therapeutics, Bristol-Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, Sun Pharma, Almirall, Galderma, Leo Pharma, Mylan, Celgene, Ortho Dermatology, Menlo, Merck & Co, Qurient, Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Teladoc, Eurofins, Informa, UpToDate and the National Psoriasis Foundation. They are also a founder and part owner of Causa Research and hold stock in Sensal Health. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was supported in part by the National Center for Advancing Translational Sciences, National Institutes of Health, through Rockefeller University to Y Renert-Yuval (grant # UL1TR001866).