When topical therapy of atopic dermatitis fails: a guide for the clinician

ABSTRACT

Introduction

While topical medications are the first line of treatment for mild-to-moderate atopic dermatitis, they are ineffective in individuals with diffuse disease and moderate-to-severe atopic itch. For these individuals, as well as those who do not respond to topical treatments, systemic medicines are typically essential and helpful.

Areas Covered

We conducted a review of the literature to identify established systemic therapies, novel biologic agents, and recent advances in the pathophysiology of atopic dermatitis. The review discusses these data, which show that the majority of atopic itch medications now in development target the type 2 immune axis and brain sensitization, two main etiologies of atopic itch. We emphasize the evidence, efficacy, and side effect profiles of currently available systemic medications for atopic itch, as well as future potential for tailored therapy.

Expert Opinion

We give our professional opinion on the current state of knowledge about atopic eczema pathogenesis and the innovative targets and therapies for atopic itch that include MRGPRX2, periostin, gabaergic medicines, and JAK/STAT inhibitors. Additionally, we discuss patient populations that stand to benefit the most from targeting these molecules or utilizing these drugs, as well as those who may face a disproportionate weight of adverse effects.

KEYWORDS:

• Atopic dermatitis
• chronic pruritus
• dupilumab
• immunosuppressants
• neuronal treatment
• novel medications

Abbreviations

• AD: Atopic Dermatitis

• JAK: Janus Kinase

• MAb: Monoclonal Antibody

• PP-NRS: Peak Pruritus Numerical Rating Score (0–10)

• QD: Once per day

• QW: weekly

• Q2W: every other week

• SC: Subcutaneous

Article highlights

• Atopic dermatitis patients with moderate-to-severe itch or diffuse disease often require the use of systemic treatments

• Systemic treatment should begin with dupilumab

• For patients non-responsive to dupilumab or for those with acute flares, treatment with immunosuppressant medications, such as cyclosporine, may be warranted

• Neuronal medications, such as gabapentinoids, mirtazapine, or opioids, may prove effective for patients with severe nocturnal pruritus

• Significant medications on the horizon include oral janus kinase inhibitors, monoclonal antibodies targeted against IL-13, IL-31, and OX-40, and kappa opioid agonists

Declaration of interests

Gil Yosipovitch is a consultant for Pfizer, Galderma, Sanofi Regeneron, Kiniksa, Trevi, Eli Lilly, Novartis, GSK, Leo and Bellus, has received grant/research support from Leo Pharma, Pfizer, Novartis and Kiniksa, Sanofi Regeneron. 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

One of the peer reviewers in this manuscript works with the Contact Dermatitis Institute and with SmartPractice, a company that produces various dermatology supplies, including patch test products. Peer reviewers in this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.