Atopic dermatitis: a review of evolving targeted therapies

ABSTRACT

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin condition, affecting a significant number of patients of all ages. As we learn more about the pathogenesis of AD, new targeted treatment options are being developed to better tailor its management. Currently, a variety of biologic agents are utilized to target specific components and regulators of the inflammatory pathways in allergic and inflammatory conditions. These targeted therapies allow for greater efficacy while limiting adverse effects.

Areas covered: This review examines the current literature in respect to several different monoclonal antibodies that are being studied toward a personalized approach in the treatment of AD.

Expert opinion: Several trials examining the use of biologics for AD have demonstrated mixed success. While some have shown promise for improvement of clinical symptoms, there are several barriers to support consistent use including cost, adverse effects, small sample sizes, conflicting evidence, and lack of demonstrated long-term safety and efficacy. The ultimate goal for future research is to develop biomarkers for different AD phenotypes in order to allow for targeted therapy of AD.

KEYWORDS:

• Atopic dermatitis
• biologics
• cytokines
• eczema
• immunomodulators
• interleukin
• monoclonal antibodies

Article highlights

• Atopic dermatitis is the most common chronic inflammatory skin disease.

• The predominant cytokines involved in the pathogenesis of AD are IL-4 and IL-13.

• There are numerous and varied treatment options and guidelines for AD amongst dermatologists and allergists.

• Dupilumab, an anti-IL-4Rα mAb, is the only FDA approved immunomodulator affecting the Th2 pathway.

• Other Th2 pathway targeted mAbs, including tralokinumab and lebrikizumab, have also shown promise in treating AD and further studies are underway.

• Though in a small trial, the failure of mepolizumab, an IL-5 monoclonal antibody, to show benefit in treating atopic dermatitis may suggest that IL-5 and eosinophils play less of a role in AD than once previously thought.

• Anti-IL-31 mAbs, thought to play a role in transmission of pruritus, have shown benefit in the treatment of moderate-to-severe AD; however, the trial was limited by small sample size.

• Tezepelumab, an anti-TSLP mAb, has shown some benefit in AD, but failed to reach the primary endpoint of improvement of EASI-50.

• Several mAbs such as omalizumab, rituximab, ustekinumab, and secukinumab have had conflicting results in AD treatment, mostly because literature is limited to case reports and studies with a small sample size.

• Despite showing promise in small trials, the T cell inhibitors efalizumab and alefacept have been withdrawn from the market in Europe and the US due to cases of progressive multifocal leukoencephalopathy and cost of production, respectively.

• In a small study fezakinumab, an IL-22 monoclonal antibody, showed improvement in the treatment of severe AD by altering epidermal hyperplasia.

• TNF-alpha inhibitors such as infliximab and etanercept have demonstrated mixed results in small clinical trials; with some reports of AD exacerbation in patients taking infliximab.

• The topical JAK-kinase inhibitor tofacitinib improved AD in a phase II trial while the oral form, baricitinib is still under study.

• Several targeted anti-pruritic agents such as tradipitant, aprepitant, serlopitant, asimdoline, and rosiglitazone are also currently being studied.

• There are numerous new medications being developed for atopic dermatitis, however very few have been studied extensively enough to show clear benefit for or against their use.

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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

A reviewer on this manuscript has disclosed that they have received research, speaking and/or consulting support from a variety of companies including Galderma, GSK/Stiefel, Almirall, Leo Pharma, Boehringer Ingelheim, Mylan, Celgene, Pfizer, Ortho Dermatology, Abbvie, Samsung, Janssen, Lilly, Menlo, Merck, Novartis, Regeneron, Sanofi, Novan, Qurient, National Biological Corporation, Caremark, Advance Medical, Sun Pharma, Suncare Research, Informa, UpToDate and National Psoriasis Foundation. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose

Additional information

Funding

This paper was not funded.