New therapies for atopic dermatitis: Additional treatment classes

https://doi.org/10.1016/j.jaad.2017.12.024Get rights and content

Background

A wide array of miscellaneous agents is being studied for the treatment of atopic dermatitis (AD), including targeted topical, oral systemic, and biologic agents.

Objective

To review the known efficacy and safety to date for such agents being studied for the treatment of AD.

Methods

A nonsystematic review of the literature was performed. PubMed and ClinicalTrials.gov were searched for studies assessing agents not described previously for the treatment of AD. Randomized controlled trials were primarily sought, but other study types were also included if they contained pertinent data. Agents are presented by mechanism of action, with analysis of mechanism of action and data regarding efficacy and safety in patients with AD.

Results

Data regarding the following agents are presented: omiganan (an antimicrobial peptide), tapinarof (a nonsteroidal anti-inflammatory agent), PR022 (hypochlorous acid), asimadoline (a κ-opioid agonist), DS107 (dihomo-γ-linolenic acid), ZPL-389 (a histamine H4 receptor antagonist), secukinumab (an interleukin 17A inhibitor), and fezakinumab (interleukin 22 inhibitor).

Limitations

Limited clinical data exist for many of the described agents.

Conclusions

As recent research has improved our understanding of AD pathogenesis, various agents with unique mechanisms of action have been studied for the treatment of AD. Many of these hold great therapeutic promise for AD, and continued research and development is warranted.

Section snippets

AMP: omiganan

Antimicrobial peptides (AMPs) are short peptides within the innate immune system and are often potent antimicrobial agents. Although most AMPs have direct antimicrobial activity, others may modulate the host's innate immune system to promote pathogen clearance.9, 10 Patients with AD have decreased AMP production, resulting in microbial colonization, bacterial and viral infections, and possibly increased disease severity as measured via severity assessments (eg, SCORing Atopic Dermatitis

κ-Opioid agonists: asimadoline

Opioid receptors are hypothesized to be involved in cutaneous itch.39 It is believed that greater μ-opioid receptor activity compared with κ-opioid receptor activity results in pruritus.40 Preliminary data regarding the use of κ-opioid receptor agonists for pruritus indicate potential benefit. Nalfurafine, a κ-opioid receptor agonist, has been shown to significantly reduce refractory pruritus associated with end-stage renal disease,41, 42 and its use was approved for this indication in Japan in

IL 17A inhibitor: secukinumab

IL-17A, which is produced by T helper 17 cells, has been shown to be elevated in peripheral blood and lesions in patients with AD.76, 77, 78 IL-17A has also been found to stimulate T helper 2 responses in the acute phase of AD.79 However, the role of IL-17A in AD pathogenesis in unknown, although it might contribute to inflammatory responses in a subset of patients with AD.76 Secukinumab is a fully human monoclonal antibody directed against IL-17A that is currently US Food and Drug

Conclusion

As recent research and clinical trials have improved our understanding of AD pathogenesis, the landscape of AD pharmacotherapy is broadening and evolving at an unprecedented rate. A wide array of miscellaneous agents are in development for AD, including targeted topical, oral systemic, and biologic agents. Many of these agents hold great therapeutic promise, and continued research and development is necessary to continue to help shape AD pharmacotherapy.

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    Publication of this article was supported by Leo Pharma, Bayer, and Sanofi/Regeneron.

    Funding sources: Supported by Bayer, LEO Pharma, and Sanofi.

    Disclosure: Dr Silverberg has received honoraria for participation in advisory boards and/or consulting for Abbvie, Eli Lilly, Galderma, GlaxoSmithKline, Kiniksa, Leo, Menlo, Pfizer, Realm-1, Regeneron-Sanofi, and Roivant; performed contracted research from GlaxoSmithKline; and participated in a speaker's bureau for Regeneron-Sanofi. Dr Vakharia disclosed no conflicts of interest.

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