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New treatments for atopic dermatitis

In a recent article, researchers discussed current atopic dermatitis treatments, along with the need for safe and effective long-term treatments.

More long-term treatments for atopic dermatitis (AD) must be developed, according to investigators.

AD affects over 16 million adults and 9 million children in the United States, often persisting into adulthood. Treatments such as topical corticosteroids (TCSs) can cause localized skin atrophy, telangiectasia, striae, perioral dermatitis, and acne, with further adverse events from extensive use.

Multiple short-term treatment options have been or are being developed for AD, such as:

JAK inhibitors

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway is responsible for inflammation and itching of the skin. JAK inhibitors target JAK receptors to inhibit this process. Two notable JAKs were discussed by investigators.

One JAK inhibitor treatment includes topical ruxolitinib cream (Opzelura; Incyte), approved by the US Food and Drug Administration (FDA) in September 2021 for short-term AD. In multiple studies, ruxolitinib successfully reduced itching in patients aged 12 years and above with AD, with nasopharyngitis being the most reported adverse event.

Another upcoming JAK inhibitor is delgocitinib (Corectim; LEO Pharma), an ointment used in Japan to treat children and adults with AD. Recently, a cream has begun development, and a phase 3 study took place in May 2021 for patients aged over 18 years. Currently, neither product is approved for use in the United States.

Topical calcineurin inhibitors (TCIs)

Tacrolimus and pimecrolimus are two TCIs approved in the early 2000s. These products are often used in patients after TCSs fail and can be used short-term or intermediately. They inhibit T cell activation to prevent inflammation, without risk of skin atrophy. However, they can cause skin burning and irritation.

Tacrolimus 0.03% ointments can be used against moderate-to-severe AD in children aged 2 to 15 years, with 0.1% ointments only being approved for adult use. Pimecrolimus 1% cream (Elidel; Novartis) can be used in adults and children aged 2 years and above to treat mild-to-moderate AD.

PDE4 inhibitors

Phosphodiesterase-4 (PDE4) inhibitors have also been developed to mediate inflammation. Rofumilast cream (Daliresp; Arcutis), used to treat plaque psoriasis, is currently being studied for AD use. A phase 3 trial began for 0.15% cream in February 2021, and 0.3% cream is approved for psoriasis in the United States for patients aged 12 years and older. Pediatric use of a 0.05% cream entered a phase 3 trial in April 2021.

Difamilast ointment (Moizerto; Otsuka) has also been approved in Japan for individuals aged 2 years and above. It is currently not approved in the United States.

Additionally, crisaborole 2% ointment (Eucrisa; Pfizer) was approved for use in the United States for patients aged 2 years and above in 2016. This approval extended to children aged as young as 3 months in 2020.

Other interventions in development

There are further products in development for treating AD, such as tapinarof (GSK2894512 cream, WBI-1001, or Benvitimod; Shenzhen). A phase 3 trial of tapinarof for treatment of AD began in August 2021, and the product is currently approved for psoriasis in adults.

Microbial interventions such as Forte B-401 and Staphylococcus hominis A9 have also undergone tests for AD, but the phase 2 trial for Forte B-401 failed to meet statistical significance. Multiple targeted agents are also undergoing clinical trials, most of which are in phase 1 or phase 2 trials.

These treatments are just some of the available or upcoming medicines for AD. As AD is often lifelong, investigators stressed that long-term treatments with minimal adverse events (AEs) are the most valuable for patients suffering from AD.

“The aim of developing targeted therapy for AD is to provide control of inflammation and pruritus with improvement of barrier function while minimizing AEs.” wrote the authors. “By elucidating the complex pathogenesis of AD, additional targets for therapy can be developed. Many patients with AD require lifelong treatment. Thus, there is an unmet need for topical therapies with high efficacy and low risk of AEs with long-term use.”

Reference

Kleinman E, Laborada J, Metterle L, et al. What’s New in Topicals for Atopic Dermatitis?. Am J Clin Dermatol 23, 595–603 (2022). https://doi.org/10.1007/s40257-022-00712-0