ATOPIC DERMATITIS

Atopic dermatitis (AD), also referred to as atopic eczema is a complex, chronic relapsing skin disease characterized by underlying type 2 inflammation often occurring in families with atopic diseases (AD, food allergy, bronchial asthma or allergic rhinoconjunctivitis) with recent evidence suggesting it is a systemic disease. With a prevalence of 4% in young adults and up to 15% in children, AD is one of the most common skin diseases. Moderate-to-severe AD is highly symptomatic and can have a profound multidimensional burden on patients.

Frequent, intense pruritus and sleep loss are the most recognized and impactful symptoms contributing to reduced quality of life and worse psychological and overall health status among patients.

Treatment options are still limited for adults and children with moderate-to-severe AD uncontrolled with currently approved topical and/or systemic treatments. Long-term use of systemic immunosuppressants as cyclosporine A (the only approved drug in France until 2019) is not recommended due to unfavorable benefit-risk profiles. Despite AD prevalence and high burden, use of systemic immunomodulators to treat AD is still surprisingly low in moderate-to - severe patients.

Dupilumab, an IIL‐4Rα‐blocker, was the first approved biologic in France for patients with type 2 inflammatory diseases, including AD, asthma, and chronic rhinosinusitis with nasal polyps. Since september 2022, Tralokinumab, Interleukin 13 inhibitor (IL 13) is also on the market.

AD remains a complex disease involving multiple combinatorial factors and is characterized by heterogenous clinical patterns. There is therefore a need to better define these different clinical phenotypes to improve the management of the disease and start the right treatment for each patient.

Many other biologics and/or small molecules, which interfere with different cytokines and signalling pathways, are currently being tested in phase II and III trials, for example Fezakinumab (anti-IL-22), Etokimab (anti-IL-33), Nemolizumab (anti-IL-31Rα) and Tezepelumab (anti-TSLP). Other biologics targeting key pathways of the atopic immune response, as well as various janus kinase (JAK) inhibitors, are among the emerging therapeutic options. Baricitinib was the first JAK inhibitor authorised in France in 2021. Upadacitinib was approved in August 2021 and Abrocitinib has been approved since March 2022, and other JAK inhibitors are likely to become available in the next two years in this indication in France.

The simultaneous emergence of many new topical and systemic drugs for the treatment of AD in clinical trials, and the perspective for some licensed systemic drugs even for childhood AD in the near future will considerably change the field of AD management. Future studies will lead to better phenotyping the patients and identify biomarkers in order to stratify patients’ management. While there is some evidence on the short‐term effectiveness of these treatments, there is a clear lack of head‐to‐head comparison trials and a paucity of data on the long‐term effectiveness and safety of such treatments.