Cyclosporine is still considered the gold standard for treating atopic dermatitis in adults requiring systemic treatment. However, it is being supported by a growing number of molecules. First, we have Dupilumab and Tralokinumab which target the alpha subunit of the interleukin (IL)-4 receptor, which is common to IL-13. Then, we have the Janus kinase (JAK) inhibitors Baricitinib, Upadacitinib, and Abrocitinib.
The availability of these molecules for initial treatment in children depends on the age limit for their market approval. Dupilumab is approved for patients over 6 months, Baricitinib for patients over 2 years, and Tralokinumab and Upadacitinib for children over 12 years. Dr. Delphine Staumont-Sallé, a dermatologist at the Claude Huriez Hospital and the Regional University Hospital of Lille in France, emphasized during the dermatology conference in Paris in December 2023 that innovation in the field of atopic dermatitis is ongoing, with numerous molecules being investigated, some of which act through new mechanisms of action.
Among the already clearly defined mechanisms, Lebrikizumab could be the next molecule to be registered. It blocks the IL-13 alpha-1 receptor but not the alpha-2 receptor, which is believed to give it a regulatory effect that enhances its efficacy. Data from Phase-3 studies in adults and adolescents show favorable efficacy and safety profiles after 52 weeks.
As for Nemolizumab, this monoclonal antibody targets the mechanism associated with IL-31, which plays an important role as a mediator of pruritus. Scratching in atopic dermatitis promotes a chronic itch-scratch cycle that prevents the healing of the skin barrier. Data from clinical studies in adolescents and adults show a clear benefit of Nemolizumab targeting the IL-31RA receptor in terms of healing and particularly the Investigator Global Assessment Scores, with a good safety profile.
„JAK inhibitors are also increasingly being used to treat atopic dermatitis in adults and adolescents. Topical applications could be beneficial for the treatment of moderate to severe forms, which are not very common, as an alternative for patients who do not respond to topical corticosteroids or topical calcineurin inhibitors, thus avoiding the use of systemic treatments,“ said Staumont-Sallé.
Future Drug Classes
For other molecules, preliminary data is available. Two of them, Rocatinlimab and Amlitelimab, are upstream antibodies: the former binds to OX40-activated T cells, while the latter binds to the OX40L ligands of the antigen-presenting cell. Both inhibit the interaction between the two cells. „This approach not only blocks Th2 cells, which could help certain patients with a mixed endotype,“ said Staumont-Sallé, „but it also aims to help patients remain in remission.“ This point needs to be determined through Phase-3 studies. Currently, the Phase 2b studies are encouraging, with, for example, 68% of patients maintaining efficacy 12 weeks after the last injection of Rocatinlimab for an additional 24 weeks.
Temtokibart is an IL-22 inhibitor. „This IL plays an important role in hyperplasia,“ explained Staumont-Sallé. „For this reason, this treatment has been investigated for the treatment of older cases of severe atopic dermatitis with a high degree of lichenification.“ The initial results of the Phase 2 show that 20% of patients achieve complete remission after 4 months.
Finally, Tapinarof is an aryl hydrocarbon receptor agonist, which plays an important role in skin homeostasis. It regulates innate and adaptive immune responses as well as Th17 cells and regulatory T cells. In the US, a topical form of the drug is already on the market for the treatment of psoriasis. Its use for the treatment of atopic dermatitis in children over 2 years and adults has been investigated in Phase-3 studies. At the moment, the safety profile looks good.
This article was translated by Univadis France, which is part of the Medscape Professional Network.