Cyclosporine is still the gold standard for treating atopic dermatitis in adults requiring systemic treatment. It is, however, supported by a growing number of molecules. First, we have dupilumab and tralokinumab, which target the alpha subunit of the interleukin (IL)-4 receptor common to IL-13, and IL-13, respectively. Then, we have the Janus kinase (JAK) inhibitors baricitinib, upadacitinib, and abrocitinib.
In children, the molecules accessible as first-line treatment depend on the age limit assigned to their marketing authorization. Dupilumab is approved for patients from 6 months of age, baricitinib for patients from 2 years of age, and tralokinumab and upadacitinib for children aged 12 years and over. Delphine Staumont-Sallé, MD, PhD, a dermatologist at Claude-Huriez Hospital and Lille Regional University Hospital in France, spoke during the dermatology conference held in Paris in December 2023. She emphasized that innovation in the field of atopic dermatitis is ongoing, with numerous molecules currently under investigation, several of which work via new mechanisms of action.
On the Starting Blocks
Among the already well-defined mechanisms, the next molecule to be registered could be lebrikizumab. It blocks the alpha 1 receptor of IL-13 but not the alpha 2 receptor. It's thought that this property gives it a regulatory effect favorable to its efficacy. According to data from phase 3 trials conducted in adults and adolescents, its efficacy after 52 weeks and its tolerability profile are favorable.
As for nemolizumab, this monoclonal antibody targets the mechanism linked to IL-31, which has an important role as a mediator of pruritus. In atopic dermatitis, scratching promotes a chronic itch-and-scratch cycle that prevents healing of the skin barrier. Data from clinical studies conducted in adolescents and adults show a clear benefit of the IL-31RA receptor-targeting nemolizumab in terms of healing and, in particular, the Investigator Global Assessment score, with a good tolerability profile.
"JAK inhibitors are also starting to be used to treat atopic dermatitis in adults and adolescents. Topical applications could be of benefit in treating moderate to severe types that are not very widespread, as an alternative in patients not responsive to topical corticosteroids or topical calcineurin inhibitors, thereby avoiding the use of systemic treatments," said Staumont-Sallé.
Upcoming Drug Groups
Other molecules have more preliminary data. Two of them, rocatinlimab and amlitelimab, are antibodies acting upstream: The former binds to OX40-activated T-cells, whereas the latter binds to the OX40L ligand on the antigen-presenting cell. Both inhibit interaction between the two cells. "By acting upstream, this approach doesn't just block Th2 cells, which could help certain patients with mixed endotype," said Staumont-Sallé. "What's more, it should also help keep patients in remission." This point will have to be determined via phase 3 studies. For now, phase 2b studies are encouraging: For example, 68% of patients achieved efficacy at 12 weeks after a final injection of rocatinlimab and maintained it for an additional 24 weeks.
Temtokibart is an IL-22 inhibitor. "This IL plays an important role in hyperplasia," explained Staumont-Sallé. "Consequently, this treatment has been studied for use in treating older cases of severe atopic dermatitis with high levels of lichenification." The initial phase 2 results show that 20% of patients achieve full remission after 4 months.
Finally, tapinarof is an aryl hydrocarbon receptor agonist that plays an important role in skin homeostasis. It regulates innate and adaptive immune responses, as well as Th17 cells and regulatory T cells. A topical form of the drug is already on the market in the United States to treat psoriasis. Its use in treating atopic dermatitis in children over the age of 2 years and adults has been studied as part of phase 3 studies. For now, it's tolerability profile looks good.
This article was translated from Univadis France, which is part of the Medscape Professional Network.