Targeting aryl hydrocarbon receptor represents novel approach to atopic dermatitis therapy
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Key takeaways:
- Changes in the aryl hydrocarbon receptor (AhR) are associated with atopic dermatitis.
- The efficacy of tapinarof, an AhR agonist, validates the targeting of AhR as a novel approach.
The efficacy of tapinarof cream 1% has validated the aryl hydrocarbon receptor as a therapeutic target for the treatment of atopic dermatitis, according to a study.
“[The aryl hydrocarbon receptor (Ahr)] is expressed ubiquitously through the body, has roles in many physiologic processes and is activated by a wide range of ligands,” Lawrence F. Eichenfield, MD, FAAD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego and a member of Healio’s Dermatology Peer Perspective Board, and colleagues wrote. “AhR also affects signaling through interaction with other proteins, such as the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2).”
AD is associated with changes in AhR signaling and reduced Nrf2 activity which has led researchers to believe that using therapies that target AhR may improve disease.
In this review, the authors discussed the rationale for targeting AhR in the treatment of AD based on the current understanding of the role of tapinarof cream 1% in the treatment of inflammatory skin disease.
Tapinarof is a nonsteroidal AhR agonist that is approved by the FDA for the treatment of plaque psoriasis in adults and is under investigation for the treatment of psoriasis and AD in children aged as young as 2 years and AD in adults.
In two identical, 12-week, pivotal phase 3 trials, tapinarof demonstrated significant efficacy vs. vehicle and was well tolerated in adults with mild to severe plaque psoriasis. Additionally, in the ADORING phase 3 program, the drug performed well for the treatment of AD.
According to the authors, the efficacy of tapinarof can be attributed to its specific binding and activation of AhR. This presents many benefits to patients with AD.
First, targeting AhR results in the downregulation of pro-inflammatory cytokines that are implicated in the pathogenesis of AD. Activating AhR also normalizes the skin-barrier function by increasing the expression of skin-barrier proteins such as filaggrin, loricrin, hornerin and involucrin. Lastly, tapinarof’s mechanism of action increases antioxidant responses by activating Nrf2.
“Clinical trials with tapinarof ... validate AhR as a therapeutic target for the treatment of inflammatory skin diseases,” the authors said. “The targeting of transcription factors such as AhR represents a novel approach to AD therapy, distinct from treatments that target specific cytokines and enzymes.”
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