How Do AHR Agonists Work?

Aryl hydrocarbon receptor (AHR) agonists are a novel class of drug approved by the FDA on May 25, 2022 for topical treatment of plaque psoriasis in adults. Currently, the first and only drug to be approved in this class is tapinarof, a steroid-free cream for topical application on the affected areas of the skin.

Plaque psoriasis is an inflammatory auto-immune condition, in which the immune system attacks the skin and causes the overgrowth of skin cells known as keratinocytes, resulting in plaques. Plaques are patches of silvery, flaky scales on the skin with red, inflamed, raised lesions that cause itching, burning and bleeding.

Aryl hydrocarbon receptors are transcription factors, protein molecules that are involved in the process of converting DNA into RNA, which carry the DNA instructions for cellular functions. Aryl hydrocarbon receptors are found in immune cells such as myeloid cells, innate lymphoid cells, B lymphocytes and certain subtypes of T cells.

Aryl hydrocarbon receptors, when activated, inhibit the release of proinflammatory proteins (cytokines) by immune cells and downregulate inflammation. AHR agonists work by binding to and activating aryl hydrocarbon receptors on the skin cells and immune cells that cause inflammation in plaque psoriasis.

The AHR agonist tapinarof is approved by the FDA for topical treatment of plaque psoriasis in adults. Tapinarof is a cream that is applied as a thin layer on the psoriasis-affected area once daily.

Side effects of AHR agonists may include the following:

• Inflammation of hair follicles in the skin (folliculitis)
• Inflammation of nose and throat (nasopharyngitis)
• Nasal congestion
• Nasal discharge (rhinorrhea)
• Sinus congestion
• Viral respiratory tract infection
• Contact dermatitis
• Hand dermatitis
• Rash
• Application site itching (pruritus)
• Generalized pruritus
• Genital pruritus
• Influenza-like illness

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of AHR agonists include:

• tapinarof topical