Chemical compound
Crisaborole, sold under the brand name Eucrisa among others, is a nonsteroidal topical medication used for the treatment of mild-to-moderate atopic dermatitis (eczema) in adults and children.[1][2][3][4]
The most common side effects are reactions at the application site (including burning or stinging).[3]
Crisaborole is a phosphodiesterase 4 (PDE-4) inhibitor, although its specific mechanism of action in atopic dermatitis is not known.[1][2]
Side effects
At the site of application, crisaborole may cause burning or stinging. Rarely, there may be an allergic reaction.[5]
Medical uses
In the US, crisaborole is indicated for topical treatment of mild to moderate atopic dermatitis in people three months of age and older.[2]
In the EU, crisaborole was authorized for treatment of mild to moderate atopic dermatitis in people two years of age and older with ≤ 40% body surface area (BSA) affected.[3]
Pharmacology
Pharmacodynamics
Crisaborole is a phosphodiesterase-4 inhibitor, mainly acting on phosphodiesterase 4B (PDE4B), which causes inflammation.[6] Chemically, crisaborole is a phenoxybenzoxaborole.[6] Inhibition of PDE4B appears to suppress the release of tumor necrosis factor alpha (TNFα), interleukin-12 (IL-12), IL-23 and other cytokines, proteins believed to be involved in the immune response and inflammation.[6]
People with atopic dermatitis produce high levels of proteins called cytokines, which can cause the inflammation of the skin seen in dermatitis.[3] Crisaborole blocks the release of certain cytokines involved in the inflammation process such as tumor necrosis factor alpha, interleukins (IL‑2, IL-4, IL-5), and interferon gamma.[3] By blocking their release, crisaborole is expected to ease the inflammation and therefore relieve symptoms of the disease.[3]
Chemistry
Crisaborole (chemical name: 4-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-5-yl)oxy]benzonitrile) is a member of the class of benzoxaboroles characterized by the presence of a boronic acid hemiester with a phenolic ether and a nitrile.[7] Crisaborole crystallizes into two polymorphs that differ in the conformation of the oxaborole ring. A cocrystal with 4,4'-bipyridine has been prepared and studied by X-ray crystallography.[8]
History
Crisaborole was developed by Anacor Pharmaceuticals for the topical treatment of psoriasis.[9][6][10] During preclinical and clinical development, crisaborole was called AN2728 and PF-06930164.[11] The drug was assumed to be potential $2bn-a-year blockbuster, when Pfizer acquired Anacor Pharmaceuticals.[12] However, the drug was commercially not successful, reaching only US$147 million in sales in 2018, and US$138 million in sales in 2019.[13]
Crisaborole was approved for use in the United States in December 2016[14][1] and for use in Canada in June 2018.[15]
The safety and efficacy of crisaborole were established in two placebo-controlled trials with a total of 1,522 participants ranging in age from two years of age to 79 years of age, with mild to moderate atopic dermatitis.[1] In both trials participants received treatment with either crisaborole or placebo twice daily for 28 days.[16] Neither the participants nor the health care providers knew which treatment was being given until after the trials were completed.[16] Overall, participants receiving crisaborole achieved greater response with clear or almost clear skin after 28 days of treatment.[1][16] The trials were conducted in the US.[16]
Crisaborole, approved for the treatment of mild to moderate atopic dermatitis in the European Union, has been rapidly withdrawn from the European market (March 2020 - February 2022).[3]
