Crisaborole 2% Ointment for Mild-to-Moderate Atopic Dermatitis

Aryan Riahi, BSc; Joseph M. Lam, MD, FRCPC


Skin Therapy Letter. 2021;26(1) 

In This Article

Crisaborole's Mechanism of Action

Crisaborole inhibits the action of PDE4. Pharmaceutical interest in phosphodiesterase enzymes, including crisaborole, was sparked by their role in nucleotide signaling pathways, leading to the development of specific novel inhibitors.[28] Elevated PDE4 enzyme levels have been associated with a chronic inflammatory state.[29] Since PDE4 is expressed by immune cells and keratinocytes, inhibition of PDE4 increases intracellular levels of cyclic adenosine monophosphate (cAMP) which inhibits the nuclear factor kappa B (NF-kB) pathway and the release of tumor necrosis factor (TNF)-alpha and pro-inflammatory cytokines that have a causal role in AD and psoriasis.[29]

Crisaborole's boron chemistry allows for formation of a low molecular weight molecule that penetrates human skin effectively.[30] Systemic exposure and risk of adverse effects from crisaborole is generally avoided due to the molecule's rapid metabolism to inactive metabolites that do not affect cytokine release or the activity of PDE4.[29]