Psoriasis: Targets and Therapy (Mar 2021)
Phosphodiesterase-4 Inhibition in Psoriasis
Abstract
Milica Milakovic,1 Melinda J Gooderham2– 4 1Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 2Skin Centre for Dermatology, Peterborough, ON, K9J 5K2, Canada; 3Probity Medical Research, Waterloo, ON, N2J 1C4, Canada; 4Department of Medicine, Queen’s University, Kingston, ON, K7L 3N6, CanadaCorrespondence: Melinda J GooderhamSkin Centre for Dermatology, 775 Monaghan Road, Peterborough, ON, K9J 5K2, CanadaTel +1 705 775 7546Fax +1 705 775 3376Email [email protected]: Psoriasis is a chronic immune-mediated inflammatory disorder. Phosphodiesterase-4 (PDE-4) is an enzyme that mediates inflammatory responses and plays a role in psoriasis pathogenesis. PDE-4 degrades its substrate cyclic adenosine monophosphate (cAMP) to adenosine monophosphate (AMP), which subsequently leads to the production of pro-inflammatory mediators. Inhibitors of PDE-4 work by blocking the degradation of cAMP, which leads to a reduction in inflammation. Apremilast is the only approved oral PDE-4 inhibitor for the treatment of psoriasis. While it is effective for some patients, it may be limited by adverse effects in others. A topical PDE-4 inhibitor, roflumilast, is being investigated in psoriasis and showing promising results. Crisaborole, a topical PDE-4 inhibitor approved for use in atopic dermatitis, has also been investigated in psoriasis. This is an updated comprehensive review to summarize the currently available evidence for the PDE-4 inhibitors apremilast, roflumilast and crisaborole in the treatment of psoriasis, with a focus on data from randomized clinical trials.Keywords: psoriasis, PDE-4, phosphodiesterase inhibitors, topical therapies
