TY - JOUR
T1 - The role of phosphodiesterase 4 in the pathophysiology of atopic dermatitis and the perspective for its inhibition
AU - Guttman-Yassky, Emma
AU - Hanifin, Jon M.
AU - Boguniewicz, Mark
AU - Wollenberg, Andreas
AU - Bissonnette, Robert
AU - Purohit, Vivek
AU - Kilty, Iain
AU - Tallman, Anna M.
AU - Zielinski, Michael A.
N1 - Funding Information:
Editorial/medical writing support under the guidance of the authors was provided by Corey Mandel, PhD, and Robert Schoen, PharmD (ApotheCom, San Francisco, CA) and was funded by Pfizer Inc., New York, NY, U.S.A., in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med 2015; 163:461–4).
Funding Information:
EG-Y is an employee of Mount Sinai and has received research funds (grants paid to her institution) from AbbVie, Celgene, Eli Lilly, Janssen Pharmaceuticals, MedImmune/AstraZeneca, Novartis, Pfizer, Regeneron, Vitae, Glenmark, Galderma, Asana BioSciences, Innovaderm, Dermira, and UCB; she is also a consultant for Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor Pharmaceuticals, a wholly owned subsidiary of Pfizer Inc., AnaptysBio, Dermira, Galderma, Glenmark, Novartis, Pfizer, Vitae, LEO Pharma, AbbVie, Eli Lilly, Kyowa, Mitsubishi Tanabe, Asana BioSciences, and Promius. JH has provided consulting services for Menlo Therapeutics, AbbVie, GlaxoSmithKline, Anacor Pharmaceuticals, a wholly owned subsidiary of Pfizer Inc., Otsuka Pharmaceutical, Dermira, F. Hoffman-La Roche., and Chugai Pharmaceutical; he has also received study support from GlaxoSmithKline, Otsuka Pharmaceutical, and Merck. MB has received a research grant from Anacor Pharmaceuticals, a wholly owned subsidiary of Pfizer Inc. AW has been an advisor for Anacor Pharmaceuticals, a wholly owned subsidiary of Pfizer Inc. and Pfizer, and has received honoraria for consultancy and lectures in the field of atopic dermatitis from Almirall, Anacor, Astellas, Celgene, Chugai, Galderma, LEO Pharma, L’Oreal, MEDA, MedImmune, Novartis, Pierre Fabre, Pfizer, Regeneron, and Sanofi. RB was an investigator, consultant, advisory board member, speaker for, and/ or received honoraria from Antibiotox, Aquinox, Asana BioSciences, Astellas, Brickell, Dermavant, Dermira, Dignity Sciences, Galderma, Glenmark, Stiefel/GlaxoSmithKline, F. Hoffman-La Roche, LEO Pharma, NeoKera, Pfizer, Regeneron, and Vitae. VP, IK, and MAZ are shareholders and employees of Pfizer Inc. AMT is a former employee and former shareholder of Pfizer Inc.
PY - 2019/1
Y1 - 2019/1
N2 - Atopic dermatitis (AD) is a highly prevalent, chronic inflammatory skin disease that affects children and adults. The pathophysiology of AD is complex and involves skin barrier and immune dysfunction. Many immune cytokine pathways are amplified in AD, including T helper (Th) 2, Th22, Th17 and Th1. Current treatment guidelines recommend topical medications as initial therapy; however, until recently, only two drug classes were available: topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs). Several limitations are associated with these agents. TCSs can cause a wide range of adverse effects, including skin atrophy, telangiectasia, rosacea and acne. TCIs can cause burning and stinging, and the prescribing information lists a boxed warning for a theoretical risk of malignancy. Novel medications with new mechanisms of action are necessary to provide better long-term control of AD. Phosphodiesterase 4 (PDE4) regulates cyclic adenosine monophosphate in cells and has been shown to be involved in the pathophysiology of AD, making it an attractive therapeutic target. Several PDE4 inhibitors are in clinical development for use in the treatment of AD, including crisaborole, which recently became the first topical PDE4 inhibitor approved for treatment of mild to moderate AD. This review will further describe the pathophysiology of AD, explain the possible role of PDE4 in AD and review PDE4 inhibitors currently approved or being investigated for use in AD.
AB - Atopic dermatitis (AD) is a highly prevalent, chronic inflammatory skin disease that affects children and adults. The pathophysiology of AD is complex and involves skin barrier and immune dysfunction. Many immune cytokine pathways are amplified in AD, including T helper (Th) 2, Th22, Th17 and Th1. Current treatment guidelines recommend topical medications as initial therapy; however, until recently, only two drug classes were available: topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs). Several limitations are associated with these agents. TCSs can cause a wide range of adverse effects, including skin atrophy, telangiectasia, rosacea and acne. TCIs can cause burning and stinging, and the prescribing information lists a boxed warning for a theoretical risk of malignancy. Novel medications with new mechanisms of action are necessary to provide better long-term control of AD. Phosphodiesterase 4 (PDE4) regulates cyclic adenosine monophosphate in cells and has been shown to be involved in the pathophysiology of AD, making it an attractive therapeutic target. Several PDE4 inhibitors are in clinical development for use in the treatment of AD, including crisaborole, which recently became the first topical PDE4 inhibitor approved for treatment of mild to moderate AD. This review will further describe the pathophysiology of AD, explain the possible role of PDE4 in AD and review PDE4 inhibitors currently approved or being investigated for use in AD.
KW - calcineurin inhibitor
KW - corticosteroids
KW - crisaborole
KW - cytokines
KW - eczema
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U2 - 10.1111/exd.13808
DO - 10.1111/exd.13808
M3 - Review article
C2 - 30332502
AN - SCOPUS:85058312582
VL - 28
SP - 3
EP - 10
JO - Experimental Dermatology
JF - Experimental Dermatology
SN - 0906-6705
IS - 1
ER -