Phosphodiesterase 4 Inhibitor Therapies for Atopic Dermatitis: Progress and Outlook

Ahluwalia, Jusleen; Udkoff, Jeremy; Waldman, Andrea; Borok, Jenna; Eichenfield, Lawrence F.

doi:10.1007/s40265-017-0784-3

Cited by 33 publications

(28 citation statements)

References 32 publications

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“…84 PDE4 antagonism inhibits production of many inflammatory mediators, including T H 1related (IFN-g), T H 2-related (IL-5), and T H 17-related (IL-8) products in model systems. 15,48,51,[81][82][83][85][86][87][88] In patients with psoriasis treated with the systemic PDE4 inhibitor apremilast, the greatest molecular inhibition is observed for T H 17/T H 22 pathway genes (IL17, IL22, and IL23). 42,51,80,[89][90][91][92][93] T H 17/T H 22centered suppression was also observed in AD lesions in patients treated with 40 mg of apremilast.…”

Section: Discussionmentioning

confidence: 99%

Crisaborole and atopic dermatitis skin biomarkers: An intrapatient randomized trial

Bissonnette

Pavel

Diaz

et al. 2019

Journal of Allergy and Clinical Immunology

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Downregulated Skin Biomarkers Upregulated Crisaborole Vehicle Crisaborole Day 15 Day 8 Day 1 Day 15 Day 8 Day 1 Vehicle Day 1 NL CRISABOROLE AND ATOPIC DERMATITIS SKIN BIOMARKERS: AN INTRAPATIENT RANDOMIZED TRIAL 2 AD lesions of identical severity were randomized intrapatient to crisaborole or vehicle and biopsied at days 1, 8, and 15 (including Th2 and Th17/Th22 axes) and improved barrier function NL skin biopsied at day 1 AD, atopic dermatitis; NL, nonlesional; Th, helper T cellBackground: Crisaborole ointment 2% is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-tomoderate atopic dermatitis (AD). The mechanism of action of crisaborole and its effects on lesional measures of disease severity are not yet well defined. Objective: This phase 2a, single-center, vehicle-controlled, intrapatient study was designed to further characterize the mechanism of action of crisaborole through evaluation of clinical efficacy and changes in skin biomarkers in adults (n 5 40) with mild-to-moderate AD. Methods: Two target lesions were randomized in an intrapatient (1:1) manner to double-blind crisaborole/vehicle applied twice daily for 14 days. Patients then applied crisaborole (open-label) to all affected areas for 28 days. Punch biopsy specimens were collected for biomarker analysis at baseline, day 8 (optional), and day 15.

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Section: Discussionmentioning

confidence: 99%

Crisaborole and atopic dermatitis skin biomarkers: An intrapatient randomized trial

Bissonnette

Pavel

Diaz

et al. 2019

Journal of Allergy and Clinical Immunology

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“…In the 1980s, enhanced PDE activity was determined in blood cells as well as cord blood cells of patients with AD [204]. Since then, the effects of PDE inhibitors in patients with AD have been demonstrated [205].…”

Section: Phosphodiesterase (Pde) Inhibitorsmentioning

confidence: 99%

Childhood atopic dermatitis: current developments, treatment approaches, and future expectations

Çetinkaya¹,

Şahiner²

2019

Turk J Med Sci

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Atopic dermatitis (AD) is the most common chronic inflammatory skin disorder of childhood. Underlying factors that contribute to AD are impaired epithelial barrier, alterations in the lipid composition of the skin, immunological imbalance including increased Th2/Th1 ratio, proinflammatory cytokines, decreased T regulatory cells, genetic mutations, and epigenetic alterations. Atopic dermatitis is a multifactorial disease with a particularly complicated pathophysiology. Discoveries to date may be considered the tip of the iceberg, and the increasing number of studies in this field indicate that there are many points to be elucidated in AD pathophysiology. In this review, we aimed to illustrate the current understanding of the underlying pathogenic mechanisms in AD, to evaluate available treatment options with a focus on recently discovered therapeutic agents, and to determine the personal, familial, and economic burdens of the disease, which are frequently neglected issues in AD. Currently available therapies only provide transient solutions and cannot fully cure the disease. However, advances in the understanding of the pathogenic mechanisms of the disease have led to the production of new treatment options, while ongoing drug trials also have had promising results.

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“…Phosphodiesterase 4 (PDE4) is a cyclic AMP degrading enzyme in leukocytes. Increased PDE activity had been demonstrated in patients with atopic dermatitis (AD) several years ago, while several PDE4 inhibitors in topical formulation have been developed to target the inflammatory cascade of AD (Ahluwalia, Udkoff, Waldman, Borok, & Eichenfield, ). Simultaneously, the therapeutic effect and safety of PDE4 inhibitors have been confirmed on psoriasis, while it was approved for psoriatic arthritis and plaque psoriasis by FDA in 2014, European Commission in 2015, and recommended by European S3‐Guidelines in 2017 (Fala, ; Nast et al, ).…”

Section: Small Moleculesmentioning

confidence: 99%

“…IL-17 inhibitor (secukinumab, ixekizumab, brodalumab), and IL-23 inhibitor (guselkumab), as emerging therapeutic option for adult psoriasis, has rare studies in the literature investigating the use of these in pediatric psoriasis. Increased PDE activity had been demonstrated in patients with atopic dermatitis (AD) several years ago, while several PDE4 inhibitors in topical formulation have been developed to target the inflammatory cascade of AD(Ahluwalia, Udkoff, Waldman, Borok, & Eichenfield, 2017). Simultaneously, the therapeutic effect and safety of PDE4 inhibitors have been confirmed on psoriasis, while it was approved for psoriatic arthritis and plaque psoriasis by FDA in 2014, European Commission in 2015, and recommended by European S3-Guidelines in 2017(Fala, 2015;Nast et al, 2017). 3.1 | PDE4 inhibitor for treatment of AD 7%) crisaborole 2% ointment recipients (vs. 2.4% of vehicle recipients) and did not consider to be related to the study medication.…”

mentioning

confidence: 99%

Pediatric Dermatology ‐ critical approach to the new treatments

Liang

Chen

Zhao

et al. 2018

Dermatologic Therapy

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The field of pediatric dermatology treatment has been rich in new developments. Several recent therapeutic advances in pediatric dermatology have been made. This review will focus on critical approach to the new treatments for several entities encountered in pediatric dermatology. The use of biologics and small molecules in children with atopic dermatitis and psoriasis, exciting advances in the use of propranolol and other beta‐blockers for the treatment of infantile hemangiomas, the use of sirolimus for vascular anomalies will be discussed.

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Phosphodiesterase 4 Inhibitor Therapies for Atopic Dermatitis: Progress and Outlook

Cited by 33 publications

References 32 publications

Crisaborole and atopic dermatitis skin biomarkers: An intrapatient randomized trial

Crisaborole and atopic dermatitis skin biomarkers: An intrapatient randomized trial

Childhood atopic dermatitis: current developments, treatment approaches, and future expectations

Pediatric Dermatology ‐ critical approach to the new treatments

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