Apremilast and psoriasis in the real world: A retrospective case series

Dozier, Lauren; Bartos, Gregory; Kerdel, Francisco A.

doi:10.1016/j.jaad.2019.10.009

Cited by 10 publications

(4 citation statements)

References 3 publications

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“…Several experimental and clinical studies have demonstrated the efficacy and tolerability of these two agents in psoriasis treatment. Apremilast is a small molecule PDE-4 inhibitor lowers cytokine secretion and expression by increasing intracellular cAMP levels ( 262 ) and enhances the expression of anti-inflammatory cytokines ( 263 , 264 ). It also inhibits the activation of NF-κB and MAPK signaling pathways ( 265 ).…”

Section: Emerging Therapies Targeting Immune Cells In Psoriasismentioning

confidence: 99%

Immune cells in the epithelial immune microenvironment of psoriasis: emerging therapeutic targets

Li,

Lu,

Liu

et al. 2024

Front. Immunol.

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Psoriasis is a chronic autoimmune inflammatory disease characterized by erroneous metabolism of keratinocytes. The development of psoriasis is closely related to abnormal activation and disorders of the immune system. Dysregulated skin protective mechanisms can activate inflammatory pathways within the epithelial immune microenvironment (EIME), leading to the development of autoimmune-related and inflammatory skin diseases. In this review, we initially emphasized the pathogenesis of psoriasis, paying particular attention to the interactions between the abnormal activation of immune cells and the production of cytokines in psoriasis. Subsequently, we delved into the significance of the interactions between EIME and immune cells in the emergence of psoriasis. A thorough understanding of these immune processes is crucial to the development of targeted therapies for psoriasis. Finally, we discussed the potential novel targeted therapies aimed at modulating the EIME in psoriasis. This comprehensive examination sheds light on the intricate underlying immune mechanisms and provides insights into potential therapeutic avenues of immune-mediated inflammatory diseases.

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Section: Emerging Therapies Targeting Immune Cells In Psoriasismentioning

confidence: 99%

Immune cells in the epithelial immune microenvironment of psoriasis: emerging therapeutic targets

Li,

Lu,

Liu

et al. 2024

Front. Immunol.

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“…This newly acquired information greatly stimulated the research leading to the synthesis of Roflumilast by AstraZeneca, which was finally approved as a COPD drug in the EU (in 2010) and in the USA (in 2011) [ 70 ]. Since the marketing of Roflumilast, three additional compounds have been marketed as PDE4-inhibitor drugs ( Figure 4 ) i.e., Crisaborole (by Pfizer) for atopic dermatitis [ 71 ], Apremilast (by Celgene) for psoriatic arthritis [ 72 ] and Ibudilast (by MediciNova) for Krabbe diseases (also known as globoid cell leukodystrophy) [ 73 ]. However, research in the field of PDE4 inhibitors has remained very active, leading to very potent and pharmacologically relevant ligands that have entered clinical trials for the treatment of a range of diseases.…”

Section: From In Vitro and Preclinical Profile Of The First Pde 4 Inh...mentioning

confidence: 99%

An Overview of PDE4 Inhibitors in Clinical Trials: 2010 to Early 2022

et al. 2022

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Since the early 1980s, phosphodiesterase 4 (PDE4) has been an attractive target for the treatment of inflammation-based diseases. Several scientific advancements, by both academia and pharmaceutical companies, have enabled the identification of many synthetic ligands for this target, along with the acquisition of precise information on biological requirements and linked therapeutic opportunities. The transition from pre-clinical to clinical phase was not easy for the majority of these compounds, mainly due to their significant side effects, and it took almost thirty years for a PDE4 inhibitor to become a drug i.e., Roflumilast, used in the clinics for the treatment of chronic obstructive pulmonary disease. Since then, three additional compounds have reached the market a few years later: Crisaborole for atopic dermatitis, Apremilast for psoriatic arthritis and Ibudilast for Krabbe disease. The aim of this review is to provide an overview of the compounds that have reached clinical trials in the last ten years, with a focus on those most recently developed for respiratory, skin and neurological disorders.

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“…Most PDE4 inhibitors produce the inhibition of all four subtypes (PDE4A, PDE4B, PDE4C, and PDE4D) together with the increase in the cAMP concentration above normal physiological levels. Three PDE4 inhibitors, namely, roflumilast, apremilast, and crisaborole, have been already approved worldwide for the treatment of COPD [14], psoriatic arthritis [15], and atopic dermatitis [16], respectively. Moreover, PDE4D inhibitor ibudilast is also approved for the treatment of rare child disease Krabbe by the Food and Drug Administration (FDA) and for bronchial asthma by the Japanese authority [17].…”

Section: Pde4 Structural Biologymentioning

confidence: 99%

Insight into Inhibitory Mechanism of PDE4D by Dietary Polyphenols Using Molecular Dynamics Simulations and Free Energy Calculations

Furlan

Bren

2021

Biomolecules

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Phosphodiesterase 4 (PDE4), mainly present in immune, epithelial, and brain cells, represents a family of key enzymes for the degradation of cyclic adenosine monophosphate (cAMP), which modulates inflammatory response. In recent years, the inhibition of PDE4 has been proven to be an effective therapeutic strategy for the treatment of neurological disorders. PDE4D constitutes a high-interest therapeutic target primarily for the treatment of Alzheimer’s disease, as it is highly involved in neuroinflammation, learning ability, and memory dysfunctions. In the present study, a thorough computational investigation consisting of molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations based on the linear response approximation (LRA) method was performed to study dietary polyphenols as potential PDE4D inhibitors. The obtained results revealed that curcumin, 6-gingerol, capsaicin, and resveratrol represent potential PDE4D inhibitors; however, the predicted binding free energies of 6-gingerol, capsaicin, and resveratrol were less negative than in the case of curcumin, which exhibited the highest inhibitory potency in comparison with a positive control rolipram. Our results also revealed that the electrostatic component through hydrogen bonding represents the main driving force for the binding and inhibitory activity of curcumin, 6-gingerol, and resveratrol, while the van der Waals component through shape complementarity plays the most important role in capsaicin's inhibitory activity. All investigated compounds form hydrophobic interactions with residues Gln376 and Asn602 as well as hydrogen bonds with nearby residues Asp438, Met439, and Ser440. The binding mode of the studied natural compounds is consequently very similar; however, it significantly differs from the binding of known PDE4 inhibitors. The uncovered molecular inhibitory mechanisms of four investigated natural polyphenols, curcumin, 6-gingerol, capsaicin, and resveratrol, form the basis for the design of novel PDE4D inhibitors for the treatment of Alzheimer’s disease with a potentially wider therapeutic window and fewer adverse side effects.

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Apremilast and psoriasis in the real world: A retrospective case series

Cited by 10 publications

References 3 publications

Immune cells in the epithelial immune microenvironment of psoriasis: emerging therapeutic targets

Immune cells in the epithelial immune microenvironment of psoriasis: emerging therapeutic targets

An Overview of PDE4 Inhibitors in Clinical Trials: 2010 to Early 2022

Insight into Inhibitory Mechanism of PDE4D by Dietary Polyphenols Using Molecular Dynamics Simulations and Free Energy Calculations

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