Mechanisms Underlying the Clinical Effects of Apremilast for Psoriasis
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Mechanisms Underlying the Clinical Effects of Apremilast for Psoriasis. / Pincelli, Carlo; Schafer, Peter H; French, Lars E; Augustin, Matthias; Krueger, James G.
in: J DRUGS DERMATOL, Jahrgang 17, Nr. 8, 01.08.2018, S. 835-840.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Review › Forschung
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TY - JOUR
T1 - Mechanisms Underlying the Clinical Effects of Apremilast for Psoriasis
AU - Pincelli, Carlo
AU - Schafer, Peter H
AU - French, Lars E
AU - Augustin, Matthias
AU - Krueger, James G
PY - 2018/8/1
Y1 - 2018/8/1
N2 - Psoriasis is a chronic, systemic, inflammatory disease with manifestations resulting from a dysregulated immune response. In psoriatic skin, expression of all phosphodiesterase 4 (PDE4) isoforms (A-D), part of a family of enzymes known to regulate cyclic adenosine monophosphate levels and immune homeostasis, is elevated compared with healthy controls. Agents that inhibit the enzymatic activity of PDE4, the predominant PDE in most immune cells, exert well-recognized anti-inflammatory effects. Apremilast is a selective PDE4 inhibitor approved for the treatment of adults with moderate to severe plaque psoriasis and/or psoriatic arthritis. In vitro and in vivo investigations have demonstrated the beneficial impact of apremilast treatment on PDE4 activity, inflammatory signal expression, and dermal psoriasiform signs. In patients with moderate to severe psoriasis, treatment with apremilast is associated with significant reductions in plasma levels of interleukin (IL)-17F, IL-17A, IL-22, and tumor necrosis factor-α compared with placebo as early as week 4; decreases in cytokine levels were sustained with continued treatment. Multivariate analyses demonstrated that while changes in IL-17F are the most important predictor of improvement in Psoriasis Area and Severity Index scores, apremilast exerts synergistic attenuating effects among a key group of cytokines involved in the pathology of psoriasis, and these effects correlate with improved skin symptoms. These in vitro and clinical data demonstrate that the beneficial effects of apremilast on known inflammatory mediators are associated with its clinical efficacy. J Drugs Dermatol. 2018;17(8):835-840. THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS..
AB - Psoriasis is a chronic, systemic, inflammatory disease with manifestations resulting from a dysregulated immune response. In psoriatic skin, expression of all phosphodiesterase 4 (PDE4) isoforms (A-D), part of a family of enzymes known to regulate cyclic adenosine monophosphate levels and immune homeostasis, is elevated compared with healthy controls. Agents that inhibit the enzymatic activity of PDE4, the predominant PDE in most immune cells, exert well-recognized anti-inflammatory effects. Apremilast is a selective PDE4 inhibitor approved for the treatment of adults with moderate to severe plaque psoriasis and/or psoriatic arthritis. In vitro and in vivo investigations have demonstrated the beneficial impact of apremilast treatment on PDE4 activity, inflammatory signal expression, and dermal psoriasiform signs. In patients with moderate to severe psoriasis, treatment with apremilast is associated with significant reductions in plasma levels of interleukin (IL)-17F, IL-17A, IL-22, and tumor necrosis factor-α compared with placebo as early as week 4; decreases in cytokine levels were sustained with continued treatment. Multivariate analyses demonstrated that while changes in IL-17F are the most important predictor of improvement in Psoriasis Area and Severity Index scores, apremilast exerts synergistic attenuating effects among a key group of cytokines involved in the pathology of psoriasis, and these effects correlate with improved skin symptoms. These in vitro and clinical data demonstrate that the beneficial effects of apremilast on known inflammatory mediators are associated with its clinical efficacy. J Drugs Dermatol. 2018;17(8):835-840. THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS..
KW - Animals
KW - Anti-Inflammatory Agents, Non-Steroidal
KW - Humans
KW - Inflammation Mediators
KW - Interleukin-17
KW - Interleukins
KW - Phosphodiesterase 4 Inhibitors
KW - Psoriasis
KW - Thalidomide
KW - Treatment Outcome
KW - Journal Article
KW - Review
M3 - SCORING: Review article
C2 - 30124722
VL - 17
SP - 835
EP - 840
JO - J DRUGS DERMATOL
JF - J DRUGS DERMATOL
SN - 1545-9616
IS - 8
ER -