Comparison of the effects of vitamin D products in a psoriasis plaque test and a murine psoriasis xenograft model.
The aim of the present study was to compare the effects of Daivobet and calcipotriol on clinical score and biomarker responses in a modified version of the Scholtz-Dumas psoriasis plaque assay. Furthermore, it was the aim to compare the effects of calcipotriol and betamethasone in the murine psoriasis xenograft model. Twenty four patients with psoriasis were treated topically once daily for three weeks, whereas the grafted mice were treated for four weeks. Clinical responses were scored twice weekly and biopsies were taken at the end of each study to analyse for skin biomarkers by histology and immunohistochemistry. The results clearly demonstrate effects on both clinical signs and biomarkers. In the patient study the total clinical score was reduced significantly with both Daivobet and calcipotriol. Both treatments reduced epidermal thickness, Ki-67 and cytokeratin 16 expression. T cell infiltration was significantly reduced by Daivobet but only marginally by calcipotriol. Both treatments showed strong effects on the epidermal psoriatic phenotype.Results from the xenograft model essentially showed the same results. However differences were observed when investigating subtypes of T cells.The study demonstrates the feasibility of obtaining robust biomarker data in the psoriasis plaque test that correlate well with those obtained in other clinical studies. Furthermore, the biomarker data from the plaque test correlate with biopsy data from the grafted mice.
Kvist
Peter H
PH
Department of Disease Pharmacology, LEO Pharma A/S, Industriparken 55, DK-2750 Ballerup, Denmark. phkv@novonordisk.com
Svensson
Lars
L
Hagberg
Oskar
O
Hoffmann
Vibeke
V
Kemp
Kaare
K
Røpke
Mads A
MA
D000818:Animals; D001623:Betamethasone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003879:Dermatologic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004338:Drug Combinations; D023381:Endpoint Determination; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012882:Skin Tests; D014183:Transplantation, Heterologous; D014807:Vitamin D / Q000494:pharmacology / Q000627:therapeutic use*
D015415:Biomarkers; D003879:Dermatologic Agents; D004338:Drug Combinations; C517164:betamethasone dipropionate, calcipotriol drug combination; D014807:Vitamin D; C055085:calcipotriene; D001623:Betamethasone; D002117:Calcitriol