Anti-inflammatory potency testing of topical corticosteroids and calcineurin inhibitors in human volunteers sensitized to diphenylcyclopropenone

TY - JOUR

T1 - Anti-inflammatory potency testing of topical corticosteroids and calcineurin inhibitors in human volunteers sensitized to diphenylcyclopropenone

AU - Mose, Kristian F

AU - Andersen, Flemming

AU - Røpke, Mads A

AU - Skov, Lone

AU - Friedmann, Peter S

AU - Andersen, Klaus E

N1 - © 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

PY - 2018/8

Y1 - 2018/8

N2 - Aims: To quantify the anti-inflammatory potency of topical corticosteroids and topical calcineurin inhibitors by measuring the contact allergic response to a diphenylcyclopropenone (DPCP) challenge in de novo sensitized human volunteers. Methods: Two randomized, double-blind, vehicle-controlled studies were performed encompassing 76 volunteers: 29 in the first and 47 in the second study. Topical drugs were applied pre- and/or post-treatment in block designs. The compounds were tested simultaneously under occluded patch tests covering DPCP-induced dermatitis. Inhibitory responses were assessed by visual scoring and measurements of the oedema thickness with ultrasound. Results: When applied both before and after the DPCP challenge, significant anti-inflammatory effects were seen in descending order for tacrolimus 0.1% ointment, clobetasol propionate ointment, betamethasone valerate ointment and hydrocortisone butyrate ointment, while pimecrolimus cream, hydrocortisone ointment and vehicles had no significant effect. Only tacrolimus ointment (P < 0.01) demonstrated a consistent significant pre-treatment inhibitory effect compared with an untreated DPCP control. Conclusions: This human testing method in which the inflammation of experimentally induced allergic patch test reactions is quantified by objective measurement allows an analysis of the anti-inflammatory potency of not only topical corticosteroids, but also of drugs that have no effect on vasoconstriction. The method allowed comparison of the potencies of four topical corticosteroids and two calcineurin inhibitors.

AB - Aims: To quantify the anti-inflammatory potency of topical corticosteroids and topical calcineurin inhibitors by measuring the contact allergic response to a diphenylcyclopropenone (DPCP) challenge in de novo sensitized human volunteers. Methods: Two randomized, double-blind, vehicle-controlled studies were performed encompassing 76 volunteers: 29 in the first and 47 in the second study. Topical drugs were applied pre- and/or post-treatment in block designs. The compounds were tested simultaneously under occluded patch tests covering DPCP-induced dermatitis. Inhibitory responses were assessed by visual scoring and measurements of the oedema thickness with ultrasound. Results: When applied both before and after the DPCP challenge, significant anti-inflammatory effects were seen in descending order for tacrolimus 0.1% ointment, clobetasol propionate ointment, betamethasone valerate ointment and hydrocortisone butyrate ointment, while pimecrolimus cream, hydrocortisone ointment and vehicles had no significant effect. Only tacrolimus ointment (P < 0.01) demonstrated a consistent significant pre-treatment inhibitory effect compared with an untreated DPCP control. Conclusions: This human testing method in which the inflammation of experimentally induced allergic patch test reactions is quantified by objective measurement allows an analysis of the anti-inflammatory potency of not only topical corticosteroids, but also of drugs that have no effect on vasoconstriction. The method allowed comparison of the potencies of four topical corticosteroids and two calcineurin inhibitors.

U2 - 10.1111/bcp.13596

DO - 10.1111/bcp.13596

M3 - Journal article

C2 - 29607554

SN - 0264-3774

VL - 84

SP - 1719

EP - 1728

JO - British Journal of Clinical Pharmacology, Supplement

JF - British Journal of Clinical Pharmacology, Supplement

IS - 8

ER -