Topical R-85355, a potent and selective 5-lipoxygenase inhibitor, fails to improve psoriasis

Inhibitors of 5-lipoxygenase have been studied with respect to antipsoriatic efficacy. Of these compounds, R-68151 is of particular interest as it proved to inhibit 5-lipoxygenase without inhibiting 12-lipoxygenase, cyclooxygenase and thromboxane-A2 synthetase. R-68151 has been shown to have a mild-to-moderate therapeutic effect in psoriasis. In the present study a new 5-lipoxygenase, R-85355, was investigated with respect to its efficacy in psoriasis. R-85355 is 3 times more potent compared to R-68151 with respect to inhibition of in vitro A-23187-stimulated leukotriene-B4 production by polymorphonuclear leukocytes. In a left-right double-blind comparative study, the compound was studied at saturation with respect to its antipsoriatic efficacy in 11 patients with chronic stable plaque psoriasis. In addition, various markers for epidermal proliferation, keratinization and inflammation were assessed. In no single patient was a left-right difference observed in favour of R-85355 compared to placebo with respect to clinical severity scores or the cell-biological markers. The present study indicates that a selective and highly potent 5-lipoxygenase inhibitor was not effective in the topical treatment of chronic plaque psoriasis.