The effect of long-term treatment with tacalcitol on the psoriatic epidermis. A flow cytometric analysis

Abstract

During the last decade, novel analogues of 1alpha,25-dihydroxy vitamin D3 have been developed for the treatment of psoriasis. Recently, the efficacy of short-term treatment with the novel derivative tacalcitol (1alpha,24-dihydroxy vitamin D3) has been documented. However, data on the long-term effect of tacalcitol on psoriatic skin are sparse. In this study, we assessed the cell characteristics of the psoriatic epidermis after treatment with tacalcitol for up to 24 weeks. We investigated how long-term treatment with tacalcitol modulates the percentages of differentiated keratinocytes, inflammation cells and basal keratinocytes, and the percentage of cells in the SG2M phase in the basal cell population. From 11 patients who were treated with tacalcitol for up to 18 months, we obtained single-cell suspensions of a representative psoriatic lesion after 0, 8, 12, 18 and 24 weeks of treatment. A Psoriasis Area and Severity Index was performed at each visit as well. Cell suspensions were stained with markers for inflammation (Vim3B4), differentiation (RKSE60) and proliferation (TO-PRO-3 iodide) and analysed flow cytometrically. Clinically, patients improved significantly after 8 weeks of treatment. This clinical effect was preserved for the rest of the period of treatment with no further significant improvement. Proliferative activity also decreased significantly after 8 weeks of treatment. Proliferation did not show further significant decreases or habituation after 12, 18 and 24 weeks. For inflammation, no statistically reliable trends could be seen. Differentiation improved significantly after 8 weeks of treatment, but decreased again significantly after 12 weeks. In the period from 12 to 24 weeks, no further significant change was observed. We conclude that tacalcitol is an effective antipsoriatic drug. Prolonged treatment with tacalcitol will generally maintain improvement at the level reached after 8 weeks. Owing to the beneficial effect on both clinical state and proliferation, tacalcitol is likely to be an adequate maintenance therapy.

Influence of Tacalcitol on Cell Cycle Kinetics of Human Keratinocytes following Standardized Injury

“…This is in contrast with studies which showed that tacalcitol affects keratinization to some extent [2,7,24]. However, most authors conclude that the effect of tacalcitol on differentiation is limited [4,6,8].…”

“…Several in vitro and in vivo studies showed the effect of tacalcitol on epidermal proliferation and differentiation, and the effect on inflammatory processes in skin [2][3][4][5][6][7][8]. Especially the effect on epidermal proliferation has shown to be most substantial [2,6,7]. This finding strongly suggests that the antipsoriatic effect of tacalcitol may be mediated by the normalization of epidermal cell cycle kinetics.…”

“…The drug is now available in Japan, the UK, Germany, Switzerland and several other European countries for the topical treatment of this disease [1]. Several in vitro and in vivo studies showed the effect of tacalcitol on epidermal proliferation and differentiation, and the effect on inflammatory processes in skin [2][3][4][5][6][7][8]. Especially the effect on epidermal proliferation has shown to be most substantial [2,6,7].…”

In Vivo Effects of Topical Anti-Psoriatic Treatments on Cutaneous Inflammation, Epidermal Proliferation and Keratinisation

“…Ki-67 (-) 48 [16],71 [23] 35 [29],44 [24],69 [20] 70 [19] 77 [22] 84 [27] K10 (+) 22 [30],11 [34] 22 [29], 66 [25] 100 [31] SG2M (-) 26 [34],33 [15],34 [30] 44 [25] 71 [31] K16 (-) 26 [16],60 [15] 83 [24] 47 [22] Involucrin (-) [34] 61 [31] 45 [30] 85 [34] All vitamin D 3 analogues had a clear inhibitory effect on neutrophils [16,19,20].…”

“…As can be seen in Table 2, calcipotriol, tacalcitol and betamethasone have varying effects on the percentage of vimentin+ cells. A substantial reduction of vimentin+ cells is reached by clobetasol and the combinations of calcipotriol with a corticosteroid [25,[29][30][31]34].…”