Topical maxacalcitol for the treatment of psoriasis vulgaris: a placebo-controlled, double-blind, dose-finding study with active comparator

Abstract

1alpha, 25-Dihydroxy-22-oxacalcitriol (maxacalcitol) is a vitamin D3 analogue which displays approximately 10 times greater efficacy at suppressing keratinocyte proliferation in vitro than calcipotriol and tacalcitol. To determine clinical efficacy, a phase II double-blind, randomized, left vs. right, concentration-response study was performed with once-daily topical maxacalcitol in patients with mild to moderate chronic plaque psoriasis. Primary efficacy parameters were psoriasis severity index (PSI) based on sum of scores for erythema, scaling and induration and investigators' overall assessment of patients' response to therapy at 8 weeks of treatment. One hundred and forty-four patients participated. All concentrations of maxacalcitol ointment (6, 12.5, 25 and 50 microg/g) were significantly more effective at reducing PSI than placebo (P < 0.01), with greatest effect noted for maxacalcitol 25 microg/g. Calcipotriol ointment 50 microg/g once daily as active comparator had a similar effect. Marked improvement or clearance of psoriasis was greatest for maxacalcitol 25 microg/g (55% of subjects) which compared favourably with calcipotriol (46%). Improvement continued throughout the study period, with no plateau at week 8. Investigators' and patients' side preference (secondary efficacy parameters) rated maxacalcitol more effective than placebo and 25 microg/g maxacalcitol better than calcipotriol (P < 0.05 for investigators' assessment). Twelve patients withdrew from the study due to adverse events, of which four were judged to be due to study medication. This study indicates that once-daily maxacalcitol ointment is effective in the management of plaque psoriasis, with greatest effect noted at 25 microg/g. As no response plateau was noted at 8 weeks, these data suggest that further benefit might be obtained if maxacalcitol ointment were applied for longer. Finally, investigators' overall assessment and side preference suggest that maxacalcitol 25 microg/g may be more effective than once-daily calcipotriol.

Immunomodulating effect of vitamin D3 derivatives on type-1 cellular immunity

“…Therefore, it is speculated that VitD3 derivatives may be useful for the therapy of Th1-dependent immune diseases. Indeed, recently, it has been reported that VitD3 derivative is effective against psoriasis in human and experimental autoimmune encephalomyelitis in animal models (4,5,18,23). However, the precise mechanism has remained unclear yet.…”

“…Psoriasis is an autoimmune disease, which is induced by abnormal acceleration of type-1 immune responses (14). Recently, it has been reported that topical 22-Oxa-1α,25-D 3 (maxacalcitol) is effective for the treatment of psoriasis (4,18). It remains unclear how VitD3 derivatives show their therapeutic effect against psoriasis.…”

A vitamin D analog inhibits Th2 cytokine- and TGFβ -induced periostin production in fibroblasts: a potential role for vitamin D in skin sclerosis

“…OCT is the most used vitamin D3 analog in Japan, which displays approximately 10 times greater efficacy at suppressing keratinocyte proliferation in vitro compared with calcipotriol and tacalcitol. 20 We found that OCT significantly suppressed the expression of IL-4 and IL-13-induced POSTN in dermal fibroblasts. We hypothesize that decreased POSTN expression might be one of the mechanisms by which topical treatment with a vitamin D analog is effective in scleroderma, especially in LS.…”

Állásfoglalás

“…Ennek magyarázata lehet, hogy az aktív Dvitamin gyorsítja a keratocyták differenciálódá sát és gátolja a proliferációjukat [47,48,49], ugyan akkor előnyösen hat a betegség kialakulásában szerepet játszó immunfolyamatokra is [50]. Napjainkban a be tegség egyik alapkezelése az ideális Dvitaminszint biztosítása mellett alkalmazott kalcitriol vagy a kevéssé hypercalcaemizáló Dvitaminanalógok (kalcipotriol, ta kalcitol, maxakalcitol) lokális használata [51,52,53,54,55,56,57].…”