Treatment of psoriasis with calcipotriol and other vitamin D analogues

The discovery of a high-affinity receptor for the bioactive form of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25[OH]D3), in most skin cells has led to the finding of previously unknown effects of vitamin D on epidermal growth and on the skin immune system. 1,25(OH)2D3 inhibits epidermal proliferation and promotes epidermal differentiation. These properties provided the rationale for introducing 1,25(OH)2D3 in the treatment of psoriasis vulgaris. In addition to 1,25(OH)2D3, the synthetic vitamin D3 analogues 1 alpha(OH)D3, 1,24(OH)2D3, and calcipotriol have undergone clinical evaluation. Calcipotriol has been studied most extensively. Compared with 1,25(OH)2D3, calcipotriol is about 200 times less potent in its effects on calcium metabolism, although similar in receptor affinity. In double-blind, placebo-controlled, randomized studies, topical calcipotriol (50 micrograms/gm, up to 100 gm weekly) has been shown to be efficacious and safe for the treatment of psoriasis. A similar therapeutic profile has been seen in long-term studies. In comparative studies topical calcipotriol is slightly more efficacious than betamethasone 17-valerate and dithranol. The mode of action of calcipotriol and other vitamin D3 analogues in psoriasis is not known. Although vitamin D3 analogues affect epidermal growth, their immunosuppressive properties may be equally important for their antipsoriatic effect.