Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris

MC 903 is a novel vitamin D analogue which has been tested for its effects on cell differentiation and cell proliferation in vitro using the human histiocytic lymphoma cell line U937, and on calcium metabolism in rats in vivo. In the present investigation MC 903 was compared to the natural metabolite of vitamin D3, 1 alpha,25-dihydroxycholecalciferol [1,25(OH)2D3] and to its synthetic analogue 1 alpha-hydroxycholecalciferol [1 alpha (OH)D3]. MC 903 was found to be a potent inducer of cell differentiation and to inhibit cell proliferation and DNA-synthesis in concentrations comparable to those observed with 1,25(OH)2D3. 1 alpha (OH)D3, which is only active after metabolic conversion to 1,25(OH)2D3, was more than 100 times less potent. Oral or intraperitoneal administration of MC 903 to rats showed that the compound was at least 100 times less active than 1,25(OH)2D3 and 1 alpha (OH)D3 in causing hypercalciuria, hypercalcemia and bone calcium mobilisation. The low vitamin D activity of MC 903 was further confirmed by administration of the compound to rachitic rats. The strong direct effects of MC 903 on cell proliferation and cell differentiation, coupled with its decreased activity as a classical vitamin D makes this compound an interesting candidate for studies in human proliferative disorders such as psoriasis.

Calcipotriol (the synthetic compound MC 903) is a structural analogue of naturally occurring, biologically active calcitriol. Calcipotriol and calcitriol (1,25-dihydroxy vitamin D3) show similar receptor binding and comparable effects on cell differentiation. However, calcipotriol seems to be at least 100 times less potent in its effects on calcium metabolism. In a double-masked study involving 50 patients with psoriasis vulgaris, the efficacy and tolerability of ointments containing various calcipotriol concentrations (25, 50, or 100 micrograms/g) or the vehicle alone were compared in a study involving a right-left, within-patient randomized design. Patients were treated twice daily for 8 weeks. Marked improvement was seen in 40% of the patients treated with the 25-micrograms/g concentration of calcipotriol in 63% of patients treated with the 50-micrograms/g concentration, and in 88% treated with the 100-micrograms/g concentration. No patient treated with placebo had more than slight improvement. Five patients developed facial dermatitis during the study. The serum levels of ionized calcium were unchanged. This study demonstrates that calcipotriol ointment provides an effective and well-tolerated treatment of psoriasis vulgaris.