EFFICACY, TOLERABILITY, AND SAFETY OF CALCIPOTRIOL OINTMENT IN DISORDERS OF KERATINIZATION - RESULTS OF A RANDOMIZED, DOUBLE-BLIND, VEHICLE-CONTROLLED, RIGHT-LEFT COMPARATIVE-STUDY

Background and Design: Disorders of keratinization are a heterogeneous group of diseases that have in common a defect in cornification. The bioactive form of vitamin D-3 has been shown to modulate epidermal proliferation and differentiation. The purpose of the present study was to determine the effect of the synthetic vitamin D-3 calcipotriol in a randomized, double-blind, placebo-controlled, right/left comparative study. The 67 patients included in the study were at least 12 years of age and had the following diseases: ichthyosis vulgaris (n=9), X-linked ichthyosis (n=8), congenital ichthyosis (n=10), hereditary palmoplantar keratoderma (n=20), keratosis pilaris (n=9), and Darier's disease (n=11). Calcipotriol ointment (SO mu g/g) and placebo (vehicle of calcipotriol ointment) were applied to all patients twice daily for up to 12 weeks. The patients were allowed to use up to 120 g of calcipotriol ointment per week. Results: At the end of the treatment regimen, calcipotriol ointment had an effect on the improvement of the ichthyoses, although to a variable degree. No therapeutic effect was detected in palmoplantar keratoderma or keratosis pilaris. Eight of 12 patients with Darier's disease had to be withdrawn because of skin irritation or a worsening of the disease. Skin irritation occurred in 18 cases (26%) only on the calcipotriol-treated side, and in one case (1%) only on the placebo-treated side. Nine cases (13%) had irritation on both sides. The amount of calcipotriol ointment used per week was lowest in palmoplantar keratoderma (mean, 11.8 g/wk; range, 2.1 to 25.6 g/wk) and highest in congenital ichthyosis (mean, 59.3 g/wk; range, 11.4 to 94.7 g/wk). There was no clinically significant change of serum calcium levels during the treatment period. Conclusion: Short-term treatment with calcipotriol ointment (50 mu g/g) used in amounts up to about 100 g/wk is moderately efficacious, well-tolerated, and safe in adult patients with various ichthyoses.