Efficacy and safety of topical calcitriol 3 [micro]g/g ointment, a new topical therapy for chronic plaque psoriasis
Journal of Drugs in Dermatology, August, 2009 by Leon Kircik
ABSTRACT
Topical vitamin D modulators are among the most widely used medications for the treatment of psoriasis. Calcitriol, the naturally occurring active form of vitamin [D.sub.3], has long been used for topical psoriasis therapy in Europe and other parts of the world and was recently approved in the United States. Calcitriol 3 [micro]g/g ointment has been extensively evaluated for the treatment of chronic plaque-type psoriasis and has been shown to be effective, safe and well-tolerated in a number of short-term and long-term clinical trials. Pharmacokinetic studies in patients with psoriasis and healthy control subjects have demonstrated that topical calcitriol ointment produces little systemic absorption of calcitriol and does not alter systemic calcium homeostasis significantly even when applied to approximately one third of the body surface area. Calcitriol ointment is associated with a low rate of cutaneous irritation and does not increase the sensitivity of treated skin to phototoxicity following treatment with ultraviolet treatment. In two randomized, double-blind clinical trials, twice-daily application of calcitriol ointment for eight weeks resulted in clearing or minimal residual psoriasis in approximately 34% of patients, compared with 12% to 22.5% of patients treated with vehicle ointment (P = 0.005 in study 1 and P
INTRODUCTION
As described in an accompanying article (see The Role of Topical Vitamin [D.sub.3] Receptor Modulators in Psoriasis Therapy by Emil A. Tanghetti, MD, pages4), topical vitamin [D.sub.3] psoriasis remedy therapy is among the most widely used approaches to the treatment of psoriasis. A 12-year survey (ending in 2001) of prescribing patterns among office-based physicians (dermatologists and nondermatologists) in the United States (U.S.) found that although corticosteroids are the most commonly used class of medications for psoriasis, the synthetic vitamin [D.sub.3] analog calcipotriene was the single most frequently listed psoriasis medication. (1) Calcipotriene monotherapy has been shown to substantially improve symptoms in approximately 60-70% of patients with chronic plaque psoriasis, reaching its maximum effectiveness after approximately six-to-eight weeks. (2) However, calcipotriene is associated with substantial cutaneous irritation in approximately 20% of patients and is not suitable for application to the face. (3) A second synthetic vitamin [D.sub.3] analog, tacalcitol, is also approved for use in some countries outside the U.S. Tacalcitol is less likely than calcipotriene to produce cutaneous irritation but may also be less effective.(3), (4) There is, therefore, a need for new topical vitamin [D.sub.3] therapies that produce high treatment response rates without causing cutaneous irritation.
The vitamin [D.sub.3] modulator calcitriol (1[alpha], 25-dihydroxyvitamin [D.sub.3]), long available in an ointment formulation for the treatment of psoriasis in Europe, is now the only vitamin [D.sub.3] ointment available for use in the U.S. In contrast to synthetic vitamin D products such as calcipotriene, calcitriol is a naturally occurring active form of vitamin D that is an important regulator of normal calcium homeostasis. (5) Although the precise mechanism by which calcitriol improves psoriasis is not completely understood, calcitriol suppresses several physiologic processes that are thought to contribute to the pathogenesis of psoriasis. For example, vitamin [D.sub.3] products have been shown to inhibit keratinocyte proliferation, to promote keratinocyte differentiation, and to decrease the expression of a broad range of proinflammatory cytokines that stimulate T-cell proliferation and cutaneous inflammation. (2), (5)
Calcitriol has been extensively evaluated for the treatment of psoriasis in a number of patient populations and treatment regimens. Calcitriol 3 [micro]g/g topical ointment has been shown to improve the symptoms of psoriasis, with a sustained long-term maintenance of benefit and a low incidence of adverse effects, without clinically altering systemic calcium metabolism