Combination Approaches Using Topical Vitamin D for Psoriasis

Clinical Focus: psoriasis

Combination Approaches Using Topical Vitamin D for Psoriasis A combination of topical vitamin D with some form of phototherapy and/or systemic therapy is a safe and effective option for plaque psoriasis.

By Jerry Bagel, MD

soriasis is a complex disease and therefore the use of combination therapy to optimize benefits and Several studies have evaluated the minimize risk is intuitive. With the right combina- potential benefits of differing tion, the effect of each individual component can variations of topical vitamin D Pbe maximized for optimal response. While topical therapy often forms the foundation of any combination, any num- analogues with phototherapy and ber of possibilities involving oral, systemic, and even light- systemic therapy separately and based options in conjunction with topical therapy may together. constitute an effective approach for plaque psoriasis. One particular emerging option combines topical vitamin D with phototherapy and systemic therapy. UVB radiation than did the side to which petrolatum had Several studies have evaluated the potential benefits been applied. of differing variations of topical vitamin D analogues Another study evaluated 101 patients who received with phototherapy and systemic therapy separately and broadband UVB plus calcipotriol BID on one side of the together. These studies may point to new directions in body and on the other side received no UVB and only cal- treatment. This article will review these studies and explore cipotriol BID.2 The investigators found that 57 percent of further how this specific combination might be beneficial patients were clear in the calcipotriol plus UVB group, as for patients. opposed to just 25 percent of patients in the calcipotriol- alone group. Reviewing the Data Narrowband-UVB (NB-UVB) can also yield effective Vitamin D Plus Phototherapy. An eight-week study evalu- results in combination with calcipotriol. One study evaluated calcitriol 3ug/g ointment in combination with broad- ated 50 patients, all of whom received NB-UVB treat- band UVB; 104 patients with a Body Surface Area (BSA) ment.3 In addition, 25 patients received calcipotriol BID greater than or equal to 25 percent received UVB treat- and 25 patients were given emollient BID. By the 14th ments on their entire body.1 Patients were also treated treatment, those in the calcipotriol group decreased by with white petrolatum on one half of the body and the 75 percent in PASI, as compared to 55 percent in the other half with calcitriol ointment. In the calcitriol-treated emollient group. Additionally, only 18 treatments were patients, 45 percent cleared with a 65 percent improve- necessary in the calcipitriol group, as opposed to 20 in the ment in PASI, whereas in the petrolatum side only 20 emollient group. percent cleared with a 43 percent improvement in PASI. In Psoralen plus UVA (PUVA) can also be combined effec- addition, the calcitriol-treated side required 34 percent less tively with topical vitamin D. A 10-week study in 2004

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evaluated calcipotriene cream and PUVA in 120 patients with a BSA greater than or equal to 30 percent.4 Findings Topical vitamin D can have an anti- showeddept that 87 percent of patients headline receiving PUVA three inflammatory and anti-proliferative times per week plus calcipotriene achieved PASI 90, with a UVA dose of 99, as compared to just 47 percent of effects. Moreover, data suggest it patients receiving PUVA plus placebo cream achieving may provide an additive benefit to PASI 90 with a UVA dose of 120. the effects of phototherapy and Frappaz evaluated 110 patients combining PUVA with calcipotriol.dept5 deckThe study involved a two-week washout peri- systemic agents. od. During the second two weeks, patients were randomized todept receive byline calcipotriol ointment or placebo. Then, in the third phase of the study, patients underwent 10 weeks Commentary of PUVA plus either calcipotriol or placebo. Patients in the Psoriasis is a multi-factorial disease with various gene calcipotriol group saw a PASI improvement of 91 percent, activities and different mechanisms controlling them. as textopposed to 75 percent improvement for patients with Vitamin D can be beneficial because it has immunomodu- placebo. Moreover, 87 percent of patients in the calcipot- latory properties that decrease anti-microbial peptides riol group achieved PASI 75, as compared to 64 percent of seen in keratinocytes that promote the inflammatory pro- those in the placebo group. cess. Vitamin D is also involved in normal keratinization Systemic Treatments Plus Vitamin D. Topical vitamin and can decrease the proliferative rate in the epidermis. D and systemic combinations for psoriasis date back as Therefore, the benefit of topical vitamin D is two-fold: it early as 1994, when Grossman evaluated 69 patients over can have both an anti-inflammatory and an anti-prolifer- a six-week period comparing cyclosporine plus topical cal- ative effect. Moreover, data suggest that it may provide cipitriol versus cyclosporine and placebo.6 Results showed an additive benefit to the effects of phototherapy and that 50 percent of patients receiving the cyclosporine systemic agents. In addition, by using topical vitamin D plus calcipotriol combination achieved PASI 90, with total in combination with these other therapies, clinicians can improvement of 81 percent, as compared with just 12 decrease the doses of either the light or systemic agent. In percent of patients in the cyclosporine/placebo ointment doing so, you can reduce the toxicity associated with the group achieving PASI 90, and an overall improvement of use of these agents as monotherapies. Thus, the poten- 58 percent. tial benefits of a combination using topical vitamin D as Calcipotriol has also been used in combination with a foundation can increase the efficacy and safety of all acitretin. For example, Kerhof evaluated the effect of adding therapies. n calcipitriol ointment to acitretin therapy in a 12-week study.7 All patients started on acetretin 20mg qd Dr. Bagel has served as consultant, researcher, and were adjusted up to 70mg. Some patients then received or speaker for Amgen, LEO, Abbott, Janssen, calcipotriol, whereas others received a vehicle ointment. In Galderma, and GlaxoSmithKline. the acitretin plus calcipotriol group, 67 percent of patients Jerry Bagel, MD, FAAD, is director of the Psoriasis were fully clear, with a total of 73 percent improvement in Treatment Center of Central New Jersey. PASI; total acitretin used was 1680mg. In the acitretin plus placebo group, 40 percent of patients were clear at the end 1. Ring J, Kowalzick L, Christophers E, et al. Calcitriol 3 microg g-1 ointment in combination with ultraviolet B phototherapy for the treatment of plaque psoriasis: results of a comparative study. Br J Dermatol. 2001;144(3):495-9. of the study, with a total of 45 percent improvement in 2. Molin L. Topical calcipotriol combined with phototherapy for psoriasis. The results of two randomized trials and a review PASI; total acitretin used was 2100mg. of the literature. Dermatology. 1999;198(4):375-81. Another possible systemic combination methotrexate 3. Woo WK, McKenna KE. Combination TL01 ultraviolet B phototherapy and topical calcipotriol for psoriasis: a prospective (MTX) along with topical vitamin D. One study evaluated randomized placebo-controlled clinical trial. Br J Dermatol. 2003;149(1):146-50. 4. Torras H, Aliaga A, Lopez-Estebaranz JL, et al. A combination therapy of calcipotriol cream and PUVA reduces the UVA MTX-treated patients given either calcipotriol or placebo dose and improves the response of psoriasis vulgaris. J Dermatolog Treat. 2004;15(2):98-103. ointment after cessation of MTX.8 At the time of relapse, 5. Frappaz A, Thivolet J. Calcipotriol in combination with PUVA: a randomized double blind placebo study in severe MTX was resumed at 50 percent of the initial dose. No psoriasis. Eur J Dermatol. 1993;3:351-4. 6. Grossman RM, Thivolet J, Claudy A, et al. A novel therapeutic approach to psoriasis with combination calcipotriol flares were reported in the calcipotriol group for 113 days, ointment and very low-dose cyclosporine: results of a multicenter placebo-controlled study. J Am Acad Dermatol. as compared to just 35 days to flare in the placebo group. 1994;31(1):68-74. The amount of MTX needed for improvement in the cal- 7. van de Kerkhof PC, Cambazard F, Hutchinson PE, et al. The effect of addition of calcipotriol ointment (50 micrograms/g) to acitretin therapy in psoriasis. Br J Dermatol. 1998;138(1):84-9. cipotriol group was 6.5mg, as compared to 9.9mg in the 8. de Jong EM, Mørk NJ, Seijger MM, et al. The combination of calcipotriol and methotrexate compared with methotrexate placebo group. and vehicle in psoriasis: results of a multicentre placebo-controlled randomized trial. Br J Dermatol. 2003;148(2):318-25.

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