Topical combination therapies for psoriasis offer high degree of efficacy, safety

Key Points

"Combination therapy in psoriasis is absolutely the standard of care," says Dr. Pariser, professor of dermatology, Eastern Virginia Medical School, and a Norfolk, Va., dermatologist in private practice. "Virtually all patients with psoriasis are treated with combination therapy. If they're on systemic agents, there will often be a few spots that don't respond as well. Therefore, topical therapies are important for virtually everyone who has psoriasis," no matter how mild or serious their disease.

"Topical corticosteroids in one form or another, usually the more potent ones, are the most commonly prescribed topical agent for psoriasis," he says. In addition, "There's a lot of interesting data on combination therapy using vitamin D topically, along with topical steroids."

A recent meta-analysis of 50 randomized, controlled trials analyzed combination psoriasis treatments in comparison to monotherapies. When researchers stratified results by corticosteroid class, Dr. Pariser says, "They concluded that by adding a corticosteroid to a calcipotriene regimen, the likelihood of disease clearance increased by 28 percent for a Class 1 corticosteroid (95 percent confidence interval/CI: 16 to 41 percent) and 14 percent for a Class 2 steroid (95 percent CI: 5 to 22 percent; Bailey EE, Ference EH, Alikhan A, et al. Arch Dermatol. 2011 Dec 19. [Epub ahead of print])." Compared to vitamin D derivative monotherapy, combining vitamin D with corticosteroids conferred a 22 percent higher likelihood of clearance, he says.

"That's a significant finding that supports the notion that we've all had clinically over many years that adding the corticosteroid to the vitamin D does make it work better, and over time can actually achieve clearance" in the percentages specified above, Dr. Pariser says.

In two studies that contained sufficient data to analyze efficacy in terms of reductions in disease severity scores, investigators found that combination therapy with any corticosteroid class decreased disease severity by 1.52 units of standard deviation (95 percent CI: -2.56 to -0.48) versus vitamin D derivative monotherapy.

Conversely, in the same meta-analysis, if patients used a Class 3 or weaker steroid in combination with topical vitamin D, it did not improve disease clearance compared with vitamin D derivative monotherapy, says Mark Lebwohl, M.D.

Product update

Combination products available in the United States include a fixed combination of betamethasone dipropionate and calcipotriene, Dr. Pariser says. In a four-week study, the combination product worked better than either of its ingredients used separately, or its vehicle (Kaufmann R, Bibby AJ, Bissonnette R, et al. Dermatology. 2002;205(4):389-393).

In this study, investigators randomized 1,603 patients to one of four double-blinded treatments: once-daily combination ointment, betamethasone dipropionate ointment, calcipotriol (known as calcipotriene in the United States) ointment, or the ointment vehicle.

When treatment ended, mean percentage improvements in Psoriasis Area and Severity Index (PASI) scores were 71.3 percent, 57.2 percent, 46.1 percent and 22.7 percent, respectively. Additionally, investigators concluded that the combination treatment was well tolerated: 6 percent of patients who used it experienced local adverse reactions, versus 4.9 percent of betamethasone dipropionate users, 11.4 percent of calcipotriol users and 13.6 percent of vehicle users.

Patients also can accomplish combination regimens by purchasing topical steroid and topical vitamin D products separately, or having the combination compounded a compounding pharmacy, Dr. Pariser says.