Combination therapy offers new opportunities

"Currently, the calcipotriene/beta-methasone preparation is available and being widely prescribed in a number of countries outside of the United States. With hope that Food and Drug Administration (FDA) approval for this fixed combination product may be granted in 2006, it is important for practitioners to begin acquainting themselves with how it can be used," says Dr. Koo, professor and vice chairman, department of dermatology, University of California, San Francisco.

Sequential therapy with calcipotriene

However, that distinction reflects its versatility for use in combination therapy and sequential therapy rather than its efficacy as a monotherapy agent.

"There are good, evidence-based studies demonstrating that the addition of calcipotriene to a wide variety of other psoriasis therapies, including tazarotene, topical corticosteroids, methotrexate, cyclosporine, acitretin, UVB and PUVA, results in improved outcomes relative to monotherapy with either agent alone," Dr. Koo observes.

Among those agents, however, calcipotriene is most often combined with a superpotent topical corticosteroid in a three-step, sequential regimen.

Once combination calcipotriene/ betamethasone becomes available in the United States, topical sequential therapy is one treatment scenario where the combination product fits in, Dr. Koo says.

Results of a study by Mark Lebwohl, M.D., and colleagues published almost a decade ago demonstrated potent synergy between calcipotriene and halobetasol propionate 0.05 percent ointment (Ultravate, Westwood Squibb). In that trial, patients who used calcipotriene in the morning and halobetasol at night achieved faster and more complete clearing than controls using either agent alone twice daily.

"It is important for clinicians to recognize that based on available evidence from well-designed clinical trials, the combination of calcipotriene with a superpotent topical steroid is the most effective topical regimen that can be offered to a patient with localized psoriasis," Dr. Koo says.

Maximizing efficacy, safety

The sequential regimen for using calcipotriene plus the corticosteroid is designed to fulfill the goals of achieving rapid and sustained clearing while limiting the duration of use of the ultrapotent topical corticosteroid for safety reasons.

In that approach, treatment begins with the "quick fix" phase in which each agent is either used once daily, one in the morning and the other at night, or both are used twice daily by freshly mixing equal quantities of each together in the palms of the hands.

Step two, the "transition" phase, is initiated once the psoriasis has been brought under control. In it, corticosteroid treatment is stepped down from daily to weekends only, with calcipotriene used twice daily on weekdays only.

"In the transition phase, the ultrapotent corticosteroid is tapered to avoid rebound while the calcipotriene is continued as a steroid-sparing agent to maintain disease control," Dr. Koo says.

In step three, the "maintenance" phase, patients continue treatment with twice-daily calcipotriene. This phase can begin once the psoriasis plaque has become pink and perfectly flat, and it is continued until the lesion disappears.

New option for sequential therapy

Dr. Koo says the fixed combination of calcipotriene/betamethasone dipropionate will offer new versatility in approaches to sequential therapy.

Studies working with calcipotriene/ betamethasone dipropionate show it was more effective than either of its components used alone, and notably, efficacy was generally similar whether it was used once daily or twice a day.