Offer systemic therapy as first-line defense

Dr. Menter discussed optimization of alefacept therapy for psoriasis at the XXIV Annual Meeting of the Latin American Dermatologists (RADLA) in Buenos Aires in May.

"It is time that all of us recognize the systemic manifestations of psoriasis and the impact it has on quality of life," Dr. Menter says. "Psoriasis is a disease that is underrated all over the world. As dermatologists, we need to understand the significance of improving the quality of life of our patients over the long term."

Psoriasis affects from 4.5 to 7 million people in the U.S., with between 150,000 and 260,000 new cases each year.

Roughly half a million patients have moderate to severe psoriasis. Although systemic therapy options now include three biologics, in addition to the traditional systemic agents such as methotrexate, data from 2004 indicate that fewer than 150,000 patients are on systemic therapy. Less than 50 percent of patients with active disease are not currently being treated for moderate to severe psoriasis.

Treatment paradigms

In the traditional paradigm, as disease severity increases, treatment progresses from OTC products such as emollients and creams, to prescription drugs such as topical steroids, vitamin D analogs and topical retinoids, and then perhaps to phototherapy using UVB broadband, UVB narrowband, or PUVA.

With severe disease, systemic therapies, such as cyclosporine and methotrexate, are prescribed. As the potency of the treatment increases, progressing from OTC products to systemic therapies, the risks of potential side effects also increase.

Patients with severe psoriasis should be offered systemic therapy as initial therapy.

The Dallas experience

As of April, 2005, 755 patients with moderate to severe psoriasis were receiving treatment with systemic therapy at Dr. Menter's clinic in Dallas.

Of these, 423 patients were on one of the new biologic therapies, and 332 patients were on traditional systemic therapies. Dr. Menter reported his clinic's experience with transitioning psoriatic patients from other systemic therapies to alefacept (Amevive, Biogen). The goal in the transition period is to maintain disease stability without rebound or relapse.

In transitioning patients to alefacept, expect a slow initial response, advises Dr. Menter. Gradually tapering the methotrexate or cyclosporine A dose with a "step-down" reduction over the first six to 10 weeks of alefacept therapy appears to be a safe and effective strategy.

In Dr. Menter's clinic, transition from methotrexate to alefacept has been initiated in 42 patients whose psoriasis was effectively controlled by methotrexate. Approximately two-thirds of these patients were receiving more than 15 mg of methotrexate per week.

Adverse event profile

The adverse event profile seen in patients transitioning from methotrexate to alefacept was similar to that seen in patients using either drug as monotherapy.

As expected, CD4+ cell counts in some patients transitioning to alefacept decreased following initiation of alefacept therapy. During the transition to alefacept, the median low CD4+ cell count was 408 cells per microliter (range: 176 to >1000 cells per microliter). Four patients had CD4+ cell counts below 250 cells per microliter. For three of these patients, alefacept therapy was withheld for one to three weeks until the CD4+ cell count increased. The fourth patient discontinued alefacept therapy after persistently low CD4+ cell counts, and subsequently recovered.

Dr. Menter reports similar outcomes in transitioning psoriatic patients from cyclosporine A to alefacept in his clinic.

Combination therapy

"Preliminary data suggest that alefacept can be effectively and safely administered with traditional psoriasis therapies," Dr. Menter says.