Sequential Therapy Is Way to Go in Psoriasis : After the combo achieves good control, the plan should downshift, eliminating the more toxic agent.

NEW ORLEANS — Sequential therapy is a great way to get quick, effective control of chronic psoriasis while keeping costs down and minimizing the patient's exposure to potentially toxic systemic agents, John Koo, M.D., said at the annual meeting of the American Academy of Dermatology.

“You can start with a fast-acting agent like cyclosporine, then add a biologic and try to taper the cyclosporine,” said Dr. Koo of the University of California, San Francisco. It's important to maintain the initial systemic treatment for at least 3 months, he stressed, because any biologic will take that long to kick in.

“It's not a good idea to stop the prebiologic agent when starting the biologic because the biologic takes at least 3 months to build efficacy and the prebiologic's efficacy will fade within 1 month,” setting the stage for a flare, Dr. Koo said.

After the combination achieves good control, the plan should downshift, eliminating the more toxic systemic agent in favor of some form of maintenance therapy. This could be the biologic alone (with the temporary addition of a systemic if flare occurs), a biologic plus UVB or oral retinoid, or another safe and effective long-term regimen.

Unfortunately, some older therapies are falling by the wayside as the heavily promoted biologics take center stage. But focusing so heavily on these new drugs shortchanges patients who need access to the entire arsenal of treatment. “For optimal care, these patients need the full range, whether it's being promoted or not. PUVA isn't heavily promoted anymore, but it still works,” he said.

When one looks at overall efficacy, “biologics are in the less effective range. They aren't always adequate as monotherapy, even with optimized topical therapy, especially if the patient is large or if it's during the winter,” Dr. Koo said.

As a rough comparison of effectiveness, he said, retinoid plus psoralen and UVA will effect an improvement of 75% in the Psoriasis Area and Severity Index (PASI 75) in 100% of patients by 3 months. This is slightly better than the best biologic, infliximab (PASI 75 in about 90% by 3 months), but it's a lot cheaper and doesn't carry infliximab's risk of infection. The other biologics fall far behind this efficacy level: PASI 75 improvement by 3 months in 21% for alefacept, 28% for efalizumab, 34% for etanercept 25 mg biweekly, and 49% for etanercept 50 mg biweekly.

In contrast, PASI 75 by 3 months is seen in about 90% of patients on PUVA plus calcipotriene; 80% of those on moderate-dose cyclosporine; 71% of those on PUVA alone; 60% of those on methotrexate; and 55% of those on narrowband UVB phototherapy. The downside of these older treatments is that they're not as convenient as simply taking a pill, Dr. Koo said. They involve multiple office visits, which can be a problem in areas of limited medical access, or with noncompliant patients. And some carry a risk of organ damage.

This risk is one reason why some have shunned older systemic agents and embraced the biologics, Dr. Koo noted. “A third of U.S. dermatologists don't feel comfortable prescribing methotrexate or cyclosporine. Another third will only use them when 'pushed to the wall.' The remaining third account for more than 95% of all prebiologic systemic therapy prescribed in the United States.”

Cost should be another consideration, Dr. Koo said. The biologics are considerably more expensive than prebiologic treatments. Approximate annual cost of alefacept approaches $20,000; infliximab, $18,000; and etanercept, $17,000. In contrast, a year of cyclosporine runs about $10,000; acitretin, $5,000; PUVA and UVB, about $2,500; and methotrexate, about $1,500.