Biologic data growing

Las Vegas

- As new biologic drugs navigate through the FDA approval process, the amount of efficacy data - including comparative studies - available to dermatologists is growing, says a leading psoriasis clinician and researcher.

"One of the things it's fascinating in the world of research is, why don’t we more frequently see head-to-head studies?" says Alexandra Boer Kimball, M.D., M.P.H., director of the Clinical Unit for Research Trials in Skin (CURTIS), Harvard Medical School.

A major reason is that due to the necessary sample sizes and expenses, such studies prove prohibitive, she says. Furthermore, the FDA requires only comparisons to placebos.

However, one new psoriasis drug that is undergoing comparative research is ustekinumab (Centocor), a novel IL-12/23 antibody, which Dr. Kimball predicts is likely to be available in the United States around January 2009. A phase 3, multicenter randomized blinded study (the ACCEPT study) pits etanercept with a 50 mg biweekly (loading) dose against two dosages of ustekinumab: 45 and 90 mg given at weeks zero, four and 12.

Initial efficacy data shows that at 12 weeks, etanercept achieved PASI 75 response in 57 percent of patients, versus 68 and 74 percent for ustekinumab at the 45 and 90 mg doses, respectively, Dr. Kimball tells Dermatology Times.

In terms of PASI 90, however, the ustekinumab doses achieved response rates of 36 and 45 percent, respectively, versus 23 percent for etanercept.

Regarding predictors of treatment success, she says, "Patients who had not taken previous biologics tended to do better by about 10 to 15 percent than those who had."

So, if a patient already has tried a biologic drug before ustekinumab, "You may want to temper their expectations about how they'll respond."

In a phase 2 study of ABT-74 (Abbott), researchers took patients who had responded with PASI 75 after 12 weeks of therapy off medication until they reverted to PASI 50, Dr. Kimball says.

Then, investigators put them back in their original doses. "What was striking about this data is that after a single dose, 63 percent of patients had PASI 75 response at week 12," while four alternate dosing schedules achieved PASI 75 in around 90 percent of patients.

However, Dr. Kimball says, "Ustekinumab doesn't have a long half-life."

Fortunately, many patients who lost their PASI 75 response while off treatment responded at a similar level after resuming treatment, she says. DT

Disclosure: Dr. Kimball is an investigator and consultant for Abbott and Centocor, an investigator for Pfizer and has received fellowship funding from Centocor.