Promising outlook: Study shows efalizumab provides long-term hope for disease-free intervals

Jul 01, 2008, 4:00am

The results of a three-year study with efalizumab show that patients with moderate-to-severe psoriasis are able to maintain high PASI scores, reflecting long-term hope for disease-free intervals.

Key Points

National report - Therapies for plaque psoriasis abound, but every dermatologist knows that, because of the nature of psoriasis, the long-term effectiveness of a therapy is what matters the most.

The results of a recent study with efalizumab (Raptiva, Genentech) demonstrate that long-term results are achievable and can be maintained for at least three years.

"This is, to date, the longest continuous dosing trial using biologic therapy for psoriasis. Efalizumab is known to be effective for psoriasis, but we wanted to follow the long-term results, hoping not to see a wavering of drug effect and a resurgence of symptoms after a year or so, as seen with other biologics," says Craig Leonardi, M.D., clinical professor of dermatology, St. Louis University, St. Louis, Mo., and lead investigator of the study.

The multicenter phase 3 clinical study included 339 patients with moderate-to-severe chronic plaque psoriasis.

In the initial three months of the trial, patients received subcutaneous efalizumab 2 mg/kg once a week or placebo. In the third month, patients were randomized to concomitantly receive either fluocinolone acetonide 0.01 percent or placebo ointment.

Patients who achieved at least Psoriasis Area and Severity Index (PASI) 50 were then eligible to receive efalizumab 1 mg/kg once weekly for up to 33 months until the end of the trial.

Results showed that at three months, 41.3 percent and 13 percent of patients achieved at least a 75 percent (PASI 75) and 90 percent (PASI 90) improvement of their symptoms, respectively.

At three years, PASI 75 and PASI 90 were seen in 45.4 percent and 24.5 percent of patients, respectively.

Results

"What is unusual about these results is that the efficacy of efalizumab was steadily maintained across 36 months. The reason for this long-term efficacy however, remains unclear.

"Interestingly, this remarkable achievement is not seen with other biologics, such as etanercept (Enbrel, Amgen), adalimumab (Humira, Abbott) and infliximab (Remicade, Centocor), as these biologics demonstrate a decay of drug effectiveness over time.

"Though the efficacy may initially be better with some of these drugs, the loss of response over time can be a problem for the patients and their dermatologists," Dr. Leonardi tells Dermatology Times.

Many dermatologists who prescribe efalizumab to their patients believe that if a patient gets through the first six to eight months of the drug, he or she will do very well in the long term, which is reflected in these study results.

According to Dr. Leonardi, efalizumab has a solid place in the grand scheme of psoriasis therapy and has earned its place next to the TNF antagonists, such as etanercept, adalimumab and infliximab.

"If you have patients who seem to be unresponsive to TNF blockade, efalizumab is a very rational drug to go to. The research data shows us that the response seems to be maintained over time, and I do believe that if you get through the first six to eight months of this drug and the patient is doing very well, this effect will continue in the long term.

"Currently, I have many patients who have been receiving efalizumab for the past six-and-a-half years, and they are all doing great," Dr. Leonardi says.

Safety profile

The safety profile seen with efalizumab in this study was good, with no new and no increase of adverse events seen.

Dr. Leonardi says malignancy occurrences did not increase over the three-year study period, and patients seemed to be stable.

He says that the flare occurrences seen throughout the course of this trial remained low and did not increase over three years.

Overall, this study "gives us a lot of confidence in using this drug for the long term in patients with moderate-to severe chronic plaque psoriasis," Dr. Leonardi says.