Biologics' efficacy data growing

September 1, 2005

Chicago — Among the more promising directions among biologic drugs for psoriasis are longer treatment regimens and combinations with other modalities, says Mark Lebwohl, M.D., professor and chairman, department of dermatology, Mount Sinai School of Medicine, New York.

Chicago - Among the more promising directions among biologic drugs for psoriasis are longer treatment regimens and combinations with other modalities, says Mark Lebwohl, M.D., professor and chairman, department of dermatology, Mount Sinai School of Medicine, New York.

"One of the problems with alefacept (Amevive, Biogen Idec) has been that it's very slow acting, and the response rate has been disappointing. Only about a third of patients get dramatically better," Dr. Lebwohl says.

In a double-blinded study recently performed at Mount Sinai, researchers treated patients with a total of 16 weekly alefacept injections or with 12 weeks of alefacept plus four weeks of placebo.

At six months, he says, "The average improvement in PASI score was approaching 60 percent. In the group that received only 12 weeks of treatment, there was not an upward trajectory. Improvement was actually beginning to taper off, and it was only in the mid-30 percent range."

Another recent study pitted alefacept monotherapy (12 weekly injections) against the combination of alefacept and six or 12 weeks of broadband UVB therapy.

Combined therapies

"The interesting thing is that it usually takes at least 12 weeks for patients to dramatically improve," Dr. Lebwohl says. "But what this study showed was that by combining the two therapies, there's a much more rapid improvement than with alefacept alone. Usually six weeks of broadband UVB was not enough to achieve and sustain an improvement in psoriasis, but when combined with alefacept, at six months post-treatment, patients on average still had a nearly 70 percent improvement in PASI scores (Koo J, unpublished data).

A similar study involving methotrexate with either alefacept or placebo for treating psoriatic arthritis showed a statistically significant benefit in psoriatic arthritis severity scores for the group receiving alefacept and methotrexate, Dr. Lebwohl reports.

"It does appear that alefacept benefits psoriatic arthritis - 54 percent of patients in the combination group achieved ACR 20 compared to 23 percent in the placebo group," he says.

Regarding efalizumab (Raptiva, Genentech), Dr. Lebwohl says, "One of the things that might be disappointing if one stops treatment early is that many patients don't respond by 12 weeks. But if one keeps on going, patients who do respond continue to respond, and there's a greater response rate as time goes on."

Weight

Patients' weight appears unrelated to the efficacy of efalizumab, according to Dr. Lebwohl. He recently presented a study involving efalizumab and obese psoriasis patients.

Dr. Lebwohl says, "It showed that when one breaks down the response of the patients who weighed over 100 kg versus those who weighed under 100 kg, the patients over 100 kg do just as well as the lighter ones (Lebwohl M. Poster presentation. American Academy of Dermatology's Academy '05, July 20-24, 2005, Chicago). That's important because in general, treating obese patients with psoriasis has been more difficult.

"Most of the other biologic drugs are fixed-dose. Regardless of weight, alefacept is 15 mg weekly; etanercept (Enbrel, Amgen/Wyeth) is 50 mg once or twice a week; infliximab (Remicade, Centocor), which is not yet approved for psoriasis, uses a variable dose. But efalizumab represents a drug that is approved for psoriasis that is variable dose, given in mg per kg. So the bigger a patient is, the more the patient gets. Infliximab furthermore is given by IV infusion," while patients can inject efalizumab themselves, he says.

As for etanercept, a two-year study compared results achieved by patients receiving this drug and by patients who received a placebo for either six or 12 months before beginning etanercept therapy.