Updates on psoriasis

February 1, 2006

While these psoriasis treatment options are exciting, Dr. Lebwohl admits that dermatologists do not yet have a drug option for psoriasis that is hands-down superior to cyclosporine.

The intravenous infusion drug and injectable protein adalimumab work to block the inflammatory effects of tumor necrosis factor alpha (TNF-alpha).

"They both also work very well for psoriasis," Mark Lebwohl, M.D., dermatologist, professor and chairman, department of dermatology at the Mount Sinai School of Medicine, New York City, tells Dermatology Times.

Studies have shown that nearly 90 percent of psoriasis patients achieve Psoriasis Area and Severity Index (PASI) score reductions of 75 percent or more with infliximab. With high-dose adalimumab, about 80 percent achieve PASI 75. A high dose of adalimumab is 40 mg of the drug every week, versus every other week, according to Dr. Lebwohl.

Two strong tools

"The drug suppresses the immune system a bit. If you suppress it more with a higher dose, you get a better effect, but you also might get more side effects," he says.

He further notes that the side effects include an increase in infection and injection site reactions. There is theoretical concern about the development of lymphoma and demyelinating diseases such as multiple sclerosis.

Cyclosporine and other immunosuppressive agents are clearly associated with an increase in lymphomas and squamous cell carcinomas of the skin. That same clear-cut increase has not been evident, so far, with the TNF-alpha blockers; however, there may be a slight increase in lymphomas, Dr. Lebwohl says.

"In the review that I did, we did not find an increase in squamous cell carcinoma, although there have been a few case reports of squamous cell carcinomas in patients who had started on TNF-alpha blockers," he says.

"There has been a slight increase in lymphomas in patients treated with these drugs - though it is not statistically significant. There has been at least one patient treated with etanercept and another treated with infliximab who developed lymphomas while they were getting these drugs and, when the drugs were stopped, the lymphomas disappeared. So, you know that there is some role that immunosuppression plays in the development of lymphomas, and, therefore, there is a concern when we give these drugs to patients that there might be a small increase in lymphoma risk."

More good news

Another promising tool in the fight against psoriasis is the not-yet-approved anti-IL-12, which might be anti-IL-23, according to Dr. Lebwohl.

Remicade maker Centocor has presented data on anti-IL-12, showing that even one injection helps patients, and about 80 percent of patients who got four injections achieved substantial improvement. The drug is just starting phase 3 clinical trials.

"So far, there are no known side effects," Dr. Lebwohl says. "Presumably, IL-12 has a role in the immune system and just blocking that one piece of the immune system makes psoriasis better."

No magic bullet - yet

While these psoriasis treatment options are exciting, Dr. Lebwohl admits that dermatologists do not yet have a drug option for psoriasis that is hands-down superior to cyclosporine. The approval of the biologics for psoriatic arthritis represents the first substantial step toward achieving the goal of equal or greater efficacy to cyclosporine but with fewer, less dangerous side effects.

"Cyclosporine knocks out a whole portion of the immune system. These just knock out one part of it. So, they should be less immunosuppressive and also do not have the kidney toxicity that we experience with cyclosporine," Dr. Lebwohl says. "For those reasons, we would hope that they would be safer, and it would appear that they are."