Advances in psoriatic therapy

May 1, 2007

Biologics have brought much relief and promise to patients who have moderate-to-severe psoriasis. Yet, there are a number of rare adverse events that may occur. Here is an up-to-date review of these psoriasis treatments.

Key Points

Washington - Dermatologists continue to deliberate over how to best treat patients with moderate-to-severe psoriasis. One expert offered a review of biologics, as well as other psoriasis therapies on the horizon, at the 65th Annual Meeting of the American Academy of Dermatology (AAD), here.

"There are four basic strategies for targeted biologic immunotherapy. These are: 1) to reduce or eliminate pathogenic cells, like alefacept (Amevive, Biogen Idec), 2) to prevent pathogenic cell activation, like efalizumab (Raptiva, Genentech), 3) to alter cell differentiation, in this case, immune differentiation, and 4) to block effector function by binding postsecretory cytokines, such as the tumor necrosis factor (TNF) inhibitors. Currently, we have drugs on the market that can do strategies 1, 2, and 4," says Jeffrey M. Weinberg, M.D., of the department of dermatology, St. Luke´s-Roosevelt Hospital Center and Beth Israel Medical Center in New York.

INFLIXIMAB

According to Dr. Weinberg, recent studies show that PASI-75 (the Psoriasis Area and Severity Index) improvement with infliximab at 10 weeks is approximately 80 percent. He says this IV-administered TNF–alpha inhibitor boasts an excellent response in speed of onset, durability and efficacy.

"Safety concerns of infliximab include increased risk of infections, development of auto-antibodies/lupus, malignancies/lymphomas, hepatotoxicity, pneumonia and congestive heart failure. Serious infections, including sepsis, have been reported. Caution should be used in treating patients with chronic infections or a history of recurrent infections. Also, a PPD test is required in patients taking infliximab," Dr. Weinberg says.

He says to exercise caution in those patients taking more than 5 mg/kg of infliximab, as mild congestive heart failure may worsen. Also, there is increased risk of developing demyelinating disorders, such as multiple sclerosis, optic neuritis and seizures.

ETANERCEPT

Etanercept (Enbrel, Amgen/Wyeth) is a TNF–alpha inhibitor that is FDA-approved for rheumatoid, juvenile rheumatoid and psoriatic arthritis; ankylosing spondylitis; and psoriasis. The starting dose in psoriasis is 50 mg twice weekly for three months, followed by a maintenance dose of 50 mg qwk.

"Starting doses of 25 or 50 mg per week of etanercept also work very well. In recent studies at these doses, the median time to PASI 50 was one month and to PASI 75 was two months," Dr. Weinberg says.

Dr. Weinberg cited a study presented at the AAD in 2006 that showed that etanercept was found to be safe and effective at a dosing of 50 mg, twice weekly for 96 weeks.

Dr. Weinberg says patients with active infections, including chronic or localized infections, should not use etanercept, and caution should be exercised for patients with a history of recurring infections or underlying conditions that predispose to infection, such as diabetes. As with infliximab, there are safety concerns regarding demyelinating disorders and congestive heart failure, as well as a possible increased incidence of malignancies.

ADALIMUMAB

Adalimumab (Humira, Abbott) is a human IgG1 monoclonal TNF–alpha antibody that works by binding to TNF–alpha and inactivating it, which results in a reduction of inflammatory activity. It is FDA-approved for rheumatoid arthritis and psoriatic arthritis.

At the AAD, a poster presented phase 3 data from the plaque psoriasis 1,100-patient study. Data showed that the side effects of adalimumab are similar to those seen in other TNF inhibitor drugs.

Dr. Weinberg cited a study in which there was a statistically significant superior efficacy of adalimumab compared with methotrexate in patients with moderate-to-severe psoriasis.

"Response to adalimumab was rapid and was well-tolerated by patients, with a mean percentage PASI improvement of 57 percent achieved at week four of the study," Dr. Weinberg says.