Recently approved and investigational biologic therapies are changing the way dermatologists treat psoriasis, a chronic disease that physically and emotionally challenges 4.5 million Americans. As more research is conducted into the effectiveness of these biologics, they are showing great promise for improving the health and well-being of patients with psoriasis.
Speaking today at the 63rd Annual Meeting of the American Academy of Dermatology (Academy), dermatologist Jeffrey M. Weinberg, M.D., assistant clinical professor in the department of dermatology at Columbia University, New York, N.Y., discussed the aims of biologics for the treatment of psoriasis and psoriatic arthritis.
“Biologics are designed to provide select, immunologically directed intervention within the body to target psoriasis-causing reactions, controlling the condition and helping to prevent flare-ups,” said Dr. Weinberg. “Biologics also are proving to have fewer side effects than traditional psoriasis therapies, meaning patients can find relief for longer periods of time without having to switch treatments.”
Caused by the unusually rapid growth of skin cells due to faulty signals from the body’s immune system, psoriasis is characterized by thick, red, white or scaly patches on the skin’s surface. The extra cells build up on the skin’s surface and form plaques – usually around the knees, elbows, scalp, hands, feet or lower back – causing itching and severe discomfort.
Research has shown that the activation of T-cells, a type of white blood cell, is the key immune system trigger in the development of psoriasis. Once activated, these cells release cytokines – chemicals used by the immune system to communicate messages. In psoriasis patients, these cytokines signal skin cells to reproduce and mature at an accelerated rate, thereby setting off other reactions that lead to psoriatic lesions forming on the skin.
Two biologics — alefacept and efalizumab — are approved by the U.S. Food and Drug Administration (FDA) for treating psoriasis and a third biologic – etanercept – is FDA-approved for the treatment of both psoriasis and psoriatic arthritis. These three biologics are approved for treating adults with moderate to severe psoriasis.
Alefacept is a biologic that is given by intramuscular injection at a dermatologist’s office once a week for 12 weeks and works by directly reducing the number of activated T-cells in the skin, thereby stopping the cycle of psoriasis.
In a recent study, patients underwent two alefacept treatment courses, each with a 12-week treatment and 12-week follow-up phase, that did not include biologic treatment, only monitoring. During the first course of treatment, patients’ Psoriasis Activity and Severity Index (PASI) scores were recorded. The PASI is the standard measurement tool to determine what percentage of the body is affected by psoriasis and how severe a patient’s psoriasis is at any given time. Nearly 14 percent of patients achieved a 75 percent reduction from their baseline PASI around week 14. After the 12-week follow-up phase, patients from this same trial were randomly selected to receive a second course of alefacept and they showed additional improvement, with 40 percent achieving between 50 and 75 percent PASI improvement almost immediately upon beginning the second course of treatment.
“Alefacept provides a long period of remission for patients, in many cases from seven months to one year,” stated Dr. Weinberg. “Once remission lapses, a repeat 12-week course of therapy can be administered if 12 weeks have passed since the last shot was given, making alefacept a viable long-term treatment option.”
The biologic efalizumab prevents the migration of activated T-cells into the skin from the lymph nodes. Injected into the skin by patients at home, efalizumab is taken on a weekly basis.
Clinical trials of various strengths of efalizumab as compared to placebo showed nearly 30 percent of patients achieved a 75 percent or more improvement from their baseline PASI as compared to only 3.4 percent of patients treated with the placebo who achieved that same PASI score. “What is proving most effective about efalizumab is that it works rapidly to treat psoriasis, allowing almost immediate relief in most cases,” stated Dr. Weinberg. “However, once efalizumab is stopped, signs and symptoms of psoriasis usually reappear.”
Etanercept is a biologic approved for the treatment of both psoriasis and psoriatic arthritis, a condition that can affect joints in the hands, feet, knees, hips, shoulders, lower back and ankles, making them painfully swollen, red and stiff. Etanercept is injected by the patient once or twice a week at home and can provide long-term therapy.
“Because etanercept works by neutralizing a cytokine that is primary to immune response, when taken continually it can greatly benefit patients who experience severe psoriasis flare-ups,” said Dr. Weinberg. “It also is advantageous because it treats not only psoriasis but psoriatic arthritis, which affects more than 25 percent of patients with psoriasis.”
In clinical trials evaluating etanercept, the biologic was injected in 25 mg and 50 mg doses twice weekly by patients. After 12 weeks at the 25 mg dose, nearly 34 percent of patients achieved a 75 percent or more improvement from their baseline PASI. At the higher dose, 49 percent of patients achieved a 75 percent or more PASI improvement at 12 weeks, and at 24 weeks, nearly 59 percent of patients achieved that PASI improvement.
Another biologic currently in phase III testing with the FDA is infliximab. This biologic blocks TNF-?, (tumor necrosis factor-alpha), one of the main cytokines that signals the psoriasis cycle to begin. Infliximab can be given intravenously in the dermatologist’s office over a course of several weeks to reduce the severity of psoriasis.
“Biologics are a positive step forward in finding innovative ways to treat psoriasis,” stated Dr. Weinberg. “As more and more research is being conducted in this area, I’m confident that dermatologists can help more patients with psoriasis find the best therapy available for their condition.”