Physician predicts better psoriasis treatments

Salt Lake City - Biologic drugs have changed the lives of many psoriatic patients with severe disease, but the potential benefits offered by biotechnology are only beginning to be realized.

Where we are now Biotechnology has brought significant credibility to our understanding of the pathogenesis of psoriasis, according to psoriasis researcher Gerald G. Krueger, M.D., professor of dermatology at the University of Utah School of Medicine here.

"Before biologic agents became available, we were quite certain that psoriasis was an autoimmune, T-cell mediated disease," Dr. Krueger tells Dermatology Times. "Everything that has come from the response of this disease to the biologic response modifiers has been in complete harmony with that understanding."

"Most of us have felt for some time that psoriasis is a complex, multigenic disorder, and because of that, we would anticipate there are treatments that should work well in one person but not another. Indeed, that seems to be the case."

So far, biotechnology has given us etanercept for psoriatic arthritis and recently psoriasis, alefacept for psoriasis and efalizumab for psoriasis, according to Dr. Krueger.

"Unlike conventional treatments, these biologic agents can be used in a fashion that allows continuous control," he says. "Our non-biologic agents frequently have acute or chronic side effect profiles that limit their use. We use them until the disease is better, then switch to a lower dose, switch to another treatment or stop the treatment, and so on. We really haven't appreciated the concept of continuous control as a viable option.

"We don't have many years of experience with the biologics yet, but if the current adverse event profile for the biologics holds, we won't have to keep rotating new treatments as we felt we need to do with conventional treatments."

On the horizon Each with their pros and cons, infliximab and adalimumab are expected to be approved for psoriasis in the near future, according to Dr. Krueger.

"Infliximab, though very effective, is challenging to use for two reasons," he says. "First, the physician must warn the patient of potential adverse effects which include early onset congestive heart failure, lymphoma, death due to sepsis, and vasculitis. Second, infliximab must be given by IV infusion over two to four hours. For these reasons I envision no dermatologist using infliximab as routine. Yet for severe psoriasis, infliximab has worked when no other drug has worked. A few dermatologists are setting up facilities just to give infliximab."

Infliximab is 13 percent murine, Dr. Krueger says.

"The likelihood of people making antibodies to the murine element is high unless the patient (1) takes an immunosuppressive agent such as methotrexate or (2) takes infliximab on a regular basis." (Infliximab, when taken regularly - e.g., every eight weeks - has been hypothesized to act as its own suppressant.)

Adalimumab Unlike infliximab, adalimumab is a completely human antibody, according to Dr. Krueger.

"Adalimumab is next in line for psoriasis, then psoriatic arthritis," he predicts. "In my opinion, for psoriasis, 40 mg of adalimumab taken every-other-week is as effective as 50 mg of etanercept taken twice a week."

Other promising agents for psoriasis include anti-interleukin-12, a drug in early phase 2 trials that clearly works in psoriasis.

"One injection and the psoriasis is gone," Dr. Krueger says.

Additional treatments include, onercept, a TNF receptor decoy in phase 3 trials in Europe; anti-CTLA (cytotoxic T-lymphocyte-associated molecule)-4, which interferes with activation of T cells; and an antibody (under development for use in multiple sclerosis) that blocks the binding of VLA (very late antigen)-4 with its receptor, Dr. Krueger says.

"I would be surprised if blocking VLA-4 would also not work in psoriasis," he adds.