THURSDAY, June 7, 2001 (HealthDayNews) -- A monoclonal antibody produced by genetic engineering has given excellent results in its first trial against psoriasis, the disfiguring and painful skin disease, researchers report.
Larger-scale trials of the antibody, called infliximab, are scheduled to begin late this year or in early 2002, says Thomas Schaible, executive director for medical affairs of Centocor, a bioengineering company that markets the product under the brand name Remicade.
The hope is that infliximab will be provide a psoriasis treatment that is both safe and effective, says Dr. Alice B. Gottlieb, professor of medicine and director of the clinical research center at UMDNJ-Robert Wood Johnson Medical School in New Brunswick, N.J., who initiated the trial.
"All the Food and Drug Administration-approved options do not work well or are toxic," Gottlieb says. Among the currently approved treatment for psoriasis, which affects about 2 percent of Americans, cyclosporin, the most effective, can cause high blood pressure and kidney problems, methotrexate is toxic to the skin and bones, and ultraviolet radiation with the drug psoralen has been associated with skin cancer, she says.
A major goal of the trial, Gottlieb says, was to test the theory that the overgrowth of skin cells and inflammation of psoriasis is due in large part to the activity of tumor necrosis factor-alpha (TNF-alpha), an immune system molecule that increases reproduction of skin cells and inflammatory cells. Monoclonal antibodies seek out a specific target, and in this case infliximab blocks the activity of TNF-alpha. It currently is approved for treatment of rheumatoid arthritis and Crohn's disease, a bowel disorder.
"A lot of things are elevated in psoriatic lesions," she says. "The question is: Which is more important than the others? The point of the study was not only to see whether infliximab is safe and efficacious in moderate-to-severe psoriasis but also to see if you can clear psoriatic plaques with targeted immunotherapy."
The trial enrolled 33 patients. Eleven were given a placebo, an inactive substance, 11 got three intravenous injections of infliximab at a dose of 5 milligrams per kilogram of body weight, and the other 11 got double that dose.
After 10 weeks, nine of the 11 patients in the 5-mg group had good-to-excellent responses, as did 10 of the 11 in the 10-mg group, says a report in the June 9 issue of The Lancet. Only two of 11 patients in the placebo group had similar responses. No serious side effects were reported.
Infliximab is one of a group of promising treatments for psoriasis in various stages of testing, says Dr. Mark G. Lebwohl, chairman of the department of dermatology at the Mount Sinai School of Medicine in New York City. They include another TNF-alpha monoclonal antibody, etanercept, and agents that act against a variety of molecular processes in psoriasis.
Infliximab "looks very promising," Lebwohl says. "It looks like there were long remissions, and a high proportion of patients had dramatic responses. There is clearly something beneficial going on here."
But more studies are needed to see whether the drug produces long-lasting responses, and if there are serious long-term side effects, they will have to be "examined and addressed," Lebwohl says.
Details of the larger trials are being worked out with the Food and Drug Administration, Schaible says, "but it would be safe to say that there will be a large, multi-center, probably international, type of study."
What To Do
While infliximab can legally be prescribed for psoriasis, Gottlieb advises against it. "This is the first time the drug is being used as monotherapy [single-drug therapy]," she says. "We don't have safety data on a large number of patients with monotherapy, so it is better to be treated as part of a study where patients are being monitored carefully." Psoriasis patients should try to join a clinical trial, she advises.
General information about psoriasis is available from the National Institute of Arthritis, Musculoskeletal and Skin Diseases. For information about clinical trials, go to the National Psoriasis Foundation.
Sample other HealthDay articles about psoriasis.
