Biologics revitalize medical dermatology

"This is a very exciting time, particularly in medical dermatology," says Ivor Caro, M.D., medical director of dermatology, Genentech.

"For many years," he says, "people thought psoriasis was related to epidermal hyperproliferation. But only recently has it been recognized as an autoimmune, T-cell mediated skin disease. This is really where the new biologics in dermatology have entered the picture. They're aimed at treating the immune mechanism in psoriasis. The way I look at it, psoriasis is an entry point. Dermatologists are accepting the new biologic agents. They are much more savvy and educated about immunology in general, and with reference to the immunopathogenesis of skin diseases, there will be more investigations and studies utilizing the different biologic agents in other diseases ranging from atopic dermatitis to the primary blistering diseases, such as pemphigus and pemphigoid, and the other classic autoimmune skin diseases such as lupus, dermatomyositis and vasculitis."

The newer T-cell and B-cell agents, as well as cytokine inhibitors, might all have applicability in various autoimmune diseases, some of which may have dermatologic manifestations.

"B-cells are important in many autoimmune diseases. Antibodies are present. For example, we certainly have elevated rheumatoid factor in rheumatoid arthritis (RA). And although it has not classically been thought of as being a B-cell disease, there is increasing evidence that agents that work against B-cells have efficacy in RA," Dr. Caro explains.

At the same time, ongoing studies are examining the role of B-cell agents in systemic lupus erythematosus.

"And there's great interest in looking at the T-cell agents in other potentially T-cell mediated dermatological and systemic diseases," Dr. Caro says. "What I find fascinating is that we're really talking about targeted therapies. Both the monoclonal antibodies and the cytokine inhibitors are very specifically targeted therapies, and the advantage many of us see is the potential that these may have improved safety profiles because they're less broad-spectrum in their immunomodulating properties."

Along these lines, Genentech is in the early stages of investigating a topical hedgehog antagonist in BCC that, while not strictly speaking a biologic drug, takes a similarly focused approach.

"The specialty is becoming much better about looking at and designing therapies that are much more specific to disease entities," he says.

At the same time, dermatologists' experience and expertise with existing biologic drugs continues to grow.

"There are now three biologics approved to treat psoriasis in the United States," Dr. Caro says. "And more and more dermatologists are becoming comfortable in using one, two or all three of these new biologics."

Amevive (alefacept, Biogen) represents the first biologic to be approved for psoriasis. Its primary mode of action is to deplete memory-effector T-cells. Another T-cell agent, Raptiva (efalizumab, Genentech), won U.S. Food and Drug Administration approval for psoriasis in late 2003 and, more recently, was approved in Europe and Australia. Enbrel (etanercept, Amgen/Wyeth), a TNF-alpha blocker, completes the list.