Medical Advances in Psoriasis

Homing in on more effective treatments—and perhaps even a cure -- for this skin-ravaging disease

Psoriasis isn’t simply dry skin. It’s an autoimmune disease characterized by inflammation of the skin (and in the joints of people with psoriatic arthritis) and accelerated turnover of skin cells, which causes excessive flakiness, itchiness and sensitivity. The National Institutes of Health lists more than 500 ongoing or recently completed studies looking for better ways to treat psoriasis—or, ideally, to cure it. “The biggest breakthrough in psoriasis research in recent years has been our increased understanding of the mechanisms that govern this disease,” says Bruce Bebo, Ph.D., director of research and medical programs at the National Psoriasis Foundation. “That understanding is leading to exciting, more effective treatments.”

Killing the messenger. In the summer of 2000, researchers at the University of Washington in Seattle successfully treated psoriasis with etanercept (Enbrel), a drug that has been approved and is now being used for the treatment of rheumatoid arthritis. Etanercept is a biologic drug that inactivates tumor necrosis factor (TNF), an immune system protein that carries messages to other cells in the body. Its effectiveness in treating psoriasis provided the first evidence that TNF plays a role in psoriasis by telling other cells to increase inflammation and speed up skin cell turnover. Etanercept appears to work by intercepting those messages. Research since has resulted in the development and FDA approval of four other TNF-blockers in addition to etanercept: adaliumumab (Humira), infliximab (Remicade) and golimumab (Simponi), as well as certolizumab (Cimzia), which has been approved for Crohn’s disease and rheumatoid arthritis.

Getting more specific. Further research into the roles that immune system messenger cells play in psoriasis is allowing scientists to develop drugs that can inactivate the immune system cells responsible for psoriasis flares while safeguarding the immune system cells that protect the body from viruses, bacteria, cancers and other invaders. This way, a person’s psoriasis can be treated without compromising the immune system and leaving that person vulnerable to other diseases. The first such drug, ustekinumab (Stelara), was approved last year. It is a monoclonal antibody (a protein designed by using molecular genetics techniques) that neutralizes immune system messenger cells—namely, interleukin 12 (IL12) and interleukin 23 (IL23). “Clinical trials of this drug showed even more robust effects in treating psoriasis than the TNF-blockers,” says Dr. Bebo. At least four other interleukin-blocking drugs are in research trials and may be available soon.

Popping a pill. The biologic drugs used to treat psoriasis are all given by injection or intravenously, but there are new oral medications in the works. The most innovative of these target the action of kinases—enzymes inside immune system cells that are key to inducing inflammation of the skin. Currently, there are at least four kinase inhibitors in advanced trials.

Rubbing it in. Because topical medication typically carry the lowest risks of side effects, they tend to be the first-line treatments for mild to moderate psoriasis, or psoriasis that covers a limited area of the body. In general, though, they haven’t been as effective for severe psoriasis as biologic medications. That may soon change. Five years ago the FDA approved Taclonex, an ointment that combines the anti-inflammatory powers of vitamin D with topical betamethasone, a steroid. New vitamin D/steroid preparations are in the research pipeline. Also in the works: some topical versions of cytokine inhibitors, designed to block the immune reactions that cause psoriasis, much like injectable biologic drugs. (Cytokines are molecules produced by the immune system that help to coordinate immune responses.)

A future cure? Psoriasis is primarily a genetic disease. Scientists believe that at least 10 percent of people inherit one or more of the genes that predispose them to psoriasis; however, only 2 to 3 percent actually develop the condition. Doctors may soon be able to identify all of the genes involved in psoriasis, thanks to a biobank created by the National Psoriasis Foundation (NPF), which has collected DNA samples from more than 1,700 psoriasis patients. Those samples are now being examined by researchers at the University of Michigan Health System in hopes that they’ll help scientists not only to identify genes that increase a person’s risk factor for developing psoriasis, but also to better understand the connection between psoriasis and other autoimmune conditions, such as Crohn’s disease.

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