Psoriasis: Latest Treatment Trends


(7/26/05)- The Merck Manual, 16th Edition, defines psoriasis, under the generic heading of SCALING POPULAR DISEASES, as "A common, chronic, recurrent disease characterized by dry, well-circumscribed, silvery, scaling papules and plaques of various sizes." To those who suffer from this disease it is a painful, disfiguring dermatological condition with visible unsightly symptoms that create social stigma.

Estimation is that 14 million people suffer this condition worldwide. More than 5 million Americans have psoriasis, and they spend between $1.6 billion and $3.2 billion each year to treat the disease, according to the National Psoriasis Foundation (NPF). Between 150,000 and 260,000 new cases are diagnosed each year, including 20,000 in children younger than 10. There are expectations in the drug industry that sales of antipsoriatics will pass the 2 billion-dollar mark in 2007.

According to The Merck Manual, "About 2% to 4% of the white population, and far fewer blacks, are affected. Onset is usually between ages 10 and 40, but no age is exempt…Except for the psychological stigma of an unsightly skin disease, general health is unaffected unless arthritis, intractable exfoliation, or severe, widespread postulation develops." It is caused by the non-proliferation of keratinocytes (skin cells that make keratin, the substance that comprise hair, nails and skin).

Psoriasis was recognized as an autoimmune disease after the discovery of T-cell involvement, but the factors that trigger the disorder are varied and unpredictable.

A Dec. 12 news release from The University of Texas M.D. Anderson Cancer Center in Houston says scientists have identified a protein called STAT3 that initiates psoriasis when the body's immune system is activated to fight off a wound, burn, or some other invasion. According to Lynne Kincaid, writing in Drug Discovery Today (Vol. 10, No. 13, July 2005), "At least a dozen separate chromosomal loci have been implicated, but the strongest causative factors are thought to be environmental."


A search of the professional literature suggests that psoriasis is currently incurable. There exist many treatments to calm the inflamed areas. The problem is that the skin becomes resistant to the treatment or side effects occur, including immunosuppression, photosensitivity, increased risks of skin cancer and renal or hepatic toxicity. One survey of 23,622 psoriasis patients, done in 2002, indicated that 11.3% of the patients refused treatment because of the side effects. An ongoing phase III trial conducted by Isotechnika of a calcineurin inhibitor (ISA247) raised the number of patients in their study because of the demand. The following information was found on Isotechnika’s web site: "Our lead candidate, ISA247, is an immunosuppressive compound currently being investigated for the treatment of psoriasis and for the prevention of organ rejection in renal transplant patients. In less than seven years, ISA247 has successfully progressed through discovery, pre-clinical, and Phase II human clinical trials. All studies to date suggest that ISA247 is more potent and less toxic than currently available treatments within our drug class".

Presently, there are less than 160 compounds in development as compared to 2000 for cancer. The phase III trial of onercept (Serono, a "global biotech concern") was recently discontinued due to two patients developing sepsis.

The standard treatment for moderate to severe psoriasis consists of topical agents having a low incidence of adverse effects. Many of them soothe and thus provide a form of relief from the symptoms of itching and burning. Systemics are prescription medications that affect the entire body, and are usually reserved for patients with moderate to severe psoriasis. Biologics are a type of systemic medication. Biologic medications are developed from living sources, such as cells, rather than combinations of chemicals like traditional drugs. Generally, they are designed to block or eliminate various immune system cells involved in psoriasis and psoriatic arthritis. Etanercept (Enbrel) and alefacept (Amevive) are the first biologics that have shown some clinical success. Etanercept, originally approved for severe psoriasis has been now approved for moderate-to-severe psoriasis. Other systemic medications for these diseases can also impact the immune system, but usually in a broader, less specific way.

Cyclosporine is a prescription systemic medication used to treat psoriasis. Cyclosporine has been available since 1995 to help prevent organ rejection in transplant patients. In 1997, the FDA approved Neoral (one brand name of cyclosporine) as a psoriasis treatment.

Methotrexate is a systemic medication usually sold as a generic. Initially used to treat cancer, methotrexate was discovered to be effective in clearing psoriasis in the 1950s and was eventually approved for this use by the FDA in the 1970s. (Note: this drug carried a black box warning in the PDR Monthly Prescribing Guide we consulted for this article.)

Soriatane (also known by its generic name acitretin) is a prescription medication called an oral retinoid, which is a synthetic form of vitamin A. Synthetic retinoids were introduced as experimental drugs in the mid-1970s and were approved in the United States in the 1980s. Soriatane is currently the only oral retinoid approved by the FDA specifically for treating psoriasis. Other systemics are Accutane, Hydrea, mycophenolate mofetil, sulfasalazine, 6-Thioguanine.

Sufferers of psoriasis are also turning to alternative or complementary therapies. If you would go to the Psoriasis Foundation site, you would be given the following information: "Sunlight and water are natural therapies that can help improve psoriasis and/or psoriatic arthritis for many people. Eighty percent of the people who use regular daily doses of sunlight enjoy improvement or clearing of their plaque psoriasis. Water can help soften psoriasis lesions. Climatotherapy is a term used to describe the combination of natural sunlight and water, such as the ocean or other bodies of water, to treat psoriasis. In particular, climatotherapy refers to certain locations around the world, like the Dead Sea in Israel, where the environment and natural elements are said to be especially therapeutic for psoriasis and/or psoriatic arthritis." They conclude with "No matter what it is called or where it takes place–in the backyard, at the beach or in the bathtub–sun and water may make a difference in how psoriasis and psoriatic arthritis."

Future Treatments:

The new treatments being explored involve trying to target the disease process before symptoms appear. They target the inflammation process itself. This involves tumor necrosis factor (TNF) inhibitors in particular TNF-a. According to an article in Drug Discovery Today (July 2005; 10(13):884-886), “TNF-a is important in the pathogenesis of psoriasis because it induces synthesis of interleukin-1 (IL-1) and IL-8, which cause the inflammation. TNF-a also promotes keratinocyte proliferation (the building block of the skin) and angiogenesis (the growth of new blood vessels) and thus inhibiting this cytokine should halt the development of the disease at multiple loci.” This class of potential drugs is mildly immunosuppressive and the risk of sepsis as seen with onercept is always present. Secondly, this category of drugs must be carefully stored and must be administered parenterally (Taken into the body or administered in a manner other than through the digestive tract, as by intravenous or intramuscular injection). Enbrel and adalimumab (Humira) are available for psoriasis. Abbott has a drug in phase III trials for psoriasis. The same is true for Centocor’s autoimmune treatment infliximab (Remicade). Biotech launched a topical anti IL-8 antibody product (ABC cream) in China. Some experts consider these IL antagonists as not crucial in the development of psoriasis, so this research may in the long run prove highly efficacious.

Drug Discovery Today (ibid.) article suggests "Additional strategies include selectin antagonists designed to stop immune cells reaching the inflamed skin and causing further damage, various conserved domain antigen receptor antagonists to halt T-cell activation and traditional drugs such as retinoids, optimized with new formulation technologies… The outlook for psoriasis sufferers is improving with a range of new treatments maturing into safer and all around better products…Alternatively, if costs continue to rise, it is not unimaginable that policy makers and insurers will decide not to pay for drugs to treat a non life-threatening condition-a feasible consequence that could leave sufferers itching mad!"



Harold Rubin, MS, ABD, CRC, Guest Lecturer
July 26, 2005

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