Immunosuppressants and Biologics

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The first products to be developed in this field came from other areas of medicine.

Methotrexate was discovered to be effective in clearing psoriasis in the 1950s and was eventually approved for this use in the 1970s. In psoriasis, methotrexate works by preventing the excessive division and multiplication of skin cells that causes the skin scaling and raised plaques in this condition. It is used when the condition is severe and unresponsive to conventional treatments as it has many potential side effects.

Ciclosporin is another immunosuppressant, originally used to prevent transplant patients from rejecting their new organs. Doctors noticed that transplant patients who had a previous history of psoriasis tended to have fewer plaques post transplant and research suggested that it was the ciclosporin that was having this effect.

Ciclosporin is highly effective in severe psoriasis refractory to other treatments. Its exact mechanism of action is not fully understood, but it may inhibit epidermal hyperproliferation by suppressing T lymphocyte activity in the dermis and epidermis of psoriatic skin.

The "Biologics" are relatively new entrants into the field of psoriasis management and are made from biological (human or animal based) proteins rather than artificial chemicals, much in the way that insulin was made from animal sources in the past.

Biologics are different from other medications for psoriasis and psoriatic arthritis as they are designed to block both diseases in the immune system rather than waiting to treat the symptoms of the disease.

It is thought that overactive cells in the immune system set off a series of events in the body, eventually causing psoriasis to develop on the skin and arthritis symptoms to develop in the joints. Biologics work by blocking the action of specific immune cells that cause these cells to misbehave by either reducing the number of these cells in the skin and blood or by blocking the activation of the immune cells or the release of chemicals from them.

Biologics target overactive cells in the body. Some target a type of immune cell called T cells while others target the chemical messengers released by activated T cells.

In psoriasis certain T cells are mistakenly activated and move into the skin. Once in the skin they begin to act as if they are fighting an infection or healing a wound and this results in a rapid growth of skin cells. In psoriasis skin cells grow much faster than normal and this over production causes cells to pile up at the skins surface. Some biologics act by preventing the activation and/or migration of T cells, by reducing the number of psoriasis involved T cells in the body, or both.

TNF-alpha (tumour necrosis factor alpha) is produced in excess amounts by activated T cells. The messages communicated by TNF alpha lead to the rapid growth of skin cells found in psoriasis or to the joint pain and stiffness associated with psoriatic arthritis.

A number of biologic medications have been introduced to treat rheumatoid arthritis and other diseases by binding to TNF alpha and preventing it from communicating with cells. It has been found that these TNF alpha agents are also effective to different degrees in treating psoriasis and psoriatic arthritis.

The biologic medications are very expensive and so they have been the subject of a lot of investigations with doctors being advised when they should be administered. They cost between £8 - £10,000 per patient per year, only work in a proportion of patients and their long term safety has not yet been established. As a result they are not considered first line therapy.

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