Cyclosporine for psoriasis

People whose psoriasis cannot be controlled by topical medications applied directly to affected areas of the skin may turn to systemic, or internally administered, drugs, to ultraviolet light treatments, to biologic therapies, or to some combination of them. In the United States, the three most common systemic medications for psoriasis are cyclosporine, methotrexate, and acitretin (Soriatane). This page discusses cyclosporine.

Cyclosporine (Neoral and others)

What is it?
Cyclosporine is an immunosuppressant medication that has been widely used since the early 1980’s to prevent rejection of organ transplants. In 1997, one particular formulation of cyclosporine, Neoral, gained FDA approval for the treatment of severe psoriasis.

How is it administered?
Psoriasis patients usually take cyclosporine in pill form, twice a day. Because long-term use of cyclosporine damages the kidneys (see below, Drawbacks), patients normally receive multiple short courses of cyclosporine therapy, each lasting about 12 weeks, with “rest” periods in between.

How well does it work?
Cyclosporine is highly effective at controlling psoriasis. Overall, about 70% of patients in clinical trials experienced at least a 75% improvement in their psoriasis symptoms as measured by the Psoriasis Area and Severity Index (PASI). The PASI takes into account both the fraction of the body surface area covered by psoriasis plaques and the severity of the plaques (e.g. the degree of redness and scaling). “PASI 75,” as this level of improvement is known, is the standard typically used by the U.S. Food and Drug Administration (FDA) in evaluating the effectiveness of potential psoriasis treatments.

Advantages
Although Cyclosporine cannot be used long-term, it can be very helpful as an initial therapy to bring severe psoriasis under control or to treat periodic flares. Patients can combine intermittent short-term courses of cyclosporine with long-term use of a less toxic medication. Although cyclosporine is considered less harmful to a developing fetus/child than methotrexate or acitretin, this advantage may no longer be as important since the advent of the biologics, which may be a better choice for women who are or may become pregnant. But this is a complex question that should be discussed with a physician in advance of a pregnancy.

Drawbacks
The most serious problem with cyclosporine is that long-term use almost inevitably leads to kidney damage, although the damage is often reversible if patients stop taking the medication. Therefore, psoriasis patients should not use cyclosporine continuously for more than 1-2 years. The preferred treatment strategy is give multiple short courses of cyclosporine therapy with breaks in between to allow the kidneys to recover from the drug’s toxic effects. Patients receiving cyclosporine need to undergo regular blood tests to monitor their kidney function. Those with pre-existing kidney disease are generally advised not to use cyclosporine.

Psoriasis patients taking cyclosporine also often develop high blood pressure. Usually, the increase in blood pressure is mild to moderate, does not require treatment, and resolves when the course of cyclosporine therapy ends.

Due to its immunosuppressant effects, cyclosporine can increase the risk of infection and cancer. So far, these problems have only been clearly demonstrated in transplant patients who take higher doses of cyclosporine for longer periods of time than psoriasis patients. Still, because of the potential risk, cyclosporine is not generally considered safe for psoriasis patients who have a history of cancer or for those whose immune system is impaired, for example by HIV infection.

How does it work?
Cyclosporine inhibits the production of a chemical called interleukin-2 (Il-2) inside certain immune cells, particularly T lymphocytes. T lymphocytes need Il-2 to become fully active and without it, their ability to mount an immune response is severely impaired. Psoriasis may be caused by hyperactive, mis-regulated T lymphocytes, so the dampening effect of cyclosporine on T lymphocytes could explain why the drug is effective against psoriasis.