Cyclosporine

Cyclosporine, also called cyclosporine A, is a medication that suppresses the immune system. It is commonly used to prevent rejection in patients who underwent liver, kidney, or heart transplants, and to treat the symptoms of rheumatoid arthritis.

Cyclosporine is also used treat symptoms of psoriasis and inflammatory eye conditions, and has been reported to be effective in treating those of ocular sarcoidosis. It is often used as a steroid-sparing agent in patients who do not tolerate or respond to corticosteroids, such as prednisone.

Cyclosporine is available in two forms, modified and non-modified. The non-modified version is marketed under the brand name Sandimmune, and the modified version under the brand names Neoral and Gengraf. Modified cyclosporine has a higher bioavailability, or absorption rate, than non-modified cyclosporine and is used at a different dose. The two forms cannot be used interchangeably.

How cyclosporine works

As an agent that suppresses the immune system, cyclosporine acts on immune cells called T-cells, the main cell type that form the granulomas, or clumps of immune cells, that are the hallmark of sarcoidosis.

Cyclosporine forms a complex with a protein called cyclophilin and inhibits the activity of calcineurin. Calcineurin is a crucial factor for the production of a cell signaling molecule called interleukin-2 (IL-2), which is essential for the function and survival of T-cells.

Cyclosporine in clinical trials

Cyclosporine’s effectiveness in treating symptoms of ocular sarcoidosis has not been evaluated in a clinical trial. But two case reports suggest that patients with this condition might benefit from cyclosporine treatment.

The first report describes the case of a 36-year-old man whose conjunctiva, the membrane that covers the inner surface of the eyelids, contained sarcoid granulomas. Treatments given him, including prednisone — a corticosteroid that is standard therapy for ocular sarcoidosis — over the course of six months led to only mild improvement. Treatment with eye drops containing 0.05 percent cyclosporine four times a day led to complete resolution of the granulomas within four weeks.

In the second report, a 58-year-old woman with conjunctival sarcoidosis was also given eye drops containing 0.5 percent cyclosporine four times a day. The granulomas resolved entirely within two weeks, the researchers noted.

A randomized controlled trial tested the effectiveness of cyclosporine in patients with pulmonary sarcoidosis. The trial included 37 patients with the condition, who were either treated with prednisone or with a combination of prednisone and cyclosporine for 18 months. Trial goals included changes in dyspnea (shortness of breath), pulmonary function as measured by forced vital capacity (FVC, the total volume of air that can be forcibly exhaled after a full inspiration), and sarcoidosis stage as measured by chest radiography. Results, published in 1997, showed no significant differences between the two treatment groups and more frequent severe side effects — and a doubling of infection rates — in the combination therapy group. “Although CsA [cyclosporin A] may have theoretical benefits in the treatment of sarcoidosis, our results do not support its use in this disease,” the study’s researchers concluded.

Additional information

Use of cyclosporine is associated with an increased risk of infection and cancer. Exposure to sunlight should be avoided during treatment to reduce the risk of skin cancer.

Cyclosporine can cause high blood pressure and kidney damage, and people with a history of either condition should notify their doctor before beginning cyclosporine use. The doctor can decide if an alternative treatment should be used.

Cyclosporine use is reported to have a number of potential side effects, including headaches, diarrhea, heartburn, flushing, muscle or joint pain, cramps, ear problems, and depression. It can also have more serious side effects, such as unusual bleeding, seizures, loss of consciousness, changes in behavior, and difficulties in controlling body movement. For a comprehensive list, patients should refer to the package insert that accompanies the medication or ask their doctor.

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