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Immunosuppressives and Lupus

Immunosuppressive agents are generally used to reduce rejection of transplanted organs. They are also used in serious, systemic cases of lupus in which major organs such as the kidneys are affected or in which there is severe muscle inflammation or intractable arthritis.

Because of their steroid-sparing effect, immunosuppressives may also be used to reduce or sometimes eliminate the need for corticosteroids, thereby sparing the patient from undesirable side effects of corticosteroid therapy.

Immunosuppressives can have serious side effects. Patients need to understand, however, that side effects are dose-dependent and are generally reversible by reducing the dose or stopping the medication.

Types of Immunosuppressives

A variety of immunosuppressive drugs is available to treat lupus. Although they have different mechanisms of action, each type functions to decrease or prevent an immune response.

The immunosuppressives most frequently used with SLE patients are:

  • azathioprine (Imuran®): Azathioprine, one of the most widely used immunosuppressives for lupus, is an antimetabolite. Antimetabolites work by blocking metabolic steps within immune cells and then interfering with immune function. Used to control the underlying disease process, azathioprine has fewer serious side-effect risks than some other drugs used to control lupus.
  • cyclophosphamide (Cytoxan®). An alkylating agent and strong immunosuppressive, cyclophosphamide is reserved for treating lupus with kidney disease or other internal organ involvement. It works by targeting and damaging autoantibody-producing cells, thereby suppressing the hyperactive immune response and reducing disease activity. It has the potential for severe side effects, including risk of serious infection.
  • methotrexate (Rheumatrex®). Originally developed as a cancer treatment and later approved for rheumatoid arthritis, methotrexate, like azathioprine, is an antimetabolite. It is predominantly used for lupus arthritis. It requires monitoring of the CBC and liver function tests. To reduce toxicity, daily folic acid is prescribed.
  • cyclosporine (Neoral®).Originally developed to prevent the body from rejecting transplanted organs, cyclosporine is now commonly used to treat rheumatic diseases, including lupus. Cyclosporine is an antimetabolite.
  • mycophenolatemofetil (CellCept®). A strong immunosuppressive drug developed to prevent the rejection of transplanted organs, mycophenolate is sometimes used as an alternative to cyclophosphamide for lupus with kidney involvement. Mycophenolate works by keeping T and B lymphocytes from replicating.

There are many serious risks associated with the use of immunosuppressives. They include immunosuppression (resulting in increased susceptibility to infection), bone marrow suppression (resulting in decreased numbers of RBCs, WBCs, and platelets), and development of malignancies.

Possible Side Effects

  • Dermatologic: alopecia (cyclophosphamide and methotrexate)
  • Gastrointestinal: nausea, vomiting, stomatitis, esophagitis, and hepatotoxicity
  • Genitourinary: hemorrhagic cystitis, hematuria, amenorrhea, impotence, and gonadal suppression (cyclophosphamide only)
  • Hematologic: thrombocytopenia, leukopenia, pancytopenia, anemia, and myelosuppression
  • Respiratory: pulmonary fibrosis
  • Other: increased risk of serious infections or malignancies
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