Cytotoxic Drugs for Rheumatic Diseases

Cancer drugs provide anti-inflammatory effect in rheumatic diseases

Pharmacist in the oncology pharmacy prepares Adriamycin (doxorubicin) for cancer patients to take intravenously. Credit: Michelle Del Guercio / Getty Images

Cytotoxic medications typically used to treat rheumatic diseases include:

  • Azathioprine (Imuran)
  • Cyclophosphamide (Cytoxan)
  • Methotrexate (Rheumatrex or Trexall)

These drugs were labeled "cytotoxic" because they treat malignancies by directly killing tumor cells. Their ability to help the signs and symptoms of other diseases, such as rheumatoid arthritis, lupus and vasculitis may, however, be due to their anti-inflammatory effects as opposed to their ability to kill cells. In fact, the low dosage of methotrexate used to treat these conditions is actually anti-inflammatory and not cytotoxic.

Benefits and Risks of Cytotoxic Drugs for Rheumatic Diseases


Of these three drugs, Cytoxan has the most potential side effects and is typically limited to treating moderate to severe cases of lupus, vasculitis, or lung disease that are sometimes associated with rheumatoid arthritis, myositis, and scleroderma.

The major concern with Cytoxan is the risk of bone marrow depression that may increase the risk of infection or bleeding. In addition, there is a small but definite increased risk of cancer involving the skin and bladder. Some patients may develop a very painful condition of the bladder called interstitial cystitis. If the drug is given orally, frequent water intake and urination may help prevent this problem. Cytoxan is often given by monthly intravenous infusions which may also help.

The drug is teratogenic (may cause birth defects if taken during pregnancy) and should be avoided in women who are not using effective birth control or who may be pregnant. Finally, there may be an increased risk for serious infection with Cytoxan use.


Imuran is FDA-approved for rheumatoid arthritis and is used to treat lupus and other connective tissue diseases. It is also associated with a risk of bone marrow depression and may slightly increase the risk of some cancers. There is an increased risk of getting a serious infection when taking this drug.


Methotrexate is FDA-approved for rheumatoid arthritis and may also be helpful for other connective tissue diseases such as lupus, myositis, and vasculitis.

While methotrexate can have the same potential side effects as the other two drugs, it appears to have a better safety profile. Similar to Cytoxan, it is teratogenic and should not be used by women and their partners if they are not using effective birth control or there is a chance of pregnancy.

In addition, the drug is associated with a small risk of lung disease (interstitial pneumonitis) that can be life-threatening if a patient doesn't stop the drug and get treated. Typically, symptoms of this problem include shortness of breath, dry cough, and fever. Like the other two medications, there may be an increased risk of serious infection.