Cytotoxic Drugs for Rheumatic Disease Treatment

Tempering Inflammation With Chemotherapy Drugs

Most commonly used in chemotherapy to shrink tumors and kill cancer cells, cytotoxic drugs are also used to treat rheumatic diseases, such as rheumatoid arthritis (RA).

Cytotoxic drugs such as Cytoxan (cyclophosphamide), Imuran (azathioprine), and methotrexate work by slowing cell production and decreasing inflammation.

When used for treating rheumatic disease, these medications are prescribed at lower doses than when they are used for cancer treatment, so that their roles are primarily anti-inflammatory. By modifying the body's immune and inflammatory actions, these medications reduce the symptoms caused by certain rheumatic diseases.

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Use in Rheumatic Disease

Rheumatic diseases include more than 200 conditions that cause chronic pain of the joints and/or connective tissues. Some rheumatic conditions (such as osteoarthritis and tendinitis) are caused by injury and everyday wear-and-tear, while others are autoimmune in nature.

Cytotoxic drugs are useful for treating autoimmune inflammatory diseases. The drugs treat autoimmune disorders by inhibiting the growth and action of certain immune cells that damage joints.

In RA, the body attacks its own cells and triggers inflammation and chronic pain of the tendons, ligaments, bones, or muscles of a joint.

Autoimmune rheumatic diseases that are sometimes treated with cytotoxic drugs include:

Treatment Options

When used at lower doses, cytotoxic drugs function as immune suppressants and can be classified as disease-modifying anti-rheumatic drugs (DMARDs). These drugs are commonly used to treat symptoms of pain and inflammation, as well as halt disease progression.

These medications are slow-acting and can take several weeks to have an effect on your system. Your healthcare provider may prescribe other medications to relieve symptoms of a flare-up while you wait for DMARDs to take effect.

Cytotoxic drugs can have unpleasant side effects and carry risks of organ damage and birth defects. In addition, these drugs can cause bone marrow suppression, resulting in low red blood cell counts (anemia), low white blood cell counts (leukopenia), and/or low platelets (thrombocytopenia), which can raise the risk of complications like bleeding and infections (including pneumonia and shingles).

Cytoxan, Imuran, and methotrexate modify the immune system as a whole, offering both benefits and risks to the user. Before prescribing a cytotoxic drug, your healthcare provider will carefully consider the potential benefits versus based on your individual health.

In addition, your healthcare provider will monitor your liver enzymes, kidney function, blood counts, and blood pressure when you are using these medications.


Methotrexate, which is available in both a pill and injectable form, is the first-line treatment for RA and is also commonly used to treat lupus, vasculitis, juvenile idiopathic arthritis, and other forms of inflammatory arthritis. 

Methotrexate is usually taken as a single dose once weekly but may be split into multiple doses to reduce side effects or increase absorption. Improvement generally begins within six weeks but may take up to 12 weeks.

Some users experience mouth sores, stomach upset, hair loss, rash, nausea, or diarrhea. Methotrexate can cause liver impairment, which means that you need frequent monitoring of your liver enzymes and avoidance of alcohol in all forms.

Your healthcare provider will likely prescribe a folic acid supplement to decrease the risk of some side effects of the drug.

Methotrexate is contraindicated during and months before pregnancy due to the increased risk of birth defects. Men and women should discontinue methotrexate for at least three months before trying to conceive. During this time, it is important to use condoms and other contraceptive methods to avoid pregnancy.

Cytoxan (Cyclophosphamide)

Cytoxan has a high potential for causing side effects. It destroys rapidly reproducing or growing cells in the body. As such, it is typically used to treat life-threatening autoimmune diseases when other DMARDs fail. This includes rheumatic diseases that seriously affect renal (kidney) or pulmonary (lung) function, including lupus, polymyositis, and scleroderma. It is also sometimes used to treat severe RA.

Cytoxan can be taken as a once-daily oral dose or given intravenously (IV, in a vein) every week or month. The dose varies depending on your body weight and the condition being treated.

Cytoxan is often prescribed for three to six months to achieve disease remission; a less-potent drug is then prescribed to avoid relapse.

Common side effects include nausea, vomiting, and hair loss (hair typically returns once the treatment is stopped). Cytoxan may cause birth defects and is contraindicated during pregnancy and for couples trying to get pregnant.

Live vaccines should be avoided while taking Cytoxan. Precautions should be taken if any household members receive any live vaccines. Your healthcare provider may recommend updating your vaccinations prior to starting the drug.

Imuran (Azathioprine)

Imuran treats autoimmune conditions by interfering with the formation of DNA molecules. Most commonly used to prevent autoimmune triggered organ rejection following transplant surgery, this drug is also approved for the treatment of RA, lupus, polymyositis, and vasculitis.

Imuran comes as a tablet taken once or twice a day. Your healthcare provider may start you at a low dose for several weeks to see how you tolerate the medication prior to increasing it to a dose that is effective for you.

Imuran may increase your risk of liver or pancreas damage and certain cancers. Your healthcare provider will closely monitor your blood counts, liver enzymes, and blood sugar while taking Imuran.

Side effects include stomach upset, nausea, and other gastrointestinal symptoms. These may be relieved by dividing the daily dose into two separate doses, with one taken in the morning and the other taken at night.

Talk to your healthcare provider before receiving any vaccines or undergoing any surgeries while you are taking Imuran.

A Word From Verywell

Cytotoxic drugs have their places in the treatment of rheumatic diseases. Because they work by dampening the immune system as a whole—meaning that you have fewer defenses to fight disease—you need to contact your healthcare provider immediately if you ever experience signs of an infection, like fever, cough, chills, shortness of breath, rash, or bleeding while on one of these drugs.

Methotrexate and Imuran can be used for long-term therapy, provided there are not substantial side effects from the drugs. Cytoxan, on the other hand, is generally used for a shorter period of time because of the more intense side effects. Used as prescribed, cytotoxic drugs can greatly reduce the symptoms of severe RA and other rheumatic diseases, allowing you to maintain a healthier, more active lifestyle.

10 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Carol Eustice
Carol Eustice is a writer covering arthritis and chronic illness, who herself has been diagnosed with both rheumatoid arthritis and osteoarthritis.