Cytotoxic Drugs for Rheumatic Disease Treatment

Tempering Inflammation With Chemotherapy Drugs

Cytotoxic drugs are a class of drugs that slow the growth and action of certain types of cells. Most commonly used in chemotherapy to shrink tumors and kill cancer cells, cytotoxic drugs also treat rheumatic diseases such as rheumatoid arthritis (RA).

The cytotoxic drugs Cytoxan (cyclophosphamide), Imuran (azathioprine), and methotrexate work to treat RA and similar conditions by slowing cell reproduction and decreasing byproducts produced by the cells that cause inflammation.

The drugs are prescribed at lower doses than used for cancer treatment so that their roles are primarily anti-inflammatory. By tempering the body's response in this way, impairment caused by the disease can be reduced.

Use in Rheumatic Disease

Rheumatic disease is an umbrella term for more than 200 conditions that cause chronic pain of the joints and/or connective tissues. Some rheumatic conditions (e.g., osteoarthritis and tendinitis) are caused by injury or everyday wear-and-tear, while others are autoimmune in nature.

Cytotoxic drugs are specifically useful in the latter cases. The drugs treat autoimmune disorders by inhibiting the growth and action of certain immune cells that damage joints resulting in symptoms.

Rheumatoid arthritis is one such disorder that can be treated with cytotoxic drugs. In RA, the body attacks its own cells and triggers chronic pain and inflammation in the tendons, ligaments, bones, or muscles of a joint.

Other 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 build up in your system. Your doctor 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 and/or white blood cell counts (anemia, leukopenia) and low platelets (thrombocytopenia), which can raise the risk of bleeding and infections including pneumonia and shingles).

Cytoxan, Imuran, and methotrexate temper the immune system as a whole, offering both benefits and risks to the user. Before prescribing a cytotoxic drug, your doctor will carefully consider the potential benefits versus the risks for your individual disease path.

In addition, your doctor will monitor your liver enzymes, kidney function, blood counts, and blood pressure while taking these medications.


Methotrexate has long been the backbone of rheumatic disease therapy. Available in both a pill and injectable form, it is the first-line treatment for rheumatoid arthritis 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 is generally felt 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 and, as such, requires frequent monitoring of your liver enzymes and the avoidance of alcohol in all forms.

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

Methotrexate is contraindicated in pregnancy due to the increased risk of birth defects. Methotrexate treatment should be discontinued by both women and men for at least three months before trying to conceive. During this time, use condoms and other contraceptive methods to avoid pregnancy.

Cytoxan (Cyclophosphamide)

Of these three drugs, Cytoxan has the most potential for side effects. 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 rheumatoid arthritis.

Cytoxan can be taken as a once-daily oral dose or delivered by injection at the doctor's office 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 or in 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 doctor may recommend updating your vaccinations prior to starting the drug.

Imuran (Azathioprine)

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

Imuran comes as a tablet taken once or twice a day. Your doctor 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 doctor 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 doctor before receiving any vaccines or undergoing any surgeries while 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 doctor immediately if you ever experience fever, cough, chills, shortness of breath, rash, bleeding, or other signs of infection while on one of these drugs.

Used as prescribed, cytotoxic drugs greatly reduce the symptoms of rheumatoid arthritis and other rheumatic diseases, allowing you to maintain a healthier, more active lifestyle.

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  1. Woytala PJ, Morgiel E, Łuczak A, Czesak-woytala K, Wiland P. The Safety of Intravenous Cyclophosphamide in the Treatment of Rheumatic Diseases. Adv Clin Exp Med. 2016;25(3):479–84. doi:10.17219/acem/28736

  2. NIH: National Institute of Arthritis and Musculoskeletal and Skin Diseases. Arthritis and Rheumatic Diseases. Updated July 2019.

  3. UpToDate. Malignancy and Rheumatic disorders.

  4. Wilsdon TD, Hill CL. Managing the drug treatment of rheumatoid arthritis. Aust Prescr. 2017;40(2):51-58.

  5. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid ArthritisArthritis Rheumatol. 2016;68(1):1-26. doi:10.1002/art.39480

  6. American College of Rheumatology. Methotrexate (Rheumatrex, Trexall, Otrexup, Rasuvo). Updated March 2019.

  7. American College of Rheumatology. Cyclophosphamide. Updated March 2019.

  8. U.S. National Library of Medicine: MedlinePlus. Cyclophosphamide. Updated July 21, 2020.

  9. U.S. National Library of Medicine: MedlinePlus. Azathioprine. Updated July 21, 2020.

  10. American College of Rheumatology. Azathioprine. Updated March 2019.