Chemotherapy drugs are commonly used as cancer treatments due to their ability to kill cells that divide quickly, like cancer cells. However, chemotherapy drugs also can be used to treat people with autoimmune diseases like rheumatoid arthritis (RA).

If you have RA, it may be confusing to be prescribed a medication that’s typically used for cancer treatment. However, health care providers prescribe much lower doses of these medications to treat autoimmune diseases like RA. Here’s what you need to know about chemotherapy drugs and some of their common side effects when used to treat RA.

Which Chemotherapy Drugs Are Used for Rheumatoid Arthritis?

Chemotherapy drugs, along with advanced treatments like Janus kinase (JAK) inhibitors and biologics, used for rheumatological diseases are known as disease-modifying antirheumatic drugs (DMARDs). These drugs help slow the progression of autoimmune diseases and prevent further joint damage. DMARDs target the cause of inflammation, which usually results from the body’s immune system attacking healthy cells.

DMARDs help limit the number of immune cells made and the inflammatory signals they release. These medications are commonly called immunosuppressive drugs because they work by intentionally suppressing the immune system. DMARDs that are also considered chemotherapy drugs are given at lower doses to treat rheumatoid arthritis compared to when they’re used to treat cancer.

Methotrexate

Methotrexate (Otrexup, Rheumatrex, Trexall, Xatmep) is a first-line DMARD given to many people with RA. It’s used in much higher doses to treat some types of cancer. When used to treat RA, methotrexate is effective, has few side effects, and is easy to take. It can be given as a subcutaneous injection (just under the skin) or taken orally (by mouth), providing flexible dosing options for people with RA. Typically, methotrexate begins working within four to six weeks after treatment. The dose can be easily adjusted as needed.

Methotrexate may be combined with other RA medications for more effective treatment, including nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil) and naproxen (Aleve). Methotrexate may also be used in double therapy with another DMARD, such as:

• Azathioprine (Azasan, Imuran)
• Cyclosporine (Neoral, Sandimmune)
• Hydroxychloroquine (Plaquenil)
• Leflunomide (Arava)
• Sulfasalazine (Azulfidine)

You may have heard of triple therapy — a treatment regimen for RA that combines medications like methotrexate, sulfasalazine, and hydroxychloroquine. However, more recent treatment guidelines from the American College of Rheumatology don’t suggest using triple therapy for people with moderate to high RA disease activity. This is because doctors have found methotrexate works well on its own and doesn’t cause as many serious side effects.

Azathioprine

Azathioprine is an immunosuppressive drug used to treat RA and other autoimmune conditions. It’s also considered chemotherapy because it can be given at higher doses as part of a regimen to treat cancer. This DMARD works by preventing cells from making new DNA molecules so that they stop dividing and die. It can also be used to dampen the immune system before an organ transplant to prevent the new organ from being rejected.

Azathioprine is given orally as a tablet in doses between 50 and 250 milligrams, according to the American College of Rheumatology. You may notice that the medication begins working six to eight weeks after starting treatment, and it may take up to 12 weeks to feel the full effects.

Cyclophosphamide

Cyclophosphamide is an immunosuppressive medication used for treating severe RA that hasn’t responded well to other treatments (known as refractory RA). It can also be used for treating conditions associated with RA, such as vasculitis (inflammation of the blood vessels). Cyclophosphamide has serious risks, including infection and damage to cells in the bone marrow. To help avoid side effects, your doctor or rheumatologist will check your blood cell counts regularly while you’re taking this medication.

Cyclophosphamide can be given by injection at a hospital or doctor’s office every one to four weeks, or it can be taken orally. The dosage changes from person to person, but it’s typically based on body weight and height, as well as how well your kidneys work. It can take several weeks to see improvements and even longer to notice the full effects.

Other Medications

Some medications are often grouped together under the umbrella term “chemotherapy” when they’re part of cancer treatment, but they aren’t considered chemotherapy drugs when they’re used to treat RA. For example, corticosteroids (also known as steroids) may be considered as part of a chemotherapy plan for cancer. However, for treating RA, corticosteroids are given because they’re strong, fast-working, anti-inflammatory drugs. Corticosteroids mimic the shape and function of the body’s natural hormones that dampen the immune system.

Corticosteroids can be given in many ways, including by mouth or as intramuscular or intravenous injections. In some cases, corticosteroids can be injected directly into a joint to help treat joint pain at the source. Examples of corticosteroids include prednisone and methylprednisolone (Medrol).

Side Effects of Chemotherapy Drugs for Rheumatoid Arthritis

Chemotherapy drugs may come with several side effects. Most RA treatment plans using chemotherapy use a low dose of the drugs, and the side effects are usually less severe than when these drugs are given to treat cancers.

Methotrexate

Common side effects of methotrexate for RA include:

• Gastrointestinal problems like nausea, vomiting, and diarrhea
• Fatigue, sometimes called “methotrexate fog”
• Sores on the mouth, lips, or throat
• Hair loss, a less common side effect

Talk to your doctor if you experience any of these side effects — luckily, most can be prevented and managed. Your health care provider might suggest you take folic acid supplements to help reduce gastrointestinal problems and mouth sores or try other strategies to prevent and lessen side effects.

While you’re taking methotrexate for RA, your health care provider will run routine blood tests to check for signs of liver damage and changes in blood cell counts. Changes in blood cells and platelets could increase your risk of infections or cause bleeding. Methotrexate may also cause a cough or shortness of breath, which may be signs of lung inflammation or fibrosis.

Researchers have also found links between chemotherapy drugs and an increased cancer risk. This rarely happens with RA drugs such as azathioprine, cyclophosphamide, and methotrexate, but all three have been linked to lymphoma (a type of blood cancer). People with RA who take methotrexate are more likely to develop lymphoma if they’ve been infected with the Epstein-Barr virus.

Tell your doctor about any health changes you experience while taking methotrexate. They may have you take other medications or stop using methotrexate, depending on your situation.

Azathioprine

More common side effects of azathioprine include:

• Gastrointestinal issues such as nausea and vomiting
• Rashes
• Liver problems
• Mouth sores or a sore throat
• Increased risk of infections
• Birth defects in children born to people taking this medication

Talk to your health care provider to learn more about side effects and how to manage them. Nausea and vomiting may be eased by taking the drug after eating or dividing it into smaller doses, for example. Your health care provider will monitor you for more serious side effects, but you should always tell them if you develop new symptoms after starting medication.

Cyclophosphamide

Common side effects of cyclophosphamide include:

• Gastrointestinal problems such as nausea and vomiting
• Hair loss
• Rashes
• Increased risk of infections
• Infertility
• Bladder problems like blood in the urine

Talk to your rheumatology provider if you’re taking cyclophosphamide and experience any of these side effects. Problems such as nausea can be treated with anti-nausea medication. Side effects like hair loss should diminish when you finish taking the medication.

Tell your rheumatology provider about all your medications, including prescription and over-the-counter drugs. This information will help them avoid dangerous drug interactions and decide on the best treatment plan for your RA. Although side effects may seem intimidating, they might not occur and can be treated if they do. You may find that the benefits of RA treatment outweigh the risk of side effects.

Connect With Others Who Understand

On myRAteam, the social network for people with rheumatoid arthritis and their loved ones, more than 206,000 members come together to ask questions, give advice, and share their stories with others who understand life with RA.

Have you been given chemotherapy to treat your RA? How does it work for you, and what side effects have you experienced? Share your thoughts below, or by posting a comment on your Activities page.