Treating Rheumatoid Arthritis With Disease-Modifying Drugs (DMARDs)

Medically Reviewed by Melinda Ratini, MS, DO on October 28, 2021

Rheumatoid arthritis treatment includes medications that slow the progression of joint damage from rheumatoid arthritis. These drugs are called disease-modifying antirheumatic drugs (DMARDs), and they are an important part of an overall treatment plan. What are these drugs, and how do they work?

Disease-modifying drugs act on the immune system to slow the progression of rheumatoid arthritis. This is why they are called "disease-modifying." Many different drugs can be used as DMARDs in the treatment of RA, but some are used more often than others.

DMARD Side Effects and Use

Hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine) are used for mild rheumatoid arthritis. They are not as powerful as other DMARDs, but they usually cause fewer side effects. In rare cases, Plaquenil can adversely affect the eyes, and patients taking this medicine should be seen by an ophthalmologist at least once a year.

Leflunomide (Arava) works about as well as methotrexate and can work even better in combination with it. The side effects are similar to methotrexate. Sometimes, Arava causes diarrhea and can't be used. Since Arava is known to cause harm to a fetus, women must take special precautions to prevent pregnancy.

Methotrexate is the most commonly used DMARD. This is because it has been shown to work as well or better than any other single medicine. It is also relatively inexpensive and generally safe. Like other DMARDs, methotrexate has side effects; it can cause rash and stomach upset, can be toxic to the liver or bone marrow, and can cause birth defects. In rare cases, it can also cause shortness of breath. Regular blood work is necessary when taking methotrexate. Taking folic acid helps reduce some of the side effects. Methotrexate's biggest advantage could be that it has been shown to be safe to take for long periods of time and can even be used in children.

Minocycline (Minocin) is an antibiotic that is not often prescribed. But it may help RA by stopping inflammation. It can take several months to start working and up to a year before the full effects are known. When taken for long periods, minocycline can cause discoloration of the skin.

Biologic drugs:abatacept (Orencia and biosimilars), adalimumab (Humira and biosimilars), anakinra (Kineret), certolizumab (Cimzia), etanercept (Enbrel and biosimilars), golimumab (Simponi and biosimilars), and infliximab (Remicade and biosimilars). These are drugs for RA and are either injected under the skin or given directly into a vein. Most of these work by neutralizing one of the immune system's signals (TNF) that lead to inflammation and joint damage. Rituximab (Rituxan), sarilumab (Kevzara), tofacitinib (Xeljanz), and tocilizumab (Actemra) are biologics, but do not block TNF. Rituxan target B cells and Actemra and Kevzara affect IL-6. When used with methotrexate, these medicines help most people with rheumatoid arthritis. Some of these drugs are thought to have fewer side effects than other DMARDs. One side effect is the risk for potentially severe infections. These medicines can also, although rarely, adversely affect your liver or blood counts. Other potential long-term effects won't be known until the drugs have been used by patients for many years.

Azathioprine (Imuran) is used for many different inflammatory conditions, including RA. The most common side effects are nausea and vomiting, sometimes with stomach pain and diarrhea. Long-term use of azathioprine is associated with an increased risk of cancer.

Cyclosporine (GengrafNeoralSandimmune)is a powerful drug that often works well in slowing down joint damage. But because it can hurt the kidneys and has other potential side effects, it is usually used for severe RA after other drugs fail and is not in widespread use at this time.

Baricitinib (Olumiant)tofacitinib (Xeljanz) iand upadacitinab (Rinvoq) are drugs classified as JAK inhibitor. They are often used in people who no longer respond to methotrexate. Tofacitinib comes as a pill taken twice a day, while baricitinib or upadacitinib are taken once a day with or without food.  Because they inhibit immune responses, they adds to a person's risk of serious infections, cancers, and lymphoma. The drugs will carry a "black box" warning about these risks.

DMARDs slow down rheumatoid arthritis and improve quality of life for most people. Some will even achieve a remission while taking them. More commonly, the disease activity continues, but at a slower, less intense pace.

While taking one or more DMARDs, you may have longer symptom-free periods, or flare ups that are less painful or stressful. Your joints may take less time to loosen up in the morning. At a check-up, your rheumatologist may end up telling you that your most recent X-rays are free of any new damage. Taking a DMARD regularly makes you less likely to have long-term damage to your joints, too.

Are DMARDs Safe?

The FDA has approved all DMARDs. Many people take them without ever having problems.

But because they work throughout the body to fight RA, their powerful action typically does cause some side effects, commonly:

  • Stomach upset. DMARDs sometimes cause nausea, sometimes with vomiting, or diarrhea. Other medicines can help treat these symptoms, or they often improve as you get used to the drug. If the symptoms are too uncomfortable to tolerate, your rheumatologist will try a different medication.
  • Liver problems. These are less common than stomach upset. Your doctor will check blood tests on a regular basis to make sure your liver is not being harmed.
  • Blood problems. DMARDs can affect the immune system and raise the risk of infection. Infection-fighting white blood cells may also be decreased. Low red blood cells (anemia) can make you tired more easily. A simple blood test by your doctor every so often will make sure your blood counts are high enough.

You should learn about possible side effects of any medicine you are taking and discuss them with your doctor until you feel comfortable.

To minimize side effects, DMARDs are sometimes started one at a time and increased gradually. The goal is to minimize both rheumatoid arthritis disease activity and medication side effects. It often takes more than one DMARD to get control of active rheumatoid arthritis.

How do you know you're on the "right" regimen? There's no easy way. Rheumatologists use all their training and experience to determine what's right for you.

Though DMARDs can have side effects, there is a good reason to take them -- they're proven to work against rheumatoid arthritis. Even if you are in remission, many rheumatologists believe you should keep taking a DMARD, just to keep your RA at bay. There is also a likelihood of recurring disease when stopped altogether.

Show Sources


American College of Rheumatology Ad Hoc Committee on Clinical Guidelines, Guidelines for the management of rheumatoid arthritis: 2002 update, Arthritis and Rheumatism, 2002.

Harris, E., Kelley's Textbook of Rheumatology, 7th edition, W.B. Saunders, 2005. 

Klippel, John H., Primer on the Rheumatic Diseases, 12th edition, Arthritis Foundation, 2001. 

Maetzel A., Journal of Rheumatology, December 1998. Patient Drug Information. 

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