Combination Therapy for Rheumatoid Arthritis


Chris Iliades, MD

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There is no drug that can cure rheumatoid arthritis (RA), but there are many drugs to treat it. Doctors are discovering that the best way to ease swelling, improve movement, and reduce damage caused by RA is to treat it early and aggressively. This could mean taking more than one RA drug at the same time. This is called combination therapy.

Recent studies show that using combination therapy for newly diagnosed and active RA may be better than using one drug alone. In one study, doctors found that for people with early, active, and moderate to severe RA, using two drugs was more likely to control RA symptoms and prevent joint damage than using only one drug.

If you have early and active RA, combination therapy may be the best way to get your RA under control and stop your symptoms. This is called putting your disease into remission.

Drugs Used in Combination Therapy

There are four basic types of drugs used to treat RA:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to relieve pain and swelling quickly.

  • Corticosteroids are quick-acting and powerful drugs that block and decrease swelling (inflammation) in RA.

  • Disease-modifying anti-rheumatic drugs (DMARDs) are stronger than NSAIDs and are used to slow down the progression of RA. They take a few weeks to start working. DMARDs may be prescribed in order to reduce corticosteroid dosage and steroid-related adverse effects,

  • Biologic response modifiers (biologic DMARDs) are drugs that may be used when regular DMARDs are not working. Some of these drugs are also called anti-TNF drugs because they block tumor necrosis factor (TNF), a substance in your blood that causes inflammation and joint damage.

NSAIDs and steroids may be combined with any type of RA treatment to get a quick response. When doctors talk about combination therapy, they are talking about the best combination of DMARDs or biologic DMARDs for your long-term treatment of RA.

Finding the Right Level of Combination Therapy

Your RA will respond differently than other people’s RA. No combination therapy is right for everyone. If your RA is mild, you may start out with only one drug. If your doctor decides to use combination therapy, one of the drugs will probably be the DMARD methotrexate.

Methotrexate is used as the first drug in combination treatment because it works well in many people. It also causes fewer side effects than many other RA drugs. Methotrexate is the DMARD that most people with RA stay on the longest.

The American College of Rheumatology has these guidelines for combination therapy:

  • Two-drug DMARD therapy may be used if you have moderate to severe RA. The recommended combination is methotrexate and hydroxychloroquine. Hydroxychloroquine is a drug that also works for malaria. Doctors are not sure how it works in RA.

  • Three-drug DMARD therapy may be used if your RA is moderate to severe and your doctor is worried about long-term damage from RA. A common combination is methotrexate, hydroxychloroquine, and sulfasalazine. Sulfasalazine is not as strong as methotrexate but seems to work well when combined with methotrexate.

  • Methotrexate and an anti-TNF drug may be used if you have severe RA and have never been on a DMARD before. Anti-TNF drugs include etanercept, infliximab, certolizumab, golimumab and adalimumab. Anti-TNF drugs need to be given by injection or infusion (through an IV).

Side Effects and Long-Term Use

All RA drugs have side effects. Side effects from DMARDs may include liver damage, lung damage, and decreased resistance to infection. These drugs may not be safe during pregnancy.

Using more than one drug in combination therapy does not seem to cause more side effects, but doctors are still studying the long-term effects. If your doctor prescribes a combination therapy for you, see him or her for frequent follow-up visits. You may need to have blood tests to make sure you are not having a reaction to the drugs. Talk with your doctor about all the risks and benefits of combination therapy for RA.

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Medical Reviewers: William C. Lloyd III, MD, FACS Last Review Date: Apr 22, 2017

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Medical References

  1. Combating High Disease Activity in Early RA. Arthritis Foundation.
  2. Rheumatoid Arthritis Treatment. Johns Hopkins Arthritis Center.
  3. Combination Therapy for Rheumatoid Arthritis. National Rheumatoid Arthritis Society.
  4. Rheumatoid Arthritis. American College of Rheumatology.
  5. Rheumatoid Arthritis - Treatment. University of Maryland Medical Center.

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