Last updated: Aug 12, 2011

What is a DMARD? A DMARD, or disease-modifying antirheumatic drug, is anything used to treat rheumatoid arthritis (RA) that can slow down or prevent joint damage, as opposed to just relieve pain or inflammation.

DMARDs can "fundamentally change the process of how the disease attacks the body," says Eric L. Matteson, MD, chair of rheumatology at the Mayo Clinic, in Rochester, Minn.

There are a variety of DMARDS and they can be divided into two groups: older, conventional synthetic drugs or the newer biologics, which are genetically engineered versions of antibodies or proteins that can neutralize harmful inflammation in the body. There are pros and cons to each drug, and one that works well may eventually stop working, and you may need to switch.

Or, the side effects of one drug may prompt a switch to another.

Prescribing the right medication for a patient can be a trial-and-error process, but "in principle every patient should be on a DMARD because thats the best chance of getting the disease under control," says Dr. Matteson.

Here is a selection of DMARDs you may encounter during treatment for RA.

Abatacept

Brand name: Orencia
Type: Biologic

How you take it: Intravenous infusion (administered into a vein using an intravenous, or IV, drip), with the second and third doses administered each two weeks after the last, then once a month.

What you need to know: Abatacept, approved at the end of 2005, is one of the newer biologics. It contains a synthetic protein that interferes with the immune system cells, known as T cells. By reducing the activity of these T cells, abatacept lessens inflammation and joint damage. "It interferes with the way cells talk to each other," Dr. Matteson explains. The drug usually starts to work within three months.

Possible side effects: During the infusion: headaches, chills, light-headedness, nausea, shortness of breath. After the infusion: headache, upper respiratory infection, sore throat, nausea.

Adalimumab

Brand name: Humira
Type: Biologic

How you take it: Self-administered subcutaneous (under the skin) injection every other week. Dose and frequency can be increased to every week if the initial response is inadequate.

What you need to know: Adalimumab is one of five tumor necrosis factor (TNF) inhibitors approved by the FDA to treat rheumatoid arthritis. TNF is a type of cell-signaling molecule known as a cytokine which is "important in inflammation," Dr. Matteson explains. It causes damage by attracting immune cells to the area of the joints. This drug works well and relatively quickly but should not be used in patients who have multiple sclerosis, Dr. Matteson says.

Possible side effects: Localized allergic reaction to the shot, fever, chills, chest pain, shortness of breath, itching, headache, nausea, flushing in the face, rash, fatigue, dizziness. TNF blockers can increase the risk of serious infections, cancers such as lymphoma, blood and nervous system disorders, and liver injury.

Anakinra

Brand name: Kineret
Type: Biologic

How you take it: Self-administered subcutaneous injection usually once a day.

What you need to know: This is the only rheumatoid arthritis drug that works by inhibiting the cytokine known as interleukin (IL-1). Like TNF, IL-1 wreaks havoc by promoting inflammation in the joint, and it may play an important role in joint destruction. Anakinra usually starts working in two to four weeks.

Possible side effects: Allergic reaction at the injection site that usually goes away after one to two months, nausea, diarrhea, headache, infections, lower neutrophil (white blood cell) counts.

Antimalarials

Brand name: Hydroxychloroquine (Plaquenil) or chloroquine (Aralen)
Type: Conventional/small molecule

How you take it: Pill

What you need to know: These drugs were first used for malaria but also work well for various forms of rheumatoid arthritis, Dr. Matteson says. Generally they work for mild disease and are used in combination with other DMARDs, he adds. No one knows exactly how they work in patients but theyre thought to reduce symptoms by acting on the immune system in some way. Antimalarials usually start working in two to four months.

Possible side effects: Abdominal cramps, blurred vision, diarrhea, headache, increased sun sensitivity, rash, itching, loss of appetite, nausea and/or vomiting, dizziness, possible eye damage, kidney problems in rare cases.

Azathioprine

Brand names: Imuran, Azasan
Type: Conventional/small molecule

How you take it: Pill

What you need to know: Azathioprine dampens immune system activity, which reduces inflammation and damage to the joints. It is usually reserved for severe or life-threatening forms of RA that do not respond to other therapies. It can take 8 to 12 weeks to work.

Possible side effects: Chills, muscle aches, fatigue, fever, loss of appetite, liver problems, nausea, vomiting, diarrhea, weakness. More rare side effects include low blood counts, liver and pancreas damage, and malignancies such as skin cancer lymphoma. Patients taking azathioprine are monitored to make sure their blood cell counts do not drop too low.

Certolizumab

Brand name: Cimzia
Type: Biologic

How you take it: Subcutaneous injection usually every two weeks, given either by a nurse or the patient.

What you need to know: Approved for RA in 2009, certolizumab is another TNF blocker, meaning it interferes with a molecule involved with inflammation. "It is a little different, not necessarily better, than the other four TNF blockers," says James R. ODell, MD, professor of internal medicine and chief of rheumatology at the University of Nebraska Medical Center, in Omaha. It is "unique in that it is hooked to polyethylene glycol, PEG for short,” he says. “This helps it last longer.” It usually works within two to four weeks and achieves its peak effect within three months.

Possible side effects: Like other TNF blockers, the main concerns are infections such as tuberculosis and certain types of cancer such as lymphoma, Dr. O'Dell says.

Cyclophosphamide

Brand name: Cytoxan
Type: Conventional/small molecule

How you take it: Pill or IV injection

What you need to know: Like azathioprine, cyclophosphamide suppresses the immune system and is used for only the most severe cases of rheumatoid arthritis because of its potentially severe side effects and requirement for close patient monitoring.

Possible side effects: Blood in urine, darkening of skin and fingernails, hair loss, loss of appetite, low blood counts, amenorrhea (missed menstrual periods), nausea, vomiting, infertility and reduced sperm count in men, ovarian failure, bladder damage, bladder cancer. Despite the risk of infertility, it is still possible to become pregnant while taking cyclophosphamide; patients should use birth control to avoid this. The medication is not safe to take during pregnancy.

Cyclosporine

Brand names: Neoral, Sandimmune, Gengraf
Type: Conventional/small molecule

How you take it: Pill or liquid

What you need to know: Cyclosporine suppresses the immune system by inhibiting the cytokine interleukin-2 (IL-2) and thereby stifling the activity of T cells, which play an important role in RA. It is not advised that patients stay on cyclosporine for more than one year, and only then if their RA symptoms are acute, because of the potentially serious side effects and the need for careful monitoring.

Possible side effects: Abdominal pain, nausea, vomiting, headaches, loss of appetite, numbness, tremors, tingling, fever, chills, increased hair growth, gingivitis in rare cases. More serious side effects are high blood pressure, kidney problems, anemia, infection, and lymphoma. This drug can interact with numerous other medications.

Etanercept

Brand name: Enbrel
Type: Biologic

How you take it: Self-administered subcutaneous injection once a week (twice weekly doses are also available).

What you need to know: Etanercept is another TNF inhibitor that tends to work relatively quickly (one to four weeks) and with fewer potentially serious side effects than some of the other DMARDs.

Possible side effects: Allergic reaction such as itching or redness at the injection site, chest pain, headache, nausea, vomiting, as well as potentially serious side effects including fever, chills, shortness of breath, flushing in the face, fatigue, dizziness. Etanercept may also increase the risk of other serious toxicities including infections (though in most cases they are mild), blood or nervous system disorders, and cancers such as lymphoma.

Golimumab

Brand name: Simponi
Type: Biologic

How you take it: Once-a-month subcutaneous injection, which can be given by the patient using an auto-injector or a prefilled syringe.

What you need to know: Golimumab is another TNF inhibitor, which RA patients use in conjunction with methotrexate. Again, it blocks the pathway that can lead to the painful inflammation that is the hallmark of RA.

Possible side effects: The U.S. Food and Drug Administration has warned of the risk of serious fungal infections associated with TNF blockers. Children and teenagers taking TNF blockers may have a heightened risk of lymphoma and other cancers.

Gold salts (also known as auranofin)

Brand name: Ridaura
Type: Conventional/small molecule

How you take it: Pill

What you need to know: No one is sure how it works but slow accumulation over time may decrease inflammation. Dating from the 1920s, this was the original DMARD but "its not very effective," says Dr. Matteson. Rosalind Russell, a 1940s movie star and one of the most famous people with RA, is reported to have suffered bad side effects from taking gold salts. "I have not written a prescription for gold in more than 15 years," Dr. Matteson says.

Dr. ODell says, "Its a cumbersome therapy to use, there are significant toxicities, and it requires careful laboratory monitoring." That said, it does work for a handful of patients and is reasonably priced—so it does still play a role, albeit a small one. It takes three to four months to take full effect.

Possible side effects: Itching, rash, nausea, diarrhea, vomiting, decreased appetite, heartburn, headache, sensitivity to the sun, metallic taste, mouth sores, kidney damage, and, in rare cases, lower blood cell count and damage to bone marrow.

Gold sodium thiomalate

Brand names: Myochrysine, Aurolate, Solganal
Type: Conventional/small molecule

How you take it: Intramuscular injection weekly at first, then at reduced frequencies if efficacy is seen.

What you need to know: Like its cousin in pill form, no one is quite sure how this compound works except that accumulation in the body may reduce inflammation associated with rheumatoid arthritis. Injections seem to be more effective than pill and were the DMARD of choice until the 1990s when they were replaced with methotrexate. Both gold pills and injections have more side effects and neither is used very much any more, Dr. ODell says.

Possible side effects: Itching, rash, sores in mouth and throat, sore tongue, metallic taste, bleeding gums, abdominal discomfort, nausea, sore throat, unusual tiredness or weakness, joint pain one to two days after injection.

Infliximab

Brand name: Remicade
Type: Biologic

How you take it: Intravenous infusion typically every four to eight weeks. Dose and frequency of the infusion can be increased if relief isnt seen. Each infusion takes about two hours.

What you need to know: By dampening the activity of tumor necrosis factor, infliximab also reduces inflammation and thus the symptoms and progressive damage of rheumatoid arthritis. The drug should be given in combination with methotrexate, and results can be seen in days or weeks.

Possible side effects: Headache, nausea, and potentially more serious side effects such as fever, chills, chest pain, shortness of breath, fatigue, itching, rash, flushing in the face. Like the other TNF inhibitors, infliximab may also elevate the risk of serious infection and blood or nervous system disorders that lead to numbness and tingling, and cancers such as leukemia. In rare cases, it may also cause serious liver problems.

Leflunomide

Brand name: Arava
Type: Conventional/small molecule

How you take it: Pill, often starting with a larger "loading" dose because the medicine needs to build up in the body, followed by a smaller dose given daily.

What you need to know: Leflunomide blocks the production of the white blood cells that cause joint inflammation. It can be used as an alternative to methotrexate, as it works much the same way. Relief is often seen in four to eight weeks. However, the drug definitely should not be taken by women who are pregnant or planning to become pregnant, as it can cause birth defects.

Possible side effects: Diarrhea is most common, as well as heartburn, nausea, vomiting, headache, hair loss, rash, elevated blood pressure, sneezing, sore throat, bloody urine, liver problems, low blood cell counts, and neuropathy (loss of sensation in the feet or hands due to nerve damage). More potentially serious adverse effects include increased risk of infections, liver damage, and reactions to live vaccines.

Methotrexate

Brand names: Rheumatrex, Trexall
Type: Conventional/small molecule

How you take it: Orally

What you need to know: This drug, which is also used in higher doses in cancer treatment, "has been used in the treatment of rheumatoid arthritis for over 30 years and its still the mainstay of treatment," says Dr. ODell. "Its the most important disease-modifying drug we have."

Methotrexate appears to interfere with TNF and is one of the fastest-acting DMARDs, usually taking effect in four to six weeks. If a patient hasnt achieved close to a full remission in three to six months, another drug would be added, says Dr. ODell. Again, women who are pregnant or planning to get pregnant should not take the drug because it can cause miscarriages, he adds.

Possible side effects: Nausea and vomiting are the most common side effects, as well as diarrhea, fatigue, flu-like symptoms, chills, headache, hair loss, increased sensitivity to the sun, itching, shortness of breath, bacterial infections, and liver damage. Some of these side effects can be prevented by taking folic acid.

Minocycline

Brand names: Dynacin, Minocin, Myrac
Type: Antibiotic

How you take it: Pill

What you need to know: Minocycline is a tetracycline antibiotic that is normally used to fight bacterial infections. Although its not entirely clear how it works in patients who have rheumatoid arthritis, it may reduce the activity of proteins that damage cartilage—perhaps not very effectively, though. "It doesnt work very well and we dont really recommend it," Dr. Matteson says.

Possible side effects: Nausea, dizziness, diarrhea, changes in skin color, increased sensitivity to the sun, rash, headache, chronic hepatitis or liver inflammation, lupus in rare cases.

Penicillamine

Brand name: Cuprimine, Depen
Type: Conventional/small molecule

How you take it: Pill

What you need to know: Penicillamine is more often used as a last resort, for patients who have not responded to other DMARDS. It is more widely used to bind to and remove metals and toxic chemicals from the blood. It can take six months to be effective. Penicillamine has many of the toxicity drawbacks of gold and, says Dr. ODell, "is not used very much anymore by anybody."

Possible side effects: Nausea, vomiting, diarrhea, rash, mouth sores, decreased sense of taste or smell. Other serious, albeit rare, side effects include infection, kidney problems, low blood cell counts, muscle weakness, bleeding and bruising, increased risk of lupus, and birth defects during pregnancy.

Rituximab

Brand name: Rituxan
Type: Biologic

How you take it: Two intravenous infusions given two weeks apart. The infusions take several hours. Theres a lack of agreement as to when additional infusions should be given.

What you need to know: Rituximab is a monoclonal antibody that removes B cells (a type of white blood cell) from the blood stream. Although the two initial infusions can take up to three months to have an effect, they can give relief for between six months and two years. Its another drug "borrowed from oncology," Dr. ODell says, as its also used to treat lymphoma.

Possible side effects: Fever and chills usually within the first couple hours after the infusion, nausea, vomiting, skin rash, headache, sore throat, flushing. In rare cases, rituximab leads to serious infection, heart problems, and difficulty breathing, and for these reasons, people on the drug are closely monitored. People who have existing heart damage or who have hepatitis B need to be extra carefully monitored as rituximab can aggravate both of these conditions.

Sulfasalazine

Brand name: Azulfidine, Azulfidine EN-Tabs, Sulfazine
Type: Conventional/small molecule

How you take it: Pill

What you need to know: People who have sensitivity to aspirin and sulfa medications, including antibiotics such as Septra and Bactrim, should be careful when taking sulfasalazine. Although it is not clear how sulfasalazine works, the medicine can be almost as effective as methotrexate, and is given in combination with methotrexate in some cases to boost each drugs effect. It can take from six weeks to three months to take effect.

Possible side effects: Diarrhea, headache, nausea, vomiting, increased sensitivity to the sun, muscle and joint pain, itching, rash.

Tocilizumab

Brand name: Actemra
Type: Biologic

How you take it: Intravenous infusion every four weeks, and each treatment takes about one hour.

What you need to know: This is the newest member of the DMARD family, approved by the FDA in 2010. It works by interfering with yet another cytokine, interleukin 6 (IL-6). It is used when TNF inhibitors have been tried and failed, and it can be used alone or with other DMARDs.

Possible side effects: Dizziness, headache, sore throat, runny nose, sneezing, rash, itching, difficulty breathing, fatigue.