Facts About DMARDs (Disease-Modifying Anti-Rheumatic Drugs)

Remittive and slow-acting: both of these words describe how a class of drugs, commonly referred to as DMARDs (disease-modifying antirheumatic drugs), are used to treat rheumatoid arthritis. DMARDs, usually prescribed after less potent drugs are deemed ineffective, are also used to treat related inflammatory conditions, such as ankylosing spondylitis, psoriatic arthritis, and lupus.

The drugs are considered remittive because they can slow down the disease process, though seldom lead to a complete remission. Since it may take 6 to 8 months for the drugs to evoke a response, they are viewed as slow-acting drugs and are chosen as a second-line treatment option after aspirin and NSAIDs (nonsteroidal anti-inflammatory drugs) fail.

It is not exactly understood how DMARDs work. DMARDs appear to decrease inflammation, though they are not categorized as anti-inflammatory drugs. They are unlike NSAIDs since they do not decrease prostaglandin production and do not directly relieve pain or reduce fever. In effect, DMARDs slow the disease process by modifying the immune system in some way. Unlike NSAIDs, which temporarily reduce pain and inflammation, DMARDs can slow the progression of rheumatoid arthritis. People may have fewer symptoms and less damage over time.

The effectiveness, safety, side effects, and duration of use of DMARDs have been questioned by concerned patients. Studies throughout the years have shown DMARDs to be very effective drugs, with uncommonly observed serious side effects. Frequent laboratory monitoring helps control the risk of side effects. Once thought to be a short-term treatment, DMARDs are now regarded as a long-term solution for controlling symptoms and slowing disease progression.

Gold for Arthritis

Discovered accidentally by a French physician, gold salts have been used for the treatment of arthritis for over 50 years. Jacques Forrestier injected gold salts into a tuberculosis patient to treat the infection. The patient coincidentally had arthritis and after many months of treatment with gold, arthritis improved. Gold has been used to treat arthritis ever since.

The mechanism of how gold works is unclear, but apparently it interferes with functions of white blood cells responsible for joint damage and inflammation. Though gold may slow destruction, it cannot correct existing joint deformities.

Gold was originally available only as an injectable drug. Given on a continuous maintenance schedule, it requires routine blood and urine tests to be administered. In 1986, gold became available in an oral form with the trade name Ridaura. The most common side effects associated with injectable gold are an itchy rash on lower extremities and mouth ulcers which usually disappear when the medicine is stopped. Oral gold has fewer side effects but can cause transitory diarrhea or loose bowel movements. Gold seems to work extremely well for 10% of patients and very well for another 30-40%. Fifty percent of patients discontinue use due to side effects or ineffectiveness.

The use of gold has significantly decreased, especially with the development of biologic drugs. The first biologic, Enbrel, became available in 1998. Biologics are injectable drugs and are prescribed by physicians when DMARDs alone aren't working well enough to treat your symptoms.


Penicillamine, a distant relative of penicillin, became available in the 1970s. Penicillamine is known as a chelator because it can bind heavy metals in the body. Its mechanism of action in rheumatoid arthritis is not known, but it is thought to alter the function of white blood cells responsible for joint damage. It may become more active when it combines with copper, which is naturally present in the body.

Penicillamine is given orally, starting with a low dose, then by gradually increasing the dose. It is taken on an empty stomach at least one hour before or after meals. If effective, the patient must stay on this treatment course indefinitely. Side effects are similar to those associated with gold—skin rashes, mouth sores, loss of taste, and gastrointestinal upset. Protein in the urine can be an early sign of kidney damage.

Penicillamine can be used together with NSAIDs, though the NSAID should be taken during meals. Patients who are allergic to penicillin can still take penicillamine. It is effective in about 30% of patients.

Plaquenil (Hydroxychloroquine)

Plaquenil (hydroxychloroquine) has been available for many years and was originally used to treat malaria. It is simple to use, has few side effects, and does not require monitoring with blood tests. Plaquenil is used for patients with rheumatoid arthritis who do not respond well to NSAIDs. It seems to be effective in about 30% of patients. It is also used for patients with systemic lupus.

Plaquenil appears to interfere with immune cell function. The drug is given orally, in one or two tablets a day. One rare serious side effect is the deposit of the drug in the retina with the potential of visual impairment. An ophthalmology exam is recommended at least once a year. NSAIDs can be taken with Plaquenil and are often prescribed together.

Methotrexate (Rheumatrex)

Methotrexate, available for over 40 years, is widely used to treat psoriasis and is also used to treat cancer. In the 1970s, low-dose methotrexate was prescribed by many rheumatologists to treat rheumatoid arthritis when NSAIDs failed. Today, it is one of the most commonly used DMARDs. Methotrexate works faster than other remitting drugs, often bringing improvement in weeks rather than months. It is also inexpensive.

Methotrexate is an antimetabolite, interfering with the utilization of folic acid. It is thought to inhibit immune system activity and reduce inflammation. It also may slow the rapid growth of cells in the synovial membrane, which lines the joint.

Methotrexate can be given orally or as an injectable drug according to a strict dosage schedule. Some of the common side effects include rash and stomach upset. Along with the usual lesser side effects, serious side effects with methotrexate use can involve liver, lung, and kidney damage. Routine laboratory monitoring of liver and kidney function is required.

Methotrexate can be taken along with NSAIDs or biologics. Patients taking methotrexate are warned to avoid alcohol.


Sulfasalazine is a combination salicylate and antibiotic. It has been around since the 1940s, and was originally used to treat patients with inflammatory bowel disease. At one time, it was used to treat rheumatoid arthritis, but its use was limited because of concern over side effects. It has also been used in clinical trials as an alternative to gold. There was a period of renewed interest in its use as a remitting agent without the toxicity problems of gold and penicillamine.

The mechanism of sulfasalazine is unknown, though it has two potential actions, blocking inflammation and inhibiting the growth of bacteria. Sulfasalazine is available in tablet and liquid form. It should be avoided by people with allergies to sulfa drugs and/or aspirin and other salicylates. Common side effects include nausea, diarrhea, vomiting, and loss of appetite. More serious side effects are urine problems, blood diseases, and severe allergic reactions.

In choosing any particular drug to combat arthritis, you and your doctor must weigh the benefits and the risks of the treatment.

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  • The Duke University Medical Center Book of Arthritis, David S. Pisetsky, M.D.