Disease-modifying anti-rheumatic drugs, often referred to as DMARDs, are the second line of defense in treating rheumatoid arthritis. Years ago, DMARDs were not prescribed until it was evident that NSAIDs or a low dose of corticosteroids were not enough to slow disease progression. At that point, a DMARD was prescribed. Now, treating a rheumatoid arthritis patient aggressively in the early stages following diagnosis is thought to be important. DMARDs are now recommended early in the course of the disease in an attempt to slow disease progression.

It is possible to take more than one DMARD in certain cases, called combination therapy. Gold, penicillamine, plaquenil, sulfasalazine, and methotrexate were among the original DMARDs used to treat rheumatoid arthritis. In September 1998, another DMARD was FDA approved — Arava (leflunomide).

Gold

Gold as a treatment for arthritis was discovered by accident by a French doctor. The French doctor prescribed gold (as an injection) for a tuberculosis patient who also had arthritis. The patient received gold injections for many months as a tuberculosis treatment. The gold had an unexpected positive response for the patient's arthritis symptoms. Thereafter, gold was used to slow progression of rheumatoid arthritis. The drug could not reverse joint deformity that had already occurred though. Myochrysine (gold sodium thiomalate) and Solganol (aurothioglucose) are two forms of injectable gold salts that are available.

In 1986, gold became available in an oral formulation known as Ridaura (auranofin). About 50 percent of patients on gold had to stop using the drug due to side effects or lack of benefit. Itchy rash, mouth ulcers, and diarrhea, or loose bowels are common side effects of gold. Gold is now rarely initiated as a new therapy. At one point, gold was considered the “gold standard treatment” for moderate to severe rheumatoid arthritis; now, methotrexate is considered the gold standard treatment for rheumatoid arthritis.

Penicillamine

Penicillamine is a DMARD that became available in the 1970s. As its name suggests, the drug is somehow related to penicillin. The connection is not strong, since patients who are allergic to penicillin are still able to take penicillamine. The drug is reportedly effective in 30 percent of patients who try it.

Penicillamine is an oral drug that is initially given in low doses and built up gradually. It has similar side effects to gold, and is to be taken on an empty stomach at least one hour before meals.

Plaquenil

Originally used as a malaria treatment, plaquenil (hydroxychloroquine) is prescribed for rheumatoid arthritis patients and is also used to treat lupus. The drug is considered safe, with few side effects. An eye exam with an ophthalmologist is recommended every 6 to 12 months to check for a rare side effect which can occur with plaquenil — retinopathy. Plaquenil, which is taken orally as one or two pills a day, is effective for 30 percent of patients. It is still used by patients who for one reason or another are not candidates for some of the newer biologic DMARDs.

Sulfasalazine

Originally used to treat patients with inflammatory bowel disease, sulfasalazine has been on the market since the 1940s. Sulfasalazine (also known as azulfidine) is a combination drug of salicylate and an antibiotic. It is available as a liquid or tablet.

Sulfasalazine is used as a treatment for rheumatoid arthritis, but lost popularity because of bothersome side effects (nausea, diarrhea, vomiting, urine problems, blood diseases, and severe allergic reactions). Patients who are allergic to sulfa, aspirin, or other salicylates should not take sulfasalazine.

Methotrexate

Methotrexate was developed in the 1940s as a leukemia drug. Considered experimental in the 1970s, methotrexate was approved by the U.S. FDA to treat rheumatoid arthritis in 1988. In low doses, methotrexate is a weekly treatment for psoriatic arthritis, juvenile arthritis, vasculitis, lupus, and rheumatoid arthritis.

The usual starting dose is three to four (2.5 mg) pills a week (taken together on one day). The dose can be adjusted depending on the patient's response. Methotrexate is also available as an injectable drug, which is preferred by some patients who become nauseous or have an upset stomach after taking methotrexate tablets.

The benefit of taking methotrexate (brand names: Rheumatrex and Trexall) is usually evident in six to ten weeks for most patients. It may take twelve weeks for full benefit to be realized by some patients.

Arava

Arava is the newest of the nonbiologic DMARDs. Though Arava is thought to interfere with the formation of DNA, it's not clear how it works for rheumatoid arthritis.

Arava is usually prescribed as a 20 mg tablet to be taken once a day with food. Doctors may also prescribe a loading dose, where you initially take more of a drug for a specified period of time.

Results are slow to observe — it may take 6 to 12 weeks to notice the full benefit of using Arava. Side effects can occur: About 20 percent of patients on Arava have diarrhea. The problem can subside over time or with the help of antidiarrheal medicines. Indigestion, rash, and hair loss are also side effects of Arava, though they are less common. Abnormal liver function tests, and decreased blood cells or platelets have been observed in less than 10 percent of patients taking Arava.