Methotrexate is usually given as pills. Patients who need higher doses can take it as an injection. Methotrexate has fewer serious toxic effects than many DMARDs. Although these severe reactions are rare, they may include:

• Kidney and liver damage. People at particular risk for liver damage from methotrexate include those with diabetes, obesity, and alcoholism. Patients should limit alcohol consumption to no more than 2 drinks per month while taking this drug.
• Increased risk for infections. Methotrexate should not be given to patients with active bacterial infections, active herpes-zoster viral infection, active or latent tuberculosis, or acute or chronic hepatitis B or C.
• Lung disease occurs in some people. People who have poor lung function are most at risk.
• The drug increases the risk for birth defects and should not be taken by pregnant women. However, methotrexate will not harm a woman’s chance for future healthy pregnancy.

Leflunomide. Leflunomide (Arava, generic) blocks autoimmune antibodies and reduces inflammation. It also may inhibit metalloproteinases (MMP), which are involved in cartilage destruction. Leflunomide takes several weeks before improving joint pain or swelling. Full benefits may not occur until 6 - 12 weeks of treatment.

Leflunomide may be given alone or in combination with other DMARDs such as methotrexate (This combination poses a risk for liver toxicity and requires monitoring.)

Side effects are similar to those of methotrexate, including nausea, diarrhea, hair loss, and rash. Potentially serious side effects include infections and severe liver injury. Everyone taking leflunomide should be monitored regularly, including blood tests for liver function, and anyone with liver problems should not take this drug. Leflunomide should not be taken by patients with active bacterial infections, active herpes-zoster viral infection, active or latent tuberculosis, or acute or chronic hepatitis B or C.

Hydroxychloroquine. Hydroxychloroquine (Plaquenil, generic) was originally used for preventing malaria and is now also used for mild, slowly progressive rheumatoid arthritis. It starts to improve symptoms within 1 - 2 months, but may take up to 6 months to achieve full benefit. It also does not appear to slow disease progression. Hydroxycholoroquine usually causes fewer side effects than other DMARDs. The most common side effects are nausea and diarrhea, which typically improve over time or when the drug is taken with food. Less common side effects include skin rash or bleaching or thinning of hair.

This drug used to be associated with eye and vision problems, but with current lower doses this side effect is rare. If vision problems occur, it is usually with people taking very high doses, those with kidney disease, or those over 60 years of age. Still, patients should have an eye exam (including retinal examination) within the first year of treatment. Patients with health risks (liver disease, retinal disease, over age 60) should have an annual eye exam. Patients should notify their doctors if they experience any sudden changes in vision.

Sulfasalazine. Sulfasalazine (Azulfidine, generic) works best when the disease is confined to the joints. Symptom relief occurs within 1 - 3 months.

Side effects are common, particularly stomach and intestinal distress, which usually occur early in the course of treatment. (However, serious gastrointestinal side effects, such as stomach ulcers, occur less frequently with sulfasalazine than with NSAIDs.) A coated-tablet form may help reduce side effects. Other side effects include skin rash and headache. Sulfasalazine increases sensitivity to sunlight. Be sure to wear sunscreen (SPF 15 or higher) while taking this drug. People with intestinal or urinary obstructions or who have allergies to sulfa drugs or salicylates should not take sulfasalazine.

Gold. Gold has been a time-honored DMARD for rheumatoid arthritis, although its use has decreased with the development of disease modifying and biologic drugs. Gold is usually administered in an injected form because the oral form, auranofin (Ridaura, generic), is much less effective. There are two injectable forms of gold: Gold sodium thiomalate (Myochrysine, generic) and aurothioglucose (Solganal, generic). It can take 3 - 6 months before injections have an effect on RA symptoms.

Gold injections cause mouth sores in about a third of patients. Skin side effects, including itching and rash, can be severe in some patients. The most serious side effects of gold injections, while rare, are kidney damage and decreased white blood cell count. Gold injections are usually not given to pregnant women. It is not definite that gold causes birth defects, but doctors generally recommend women use birth control while receiving this drug.

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Review Date: 02/16/2011
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org)