"Second-line" or "slow-acting" drugs (Disease-modifying anti-rheumatic drugs or DMARDs)

While "first-line" medications (NSAIDs and corticosteroids) can relieve joint inflammation and pain, they do not necessarily prevent joint destruction or deformity. Rheumatoid arthritis requires medications other than NSAIDs and corticosteroids to stop progressive damage to cartilage, bone, and adjacent soft tissues. The medications needed for ideal management of the disease are also referred to as disease-modifying anti-rheumatic drugs or DMARDs. They come in a variety of forms and are listed below. These "second-line" or "slow-acting" medicines may take weeks to months to become effective. They are used for long periods of time, even years, at varying doses. If effective, DMARDs can promote remission, thereby retarding the progression of joint destruction and deformity. Sometimes a number of second-line medications are used together as combination therapy. As with the first-line medications, the doctor may need to use different second-line medications before treatment is optimal.

Recent research suggests that patients who respond to a DMARD with control of the rheumatoid disease may actually decrease the known risk (small but real) of lymphoma that exists from simply having rheumatoid arthritis. The DMARDs are reviewed next.

Hydroxychloroquine (Plaquenil) is related to quinine and is also used in the treatment of malaria. It is used over long periods for the treatment of rheumatoid arthritis. Possible side effects include upset stomach, skin rashes, muscle weakness, and vision changes. Even though vision changes are rare, patients taking Plaquenil should be monitored by an eye doctor (ophthalmologist).

Sulfasalazine (Azulfidine) is an oral medication traditionally used in the treatment of mild to moderately severe inflammatory bowel diseases, such as ulcerative colitis and Crohn's colitis. Azulfidine is used to treat rheumatoid arthritis in combination with antiinflammatory medications. Azulfidine is generally well tolerated. Common side effects include rash and upset stomach. Because Azulfidine is made up of sulfa and salicylate compounds, it should be avoided by patients with known sulfa allergies.

Methotrexate has gained popularity among doctors as an initial second-line drug because of both its effectiveness and relatively infrequent side effects. It also has an advantage in dose flexibility (dosages can be adjusted according to needs). Methotrexate is an immune-suppression drug. It can affect the bone marrow and the liver, even rarely causing cirrhosis. All patients taking methotrexate require regular blood-test monitoring of blood counts and liver function blood tests.

Gold salts have been used to treat rheumatoid arthritis throughout most of the past century. Gold thioglucose (Solganal) and gold thiomalate (Myochrysine) are given by injection, initially on a weekly basis for months to years. Oral gold, auranofin (Ridaura), was introduced in the 1980s. Side effects of gold (oral and injectable) include skin rash, mouth sores, kidney damage with leakage of protein in the urine, and bone marrow damage with anemia and low white-cell count. Patients receiving gold treatment are regularly monitored with blood and urine tests. Oral gold can cause diarrhea. These gold drugs have lost such favor that many companies no longer manufacture them.

D-penicillamine (Depen, Cuprimine) can be helpful in selected patients with progressive forms of rheumatoid arthritis. Side effects are similar to those of gold. They include fever, chills, mouth sores, a metallic taste in the mouth, skin rash, kidney and bone marrow damage, stomach upset, and easy bruising. Patients on this medication require routine blood and urine tests. D-penicillamine can rarely cause symptoms of other autoimmune diseases.

Immunosuppressive medicines are powerful medications that suppress the body's immune system. A number of immunosuppressive drugs are used to treat rheumatoid arthritis. They include methotrexate (Rheumatrex, Trexall) as described above, azathioprine (Imuran), cyclophosphamide (Cytoxan), chlorambucil (Leukeran), and cyclosporine (Sandimmune). Because of potentially serious side effects, immunosuppressive medicines (other than methotrexate) are generally reserved for patients with very aggressive disease or those with serious complications of rheumatoid inflammation, such as blood vessel inflammation (vasculitis). The exception is methotrexate, which is not frequently associated with serious side effects and can be carefully monitored with blood testing. Methotrexate has become a preferred second-line medication as a result.

Immunosuppressive medications can depress bone-marrow function and cause anemia, a low white-cell count, and low platelet counts. A low white count can increase the risk of infections, while a low platelet count can increase the risk of bleeding. Methotrexate rarely can lead to liver cirrhosis and allergic reactions in the lung. Cyclosporin can cause kidney damage and high blood pressure. Because of potentially serious side effects, immunosuppressive medications are used in low doses, usually in combination with antiinflammatory agents.