Nonsteroidal Anti-inflammatory Drugs (NSAIDs). NSAIDs interfere with the production of prostaglandins and thus are effective in the reduction of inflammation and, therefore, pain. Many patients will require these agents along with DMARDs for pain management, but NSAIDs should be considered adjunctive and not be used alone for rheumatoid arthritis. There are no data to support NSAIDs as DMARDs. They can also be helpful as a bridge therapy while DMARDs are being initiated. Gastrointestinal adverse effects, including peptic ulcer disease and gastrointestinal bleeding, are the most common reason for discontinuation of these agents. These drugs will be contraindicated or receive limited use in those patients with backgrounds of gastrointestinal bleeding and chronic kidney and liver disease. Cyclooxygenase (COX)-selective NSAIDs (celecoxib) have the advantage of decreased gastrointestinal toxicity, but there remains concern about increased cardiovascular risk in this class compared with the nonselective NSAIDs.

Corticosteroids. As with NSAIDs, systemic corticosteroids can be a beneficial adjunct or bridge therapy (when starting a DMARD) in patients with rheumatoid arthritis. These drugs are very effective in reducing inflammation and, likewise, the signs and symptoms of the disease. Their side effects, including weight gain, cataracts, hypertension, diabetes, infection, and osteoporosis, typically limit their more long-term use; however, some patients may require longer-term use with lower dosages to retain joint function. Intra-articular corticosteroids can be useful when one or two joints remain inflamed in the presence of DMARD therapy or during a flare of the arthritis.

Nonbiologic Disease Modifying Anti-Rheumatic Drugs (DMARDs). DMARD therapy is the cornerstone of the treatment of rheumatoid arthritis. These drugs inhibit inflammatory responses, suppress synovitis, and, in studies, have been shown to improve the signs and symptoms of rheumatoid arthritis and to slow the natural progression of the joint damage. Unless contraindicated or refused, all patients should be started on a DMARD at diagnosis. Patients may not respond to DMARD therapy for up to 3 months after a therapeutic dose is achieved. The evaluation of efficacy requires frequent monitoring of disease activity.

The most common DMARDs are:

• Methotrexate

• Leflunomide

• Sulfasalazine

• Hydroxychloroquine

Methotrexate has become the most commonly used member of this group. It is given either orally or subcutaneously at dosages of 7.5 to 25 mg a week. Common side effects include rash, oral ulcers, nausea, and hair loss. More serious side effects including significant cytopenias, cirrhosis, and pulmonary fibrosis are quite rare with these low dosages and close monitoring. Methotrexate is contraindicated in patients with chronic kidney and liver disease, with moderate alcohol use, in pregnancy, and in women and men actively attempting conception.

Leflunomide is given orally at 10 to 20 mg/day. Common side effects include rash, diarrhea, and alopecia. Elevated liver transaminase levels and cytopenias can be observed. This drug is also contraindicated in pregnancy and in women and men actively attempting conception.

Sulfasalazine is given orally at divided dosages from 1000 to 3000 mg a day, typically starting at lower dosages. This drug is rarely used alone in a patient with a poor prognosis or high disease activity. Adverse effects include abdominal pain, diarrhea, nausea, rash, and, rarely, cytopenias and renal or hepatic dysfunction.

Hydroxychloroquine is likewise recommended for patients with better prognosis and less severe disease. Typical dosages are in the range of 200 to 400 mg/day. It is the best tolerated of all of the DMARDs and rarely will cause rash or gastrointestinal upset. The well-described retinal toxicity is extremely rare when used at dosages of less than 6 mg/kg/day. Routine eye examinations (tangent screen) are required and can detect early toxicity, which is reversible on discontinuation.