The first agents in this category were inhibitors of TNF-α (anti–TNF-α agents). Currently, five of these drugs have been approved by the U.S. Food and Drug Administration:

• Adalimumab (fully human monoclonal antibody)

• Certolizumab (pegylated humanized Fab′ fragment of TNF monoclonal Ab)

• Etanercept (fusion protein: TNF receptor attached to the Fc region of human IgG)

• Golimumab (fully human monoclonal antibody)

• Infliximab (chimeric monoclonal antibody)

Anti–TNF-α drugs are usually the first biologic agent used in patients with rheumatoid arthritis. These agents are subcutaneous injections, except infliximab, which is an intravenous preparation. The side effects are similar among all and include injection or infusion reactions, infections, and, rarely, demyelinating diseases and malignancies. Patients need to be screened for latent infections, including tuberculosis, before treatment.

Anakinra, an IL-1 inhibitor, is available but has lost favor over time. It is injected subcutaneously daily. It has not shown as robust of a response as other biologic agents in treating rheumatoid arthritis.

Abatacept is a fusion protein of CTLA4-Ig and blocks T-cell co-stimulation. The drug is delivered intravenously once a month. Side effects have included infusion reactions and infections.

Rituximab depletes B lymphocytes as a monoclonal antibody against CD20. It is also given intravenously in two infusions separated by 2 weeks. Treatments may be repeated at 6-month intervals. Infusion reactions and infections remain the most significant risks.

Tocilizumab is an IL-6 receptor antagonist given intravenously every 4 weeks. Risks have included infusion reaction, infections, and elevated liver transaminase levels.

Combinations of DMARDs. Controversy exists on the proper use of combination DMARD therapy. Strategies have included the following:

• Sequential monotherapy

• Initial combination therapy

• Step-up combination therapy

• Step-down combination therapy

Nonbiologic DMARDs can be combined together. The combination of methotrexate and leflunomide carries the increased risks of hepatic and hematologic toxicity. In patients who have had an inadequate response to methotrexate, a biologic agent (most commonly an anti–TNF-α drug) is commonly added. Most agree that biologic DMARD agents should not be combined, owing to the increased infectious risks.

SURGICAL TREATMENT

The benefits of surgical approaches to rheumatoid arthritis are pain relief and restoration of function. Surgical options include synovectomy, arthroplasty, and arthrodesis (see Plate 5-12). Synovectomy of joint and/or tendons is available for almost all joints. Arthroplasty is a well-accepted treatment strategy for arthritis of the hands, shoulders, and especially the hips and knees. However, advances in elbow, wrist, and ankle joint arthroplasty are also being made. Arthrodesis, or joint fusion, can be helpful for intractable disease of the fingers, wrists, toes, or ankles. Although surgical options are typically postponed for medical therapies, one should not ignore the pain relief and functional benefits afforded the appropriate patient by these techniques. Technologic advancements in the field of orthopaedics will improve surgical outcomes and replacement longevity.