New disease modifying agents in adult rheumatoid arthritis.

In recent years, new disease modifying agents including leflunomide and tumour necrosis factor (TNF) antagonists have been used to treat patients with rheumatoid arthritis (RA). Leflunomide prevents proliferation of activated lymphocytes by inhibiting dihydroorotate dehydrogenase, a critical step in de novo pyrimidine synthesis. Leflunomide has been shown to be as effective as sulfasalazine and methotrexate (MTX) in placebo-controlled trials. It also improves physical function, quality of life measures and retards radiographic progression. TNF antagonists include infliximab and etanercept. Infliximab is a chimeric TNF monoclonal antibody. Repeated infusions of low dose infliximab (1 mg/kg) are ineffective if given alone. Addition of MTX to infliximab has been shown to prolong the duration of clinical response. Etanercept is a human TNF receptor p75 Fc fusion protein. In active RA patients with suboptimal response to MTX, additional clinical benefit was obtained by the addition of infliximab or etanercept to MTX. The main side effect of etanercept is injection site reaction. However, the long-term effect of TNF antagonists in the development of infection, malignancy and autoimmune disease remains unknown.