The Food & Drug Administration has approved abatacept (Orencia, Bristol-Myers Squibb) for treating rheumatoid arthritis (RA) in patients with inadequate response to other therapies. Orencia is first in a new class of agents that inhibits T-lymphocyte activation by binding to CD80 and CD86, blocking the interaction with CD28.

This interaction provides a co-stimulatory signal necessary for full activation of T-lymphocytes. Activated T-lymphocytes are found in the synovium of patients with RA.

RA is an autoimmune disorder of unknown etiology and with no known cure, characterized by inflammation of the synovium. It can lead to long-term joint damage, chronic pain, disability, and loss of function. Over two million people in the United States are afflicted with RA, 70% of whom are women. RA can affect anyone, however, including children.

Treatment goals focus on relieving pain, reducing inflammation, and stopping or slowing joint damage. Achieving these goals requires pharmacologic therapies, often consisting of disease-modifying antirheumatic drugs (DMARDs) such as methotrexate or sulfasalazine; nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin or ibuprofen; glucocorticoid joint injection; and tumor necrosis factor (TNF) antagonists such as etanercept (Enbrel, Immunex/Amgen/Wyeth), adalimumab (Humira, Abbott), infliximab (Remicade, Centocor), and/or a combination of methotrexate and one of these agents.

The American College of Rheumatology (ACR) guidelines suggest that the majority of newly diagnosed patients should be started on a DMARD within three months of diagnosis. Physicians should consider changing or adding another DMARD in patients with inadequate response after three months of therapy. However, some patients have resistant disease despite multiple trials of DMARDs, alone or in combination, indicating a need for more therapies for RA.

Abatacept is indicated for reducing signs and symptoms, inducing major clinical response, slowing the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA who have shown inadequate response to one or more DMARDs or TNF antago-nists. Abatacept may be used as monotherapy or used concomitantly with DMARDs other than TNF antagonists.

"Orencia offers another option to patients who have failed methotrexate or TNF therapy," said Mark Genovese, M.D., associate professor of medicine at Stanford University School of Medicine, Palo Alto, Calif.

The safety and efficacy of abatacept have been studied in over 2,600 patients with active RA who have been diagnosed according to the ACR criteria. The phase III clinical trial program included three double-blind, randomized, placebo-controlled studies: the AIM trial compared abatacept in combination with methotrexate against methotrexate alone; ATTAIN compared abatacept in combination with nonbiologic DMARDs against nonbiologic DMARDs alone in patients with inadequate response to TNF antagonists etanercept and infliximab; and ASSURE studied the safety of abatacept compared with placebo when used in combination with biologic and nonbiologic DMARDs. Abatacept is the first approved agent to demonstrate efficacy and safety in patients with an inadequate response to TNF antagonists, as well as those with an inadequate response to MTX.

Abatacept is expected to be available for initial commercial use by the end of this month.

THE AUTHOR is a writer based in New Jersey.