by Agent G

Created on: July 21, 2009

There are many agents available for the management of rheumatoid arthritis (RA). Three agents have been approved by the FDA relatively recently. The first, abatacept, is a selective costimulation modulator that inhibits T cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. It has been shown to be effective in slowing radiographic progression and reducing the signs and symptoms of active RA in patients with inadequate responses to methotrexate and/or anti-TNF therapy.

Infusion site reactions are seen in 8.8% of individuals in patients receiving abatacept (Orenciatm). (Kremer 2006) The most commonly observed adverse events are headache, nasopharyngitis, and dizziness. The most serious adverse event was infection; other adverse events included pneumonia (0.4-0.9% vs 0-0.05% on placebo), cellulitis, urinary tract infections, and diverticulitis.

The AIM trial demonstrated that abatacept in combination with disease modifying antirheumatic drugs (DMARDs) is well tolerated and improves physical function. (Kremer 2006) However, abatacept in combination with other biological agents is associated with an increase in the rate of serious adverse events; therefore, abatacept is not recommended for use in combination with biologic therapy. When to use abatacept, as well as what to do upon failure, and if it is more efficacious than B-cell depletion, remains largely subjective.

In 2006, rituximab (MabTheratm) became available for the treatment of progressive RA. Rituximab, an anti-CD20 chimeric monoclonal antibody, is used in combination with methotrexate and works by depleting B cells. It has demonstrated efficacy in reducing both clinical signs and symptoms of RA and radiographic progression.

The most common adverse event observed with rituximab is an infusion reaction (approximately 35%), but this reaction has been found to significantly lessen during a second infusion (10%). (Furst 2007) In the aforementioned trial, a slight upward trend in the rate of infection was observed (4.7-5.2% vs. 3.2-3.7% on placebo).(Cohen 2006) However, the rate of serious infection remained stable even with retreatment. (van Vollenhoven 2007) While infection remains a serious concern whenever a patient is treated with a biologic agent, a study of 1053 patients with moderate-to-severe RA who were B-cell depleted due to use of rituximab did not show development of opportunistic infections or significant adverse events, even when the patients

• 1
• 2
• Next Page >>