Orencia: First T-cell Co-stimulation Modulator for Rheumatoid Arthritis
Orencia (generic: abatacept) is the first T-cell co-stimulation modulator approved for the treatment of rheumatoid arthritis (RA). Orencia, a fully human soluble fusion protein, works by selectively modulating a co-stimulatory signal which is required for full T-cell activation.
According to arthritis-research.com, "Activated T cells play a central role in the inflammatory cascade leading to the joint inflammation and destruction characteristic of rheumatoid arthritis. The cytokines secreted by activated T cells are thought to both initiate and propagate the immunologically driven inflammation associated with RA."
Orencia is a 30-minute intravenous infusion. The fixed dose is based on weight, 10mg/kg, at day 0, 2 weeks, 4 weeks, and continuing every 4 weeks.
Indications for Orencia
According to the drugmaker Bristol-Myers Squibb, Orencia is indicated for:
- reducing the signs and symptoms of rheumatoid arthritis
- inducing major clinical response (*defined as maintaining an ACR70 score for 6 months)
- slowing the progression of structural damage
- improving physical function to adult patients with moderate to severely active rheumatoid arthritis who have had an inadequate response to DMARDs (e.g., methotrexate or TNF blockers)
*ACR20, ACR50 and ACR70 indicate a 20, 50 or 70 percent improvement in the number of swollen and tender joints, as well as a 20, 50 or 70 percent improvement compared with baseline in three of five disease-activity measures.
Positive Clinical Trial Results for Orencia
In clinical trials, Orencia significantly reduced the signs and symptoms of rheumatoid arthritis among patients who had an inadequate response to DMARDS or anti-TNF therapy when compared to placebo. More than 2,600 patients were studied in an extensive clinical trial program. The Phase III clinical trial program included three double-blind, randomized, placebo-controlled studies:
- AIM (Abatacept in Inadequate responders to Methotrexate) - compared Orencia in combination with methotrexate to methotrexate alone
- ATTAIN (Abatacept Trial in Treatment of Anti-TNF Inadequate responders) - compared Orencia in combination with non-biologic DMARDs to non-biologic DMARDs alone in patients inadequate response to TNF blockers Enbrel (etanercept) and Remicade (infliximab)
- ASSURE (Abatacept Study of Safety in Use with other RA therapies) - studied the safety of Orencia compared to placebo when used in combination with biologic and non-biologic DMARDs
AIM and ASSURE were presented at the 2005 annual European League Against Rheumatism (EULAR) meeting. Top-line results of AIM were previously presented at the 2004 American College of Rheumatology (ACR) meeting. Results from were presented at the 2005 American College of Rheumatology meeting.
Orencia May Be Taken Alone or in Combination With Non-biologic DMARDs
Orencia should not be used concurrently with TNF blockers (Enbrel, Remicade, and Humira) and is not recommended for use with Anakinra. In clinical trials patients receiving Orencia and a TNF blocker concurrently had more infections, including serious infections, compared to patients taking TNF blockers alone.
Warnings exist for use of Orencia in patients with a history of infection or a predisposition for infection. Warnings also exist for patients testing positive for tuberculosis as well as patients with chronic obstructive pulmonary disease (COPD).
The most serious adverse reactions in clinical trials for Orencia were:
- serious infections (3% Orencia vs. 1.9% placebo)
- malignancies (1.3% Orencia vs. 1.1% placebo)
The most frequent adverse events occurring in greater than or equal to 10 percent of patients treated with Orencia included:
- upper respiratory tract infection
Infusion reactions were reported in 9% of patients receiving Orencia versus 6% in patients treated with placebo.
More About Orencia
Of about 2 million people who have rheumatoid arthritis, analysts estimate that 250,000 are on anti-TNF drug therapy. 15 to 25% of those patients on anti-TNF drug therapy have an inadequate response.
For more information about Orencia (abatacept), patients and healthcare providers can call 1-800-ORENCIA (673-6242) or go to Orencia.com
Long-Term Phase III Data On Investigational Biologic Orencia (Abatacept) Presented During Late-Breaking Session Of American College Of Rheumatology (ACR) Meeting, Bristol-Myers Squibb Press Release. 11/16/2005.
New Two-year ORENCIA (abatacept) AIM Data Presented at Annual EULAR Congress, Bristol-Myers Squibb Press Release. 06/23/2006.