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Home » Drug Information » FDA Approved Drugs » 2008
Medical Areas: Musculoskeletal | Pediatrics/Neonatology | Rheumatology

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Orencia (abatacept)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company: Bristol-Myers Squibb
Approval Status: Approved April 2008
Treatment Area: Juvenile Idiopathic Arthritis

General Information

Orencia is a soluble fusion protein that consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to the modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1). Abatacept is produced by recombinant DNA technology in a mammalian cell expression system. The drug has activity as a selective costimulation modulator with inhibitory activity on T lymphocytes.

Orencia is specifically indicated for reducing signs and symptoms in pediatric patients 6 to 17 years of age with moderately to severely active polyarticular juvenile idiopathic arthritis. It may be used as monotherapy or concomitantly with methotrexate (MTX).

Orencia is supplied as a lyophilized powder for intravenous infusion in an individually packaged, single-use vial with a silicone-free disposable syringe. The recommended initial dose of the drug is based on individual body weight:

Less than 75 kg: 10 mg/kg calculated based on the patient’s body weight at each administration.

75 kg or more: Orencia should be administered following the adult dosing regimen, not to exceed a maximum dose of 1000 mg.

Orencia should be administered as a 30-minute intravenous infusion. Following the initial administration, Orencia should be given at 2 and 4 weeks after the first infusion and every 4 weeks thereafter.

Clinical Results

FDA Approval
FDA approval of Orencia for this indication was based on the results of a three-part study including an open-label extension. The study enrolled 190 pediatrics with moderately to severely active polyarticular JIA who had an inadequate response to one or more DMARDs, such as MTX or TNF antagonists.

In Period A, an open-label, lead-in phase, patients received 10 mg/kg (maximum 1000 mg per dose) intravenously on days 1, 15, 29, and monthly thereafter. Response was assessed utilizing the ACR Pediatric 30 definition of improvement,6 defined as =30% improvement in at least 3 of the 6 JIA core set variables and =30% worsening in not more than 1 of the 6 JIA core set variables. Patients demonstrating an ACR Pedi 30 response at the end of Period A were randomized into the double-blind phase, Period B, and received either Orencia or placebo for 6 months or until disease flare.

Period A
At the conclusion of Period A, pediatric ACR 30/50/70 responses were 65%, 50%, and 28%, respectively. Pediatric ACR 30 responses were similar in all subtypes of JIA studied.

Period B
During this double-blind randomized withdrawal phase, Orencia-treated patients experienced significantly fewer disease flares compared to placebo-treated patients (20% vs 53%); 95% CI of the difference (15%, 52%). The risk of disease flare among patients continuing on Orencia was less than one third than that for patients withdrawn from Orencia treatment (hazard ratio=0.31, 95% CI [0.16, 0.59]).

Among patients who received Orencia throughout the study (Period A, Period B, and the open-label extension Period C), the proportion of pediatric ACR 30/50/70 responders remained consistent for 1 year.

Side Effects

Adverse events associated with the use of Orencia in this population may include, but are not limited to, the following:

  • Upper respiratory tract infection
  • Nasopharyngitis
  • Headache
  • Nausea
  • Diarrhea
  • Cough
  • Pyrexia
  • Abdominal pain

Concurrent administration of a TNF antagonist with ORENCIA has been associated with an increased risk of serious infections and no significant additional efficacy over use of the TNF antagonists alone. Concurrent therapy with ORENCIA and TNF antagonists is not recommended.

Mechanism of Action

Abatacept, a selective costimulation modulator, inhibits T cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. This interaction provides a costimulatory signal necessary for full activation of T lymphocytes. Activated T lymphocytes are implicated in the pathogenesis of RA and are found in the synovium of patients with RA.

Literature References

Haines KA Juvenile idiopathic arthritis: therapies in the 21st century. Bulletin of the NYU hospital for joint diseases 2007;65(3):205-11

Passo M Emerging therapies in juvenile rheumatoid/idiopathic arthritis. Current problems in pediatric and adolescent health care 2006 Mar;36(3):97-103

Vital EM, Emery P Abatacept Drugs of today 2006 Feb;42(2):87-93

Additional Information

For additional information regarding Orencia or Juvenile Idiopathic Arthritis, please visit the Orencia web page.