Orencia (Abatacept) and Enbrel (Etanercept) should not be used together in the treatment of RA, according to a study published in the August 25 Online First issue of the A_nnals of Rheumatic Diseases_. The goal of the research was to study the efficacy and safety of abatacept when taken together with etanercept in patients with active rheumatoid arthritis (RA). The trial consisted of a 1-year, randomized, placebo-controlled, double-blind (DB) phase, followed by an open-label, long-term extension (LTE).
A total of 121 Patients received etanercept (25 mg biweekly) and were randomized to receive either abatacept 2 mg/kg (n=85) or placebo (n=36). 80 completed the therapy and participated in the long-term extension. During the long-term extension, all patients received abatacept 10 mg/kg and etanercept because the effective dose of abatacept was established as 10 mg/kg in a separate trial.
During the double-blind phase of the study, the there was no significant difference in the percentage of patients achieving the primary endpoint (modified American College of Rheumatology [ACR] 0 response at 6 months) between the abatacept and placebo groups (48.2% versus 30.6%; p=0.072). There were also no notable changes in modified ACR responses observed at the one-year mark. During the long-term extension, after the change in dosage, the research found a similar modified ACR response. The researchers found that patients had significant improvements in quality of life with the combination of abatacept and etanercept versus placebo/etanercept in five of the eight Short Form-36 (SF-36) subscales at 1 year. The abatacept plus etanercept-treated patients were more likely to experience serious adverse events (SAEs) at 1 year than patients receiving placebo plus etanercept (16.5% vs 2.8%), with 3.5% vs 0% experiencing serious infections.
The study results showed that the combination of abatacept (dosed at 2 mg/kg during the DB phase and 10 mg/kg during the LTE) plus etanercept was associated with an increase in serious adverse events, including serious infections, with limited clinical effect. The researchers concluded that based on the limited efficacy of the findings and safety concerns, abatacept should not be used in combination with etanercept to treat RA.
The researchers noted that one Study limitation was the inability to draw firm efficacy conclusions because of the use of the 2 mg/kg dose of abatacept during the double-blind phase. Also, there were a relatively low number of patients who received abatacept 10 mg/kg in the long-term extension, and enrollment discontinued before reaching the planned number of patients per protocol. The low participant numbers reduced the statistical power of the study. It should also be noted that abatacept is manufactured by Bristol-Myers Squibb. This company designed, funded, and analyzed the study. The company also employs 3 of the study’s authors; and has relevant financial relationships with several other authors, some of who also have various relevant financial relationships with Wyeth; Amgen (the maker of etanercept); Centocor; Abbott; and/or Genentech.