Selective costimulation modulation using abatacept in patients with active
rheumatoid arthritis while receiving etanercept: a randomised clinical trial.
Author(s): Weinblatt M, Schiff M, Goldman A, Kremer J, Luggen M, Li T, Chen D, Becker JC.
Affiliation(s): Rheumatology and Immunology, Brigham and Women's Hospital, 75 Francis Street,
Boston, MA 02115, USA. mweinblatt@partners.org
Publication date & source: 2007, Ann Rheum Dis. , 66(2):228-34
OBJECTIVE: To investigate the efficacy and safety of abatacept in combination
with etanercept in patients with active rheumatoid arthritis during a 1-year,
randomised, placebo-controlled, double-blind phase, followed by an open-label,
long-term extension (LTE).
METHODS: Patients continued etanercept (25 mg twice weekly) and were randomised
to receive abatacept 2 mg/kg (n = 85) or placebo (n = 36). As the effective dose
of abatacept was established as 10 mg/kg in a separate trial, all patients
received abatacept 10 mg/kg and etanercept during the LTE.
RESULTS: A total of 121 patients were randomised; 80 completed double-blind
treatment and entered the LTE. During double-blind treatment, the difference in
the percentage of patients achieving the primary end point (modified American
College of Rheumatology (ACR) 20 response at 6 months) was not significant
between groups (48.2% v 30.6%; p = 0.072). At 1 year, no notable changes in
modified ACR responses were observed. Subsequent to the dosing change, similar
modified ACR responses were seen during the LTE. Significant improvements in
quality of life were observed with abatacept and etanercept versus placebo and
etanercept in five of the eight short-form 36 subscales at 1 year. More abatacept
and etanercept-treated patients experienced serious adverse events (SAEs) at 1
year than patients receiving placebo and etanercept (16.5% v 2.8%), with 3.5% v
0% experiencing serious infections.
CONCLUSION: The combination of abatacept (at a dose of 2 mg/kg during the
double-blind phase and 10 mg/kg during the LTE) and etanercept was associated
with an increase in SAEs, including serious infections, with limited clinical
effect. On the basis of the limited efficacy findings and safety concerns,
abatacept in combination with etanercept should not be used for rheumatoid
arthritis treatment.
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