Selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving etanercept: a randomised clinical trial.
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.


CONCLUSIONS
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.
Weinblatt
Michael
M
Rheumatology and Immunology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. mweinblatt@partners.org
Schiff
Michael
M
Goldman
Allan
A
Kremer
Joel
J
Luggen
Michael
M
Li
Tracy
T
Chen
Dalei
D
Becker
Jean-Claude
JC
D000069594:Abatacept; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D002177:Candidiasis / Q000150:complications; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005260:Female; D006561:Herpes Simplex / Q000150:complications; D006562:Herpes Zoster / Q000150:complications; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007165:Immunosuppression Therapy; D007596:Joints / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D018796:Immunoconjugates; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000069594:Abatacept; D000068800:Etanercept