Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept: twelve-month results of a phase iib, double-blind, randomized, placebo-controlled trial.
OBJECTIVE
To determine the clinical efficacy, safety, and immunogenicity of abatacept (CTLA-4Ig), a selective costimulation modulator, in patients with rheumatoid arthritis (RA) that has remained active despite methotrexate (MTX) therapy.


METHODS
This was a 12-month, multicenter, randomized, double-blind, placebo-controlled study. A total of 339 patients with active RA despite MTX therapy were randomly assigned to receive 10 mg/kg abatacept (n = 115), 2 mg/kg abatacept (n = 105), or placebo (n = 119). This report focuses on the results observed at month 12 of a phase IIb trial.


RESULTS
A significantly greater percentage of patients treated with 10 mg/kg abatacept met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at 1 year compared with patients who received placebo (62.6% versus 36.1%; P < 0.001). Greater percentages of patients treated with 10 mg/kg abatacept also achieved ACR50 responses (41.7% versus 20.2%; P < 0.001) and ACR70 responses (20.9% versus 7.6%; P = 0.003) compared with patients who received placebo. For patients treated with 10 mg/kg abatacept, there were also statistically significant and clinically important improvements in modified Health Assessment Questionnaire scores compared with patients who received placebo (49.6% versus 27.7%; P < 0.001). Abatacept at a dosage of 10 mg/kg elicited an increase in rates of remission (Disease Activity Score in 28 joints of <2.6) compared with placebo at 1 year (34.8% versus 10.1%; P < 0.001). The incidence of adverse events was comparable between the groups, and no significant formation of neutralizing antibodies was noted.


CONCLUSIONS
Abatacept was associated with significant reductions in disease activity and improvements in physical function that were maintained over the course of 12 months in patients with RA that had remained active despite MTX treatment. Abatacept was found to be well tolerated and safe over the course of 1 year. Abatacept in combination with MTX has the potential to play an important role in future RA therapy.
Kremer
Joel M
JM
Center for Rheumatology, Albany, NY 12206, USA. jkremer@joint-docs.com
Dougados
Maxime
M
Emery
Paul
P
Durez
Patrick
P
Sibilia
Jean
J
Shergy
William
W
Steinfeld
Serge
S
Tindall
Elizabeth
E
Becker
Jean-Claude
JC
Li
Tracy
T
Nuamah
Isaac F
IF
Aranda
Richard
R
Moreland
Larry W
LW
D000069594:Abatacept; D000917:Antibody Formation; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006304:Health Status; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D012074:Remission Induction; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D018796:Immunoconjugates; D000069594:Abatacept