Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial.
BACKGROUND
The selective co-stimulation modulator abatacept demonstrated efficacy for treating rheumatoid arthritis in early clinical studies.


OBJECTIVE
To evaluate the effects of abatacept in patients with persistent, active rheumatoid arthritis despite methotrexate treatment.


METHODS
One-year, multicenter, randomized, double-blind, placebo-controlled trial (November 2002 to October 2004).


METHODS
116 centers worldwide.


METHODS
652 patients with active rheumatoid arthritis despite methotrexate treatment.


METHODS
Once-monthly infusion of a fixed dose of abatacept, approximately 10 mg/kg of body weight, or placebo.


METHODS
Co-primary end points were a 20% improvement in American College of Rheumatology (ACR) response criteria (ACR 20) at 6 months, clinically meaningful improvements in physical function, and change from baseline in joint erosion score at 1 year.


RESULTS
Four hundred thirty-three and 219 patients were randomly assigned to abatacept or placebo, respectively, and 385 (89%) and 162 (74%), respectively, completed 1 year of treatment. In a modified intention-to-treat analysis, 6-month ACR 20, ACR 50, and ACR 70 responses were 67.9% for abatacept versus 39.7% for placebo (difference, 28.2 percentage points [95% CI, 19.8 to 36.7 percentage points]), 39.9% for abatacept versus 16.8% for placebo (difference, 23.0 percentage points [CI, 15.0 to 31.1 percentage points]), and 19.8% for abatacept versus 6.5% for placebo (difference, 13.3 percentage points [CI, 7.0 to 19.5 percentage points]), respectively. At 1 year, the responses increased to 73.1% for abatacept versus 39.7% for placebo (difference, 33.4 percentage points [CI, 25.1 to 41.7 percentage points]), 48.3% for abatacept versus 18.2% for placebo (difference, 30.1 percentage points [CI, 21.8 to 38.5 percentage points]), and 28.8% for abatacept versus 6.1% for placebo (difference, 22.7 percentage points [CI, 15.6 to 29.8 percentage points]), respectively (P < 0.001 for all). Physical function significantly improved in 63.7% versus 39.3% of patients (P < 0.001). At 1 year, abatacept statistically significantly slowed the progression of structural joint damage compared with placebo. Abatacept-treated patients had a similar incidence of adverse events (87.3% vs. 84.0%; difference, 3.3 percentage points [CI, -2.5 to 9.1 percentage points]) and a higher incidence of prespecified serious infections (2.5% vs. 0.9%; difference, 1.6 percentage points [CI, -0.3 to 3.6 percentage points]) and infusion reactions (acute, 8.8% vs. 4.1%; difference, 4.7 percentage points [CI, 0.9 to 8.4 percentage points]; peri-infusional, 24.5% vs. 16.9%; difference, 7.6 percentage points [CI, 1.2 to 14.0 percentage points]) compared with placebo recipients.


CONCLUSIONS
The study involved only 1 group of patients over 1 year.


CONCLUSIONS
Abatacept statistically significantly reduced disease activity in patients with rheumatoid arthritis and an inadequate response to methotrexate. Longer treatment in different patient populations is needed to establish its appropriate role in rheumatoid arthritis.
Kremer
Joel M
JM
Center for Rheumatology, Albany, New York, USA. jkremer@joint-docs.com
Genant
Harry K
HK
Moreland
Larry W
LW
Russell
Anthony S
AS
Emery
Paul
P
Abud-Mendoza
Carlos
C
Szechinski
Jacek
J
Li
Tracy
T
Ge
Zhiyu
Z
Becker
Jean-Claude
JC
Westhovens
Rene
R
D000069594:Abatacept; D000328:Adult; D000368:Aged; D000917:Antibody Formation; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004311:Double-Blind Method; D004351:Drug Resistance; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D007239:Infections / Q000209:etiology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011788:Quality of Life; D011859:Radiography; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D018796:Immunoconjugates; D000069594:Abatacept; D008727:Methotrexate