Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 62 of 137 for:    "Connective Tissue Disease" | "Abatacept"

Abatacept and Infliximab in Combination With Methotrexate in Subjects With Rheumatoid Arthritis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00095147
Recruitment Status : Completed
First Posted : November 2, 2004
Results First Posted : January 21, 2011
Last Update Posted : March 24, 2015
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: Abatacept (ABA) + Methotrexate (MTX), double-blind (DB)
Drug: Infliximab (INF) + MTX, DB
Drug: Placebo (PLA) + MTX, DB
Drug: PLA + MTX switched to ABA+ MTX, DB
Drug: ABA, open-label (OL)
Enrollment 431
Recruitment Details  
Pre-assignment Details 748 participants enrolled in this study; 317 participants were not randomized or treated. 384 participants completed the double-blind period; 12 participants did not enter the open-label period.
Arm/Group Title Abatacept (ABA) + Methotrexate (MTX) [Double-blind (DB)] Infliximab (INF) + MTX [DB] Placebo (PLA) + MTX [DB] PLA Switched to ABA + MTX [DB] ABA + MTX [Open-label (OL)]
Hide Arm/Group Description Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly). Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly) Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly) Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly). All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
Period Title: Double-blind Period 1 (Days 1-197)
Started 156 165 110 0 0
Completed 147 152 107 0 0
Not Completed 9 13 3 0 0
Reason Not Completed
Death             1             0             0             0             0
Adverse Event             2             8             1             0             0
Lack of Efficacy             2             2             1             0             0
Lost to Follow-up             2             2             0             0             0
Withdrawal of consent             1             0             1             0             0
Pregnancy             1             1             0             0             0
Period Title: Double-blind Period 2 (Days 198-365)
Started 147 152 0 107 0
Completed 139 141 0 104 0
Not Completed 8 11 0 3 0
Reason Not Completed
Death             0             1             0             1             0
Adverse Event             2             4             0             0             0
Lack of Efficacy             2             4             0             1             0
Withdrawal of consent             3             2             0             0             0
Participant relocation             1             0             0             1             0
Period Title: Long-term Extension Period
Started 0 0 0 0 372
Completed 0 0 0 0 327
Not Completed 0 0 0 0 45
Reason Not Completed
Death             0             0             0             0             3
Adverse Event             0             0             0             0             11
Lack of Efficacy             0             0             0             0             9
Lost to Follow-up             0             0             0             0             6
Withdrawal of consent             0             0             0             0             12
Pregnancy             0             0             0             0             1
No longer meets study criteria             0             0             0             0             1
Participant chose to use Revellex             0             0             0             0             1
Leaving country             0             0             0             0             1
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB] Total
Hide Arm/Group Description Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly). Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly) Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly) Total of all reporting groups
Overall Number of Baseline Participants 156 165 110 431
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 156 participants 165 participants 110 participants 431 participants
49.0  (12.5) 49.1  (12.0) 49.4  (11.5) 49.1  (12.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 156 participants 165 participants 110 participants 431 participants
Female
130
  83.3%
136
  82.4%
96
  87.3%
362
  84.0%
Male
26
  16.7%
29
  17.6%
14
  12.7%
69
  16.0%
Baseline Disease Activity Score (DAS) 28 (Erythrocyte Sedimentation Rate [ESR])   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 156 participants 165 participants 110 participants 431 participants
6.9  (1.0) 6.8  (0.9) 6.8  (1.0) 6.8  (1.0)
[1]
Measure Description: The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or C-reactive protein (CRP), and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response= decrease in DAS28 score of >1.2 from baseline.
1.Primary Outcome
Title DB; Adjusted Mean Change From Baseline to Day 197 in Disease Activity Score (DAS) 28 Score (Erythrocyte Sedimentation Rate [ESR]) For ABA Versus PLA (Last Observation Carried Forward [LOCF] Analysis)
Hide Description The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or C-reactive protein (CRP), and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.
Time Frame Baseline (Day 1), 6 months (Day 197)
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.
Arm/Group Title ABA + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 150 102
Mean (Standard Error)
Unit of Measure: units on a scale
-2.53  (0.12) -1.48  (0.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX [DB], PLA + MTX [DB]
Comments The primary analysis was the comparison of abatacept versus placebo for changes from baseline to 6 months (Day 197) in the DAS28. This comparison was done using an analysis of covariance (ANCOVA) model with treatment group as the effect and baseline value as the covariate. A 95% confidence interval was computed for the treatment difference within the framework of the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean change from baseline
Estimated Value -1.04
Confidence Interval (2-Sided) 95%
-1.42 to -0.67
Estimation Comments [Not Specified]
2.Primary Outcome
Title OL; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, and AEs Leading to Discontinuation
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.
Arm/Group Title ABA + MTX [OL]
Hide Arm/Group Description:
All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
Overall Number of Participants Analyzed 372
Measure Type: Number
Unit of Measure: participants
Deaths 3
SAEs 90
Related SAEs 12
SAEs Leading to Discontinuation 5
AEs 349
Related AEs 165
AEs Leading to discontinuation 10
3.Primary Outcome
Title OL; Number of Participants With AEs of Special Interest
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
Time Frame From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.
Arm/Group Title ABA + MTX [OL]
Hide Arm/Group Description:
All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
Overall Number of Participants Analyzed 372
Measure Type: Number
Unit of Measure: participants
Infections 277
Malignant neoplasms 3
Benign and unspecified neoplasms 18
Prespecified autoimmune symptoms and disorders 13
Pre-specified peri-infusional AEs 50
Pre-specified acute infusional AEs 28
4.Primary Outcome
Title OL; Number of Participants With Select Hematologic Laboratory Abnormalities
Hide Description High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Erythrocytes: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; lymphocytes: <0.750 x 10^3 c/uL/ >7.50 x 10^3 c/uL; monocytes: >2000 mm3; eosinophils: >0.750 x 10^3 c/uL;
Time Frame From Day 366 through end of OL (range from 1.9 months to 42.3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.
Arm/Group Title ABA + MTX [OL]
Hide Arm/Group Description:
All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
Overall Number of Participants Analyzed 372
Measure Type: Number
Unit of Measure: participants
Low HGB (>3g/dL decrease from BL), n=372 9
Low hematocrit (< 0.75 x BL), n=372 7
Low erythrocytes (<0.75 x BL), n=372 6
Low PLT (<0.67 x LLN), n=370 2
High leukocytes (>1.25 x ULN), n=372 29
Low neutrophils + bands (<1.0 x 10^3 c/uL), n=372 1
Low lymphocytes (<0.75 x 10^3 c/uL), n=372 12
High monocytes (>2000/mm^3), n=372 3
High eosinophils (>0.750 x 10^3 c/uL), n=372 15
5.Primary Outcome
Title OL; Number of Participants With Select Blood Chemistry Laboratory Abnormalities
Hide Description Low=lower than LLN, High=greater than ULN. LLN/ULN= Alkaline phosphatase (ALP): >2 x ULN; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL
Time Frame From Day 366 through end of OL (range from 1.9 months to 42.3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.
Arm/Group Title ABA + MTX [OL]
Hide Arm/Group Description:
All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
Overall Number of Participants Analyzed 371
Measure Type: Number
Unit of Measure: participants
High ALP (>2 x ULN) 1
High AST (>3 x ULN) 4
High ALT (>3 x ULN) 11
High GGT (>2 x ULN) 16
High total bilirubin (>2 x ULN) 1
High BUN (>2 x BL) 17
High creatinine (>1.5 increase from BL) 44
6.Primary Outcome
Title OL; Mean Change From Baseline to Day 365 in Hemoglobin, Total Protein, and Albumin
Hide Description Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN
Time Frame Baseline (Day 1), Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 131 136 104
Mean (Standard Error)
Unit of Measure: g/dL
HGB (n=131, n=135, n=103) 0.53  (0.09) 0.24  (0.09) 0.43  (0.09)
Total protein (n=131, n=136, n=104) -0.09  (0.04) 0.11  (0.04) -0.12  (0.04)
Albumin (n=131, n=136, n=104) 0.12  (0.03) 0.00  (0.03) 0.05  (0.03)
7.Primary Outcome
Title OL; Mean Change From Baseline to Day 365 in Platelets
Hide Description Platelets (PLT): <0.67 x LLN, >1.5 x ULN
Time Frame Baseline (Day 1), Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 129 129 102
Mean (Standard Error)
Unit of Measure: 10^9 c/L
-42.4  (5.20) -35.5  (6.93) -28.4  (6.75)
8.Primary Outcome
Title OL; Mean Change From Baseline to Day 365 in Hematocrit
Hide Description Hematocrit: <0.75 x BL
Time Frame Baseline (Day 1), Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 129 134 102
Mean (Standard Error)
Unit of Measure: percentage red blood cells
1.44  (0.29) 0.51  (0.27) 1.03  (0.27)
9.Primary Outcome
Title OL; Mean Change From Baseline to Day 365 in White Blood Cells
Hide Description Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.
Time Frame Baseline (Day 1), Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 131 134 104
Mean (Standard Error)
Unit of Measure: 10^3 c/uL
Leukocytes (n=131, n=134, n=103) -0.95  (0.23) -0.90  (0.21) -0.84  (0.23)
Neutrophils + bands (n=130, n=130, n=104) -0.91  (0.20) -1.14  (0.20) -1.05  (0.22)
Basophils (n=130, n=130, n=101) -0.01  (0.00) 0.00  (0.00) 0.00  (0.00)
Monocytes (n=130, n=130, n=101) -0.01  (0.02) -0.01  (0.02) 0.02  (0.02)
Eosinophils (n=130, n=130, n=101) -0.04  (0.01) -0.02  (0.02) -0.03  (0.01)
Lymphocytes (n=130, n=130, n=101) 0.03  (0.07) 0.24  (0.06) 0.22  (0.08)
10.Primary Outcome
Title OL; Mean Change From Baseline to Day 365 in Erythrocytes
Hide Description Erythrocytes: <0.75 x BL
Time Frame Baseline (Day 1), Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 131 135 103
Mean (Standard Error)
Unit of Measure: 10^6 c/uL
0.09  (0.03) 0.00  (0.03) 0.006  (0.03)
11.Primary Outcome
Title OL; Mean Change From Baseline to Day 365 in Electrolytes
Hide Description Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN
Time Frame Baseline (Day 1), Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 131 136 104
Mean (Standard Error)
Unit of Measure: mEq/L
Na (n=131, n=136, n=104) -1.62  (0.29) -1.57  (0.33) -1.09  (0.38)
K (n=131, n=135, n=104) -0.03  (0.04) -0.07  (0.04) -0.03  (0.05)
Cl (n=131, n=136, n=104) -1.40  (0.28) -1.18  (0.31) -1.06  (0.33)
12.Primary Outcome
Title OL; Mean Change From Baseline to Day 365 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Hide Description Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;
Time Frame Baseline (Day 1), Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 131 136 104
Mean (Standard Error)
Unit of Measure: mg/dL
Creatinine (n=131, n=136, n=104) 0.03  (0.02) 0.02  (0.01) 0.01  (0.02)
BUN (n=131, n=136, n=104) -0.31  (0.41) -0.52  (0.40) 0.10  (0.53)
Ca (n=131, n=136, n=104) 0.14  (0.04) 0.08  (0.03) 0.14  (0.04)
P (n=131, n=136, n=104) 0.03  (0.05) -0.01  (0.05) 0.05  (0.05)
Uric Acid (n=131, n=136, n=104) 0.09  (0.08) 0.08  (0.10) 0.04  (0.12)
Total bilirubin (n=131, n=134, n=104) 0.06  (0.01) 0.04  (0.02) 0.03  (0.02)
Serum glucose (n=131, n=136, n=104) 5.66  (2.41) 2.49  (3.15) 3.03  (2.16)
13.Primary Outcome
Title OL; Mean Change From Baseline to Day 365 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
Hide Description alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN
Time Frame Baseline (Day 1), Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 131 136 104
Mean (Standard Error)
Unit of Measure: U/L
ALT (n=131, n=135, n=104) 3.51  (1.33) 2.19  (2.31) -0.04  (1.68)
AST (n=131, n=135, n=104) 0.54  (1.04) -0.11  (1.51) -2.23  (1.41)
GGT (n=131, n=135, n=104) 2.53  (2.81) -0.61  (1.76) -2.32  (2.73)
ALP (n=131, n=136, n=104) -0.53  (2.16) -7.78  (2.24) -4.34  (2.48)
14.Primary Outcome
Title OL; Mean Change From Baseline to Day 729 in Hemoglobin, Total Protein, and Albumin
Hide Description Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN
Time Frame Baseline (Day 1), Day 729
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 124 127 102
Mean (Standard Error)
Unit of Measure: g/dL
HGB (n=124, n=125, n=102) 0.66  (0.10) 0.48  (0.10) 0.40  (0.13)
Total protein (n=124, n=127, n=102) -0.33  (0.05) -0.25  (0.04) -0.29  (0.05)
Albumin (n=124, n=127, n=102) 0.13  (0.03) 0.10  (0.03) 0.06  (0.03)
15.Primary Outcome
Title OL; Mean Change From Baseline to Day 729 in Platelets
Hide Description Platelets (PLT): <0.67 x LLN, >1.5 x ULN
Time Frame Baseline (Day 1), Day 729
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 124 122 100
Mean (Standard Error)
Unit of Measure: 10^9 c/L
-63.9  (6.04) -5832  (7.66) -47.7  (8.16)
16.Primary Outcome
Title OL; Mean Change From Baseline to Day 729 in Hematocrit
Hide Description Hematocrit: <0.75 x BL
Time Frame Baseline (Day 1), Day 729
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 124 124 102
Mean (Standard Error)
Unit of Measure: percentage of red blood cells
1.72  (0.29) 1.23  (0.29) 0.99  (0.38)
17.Primary Outcome
Title OL; Mean Change From Baseline to Day 729 in White Blood Cells
Hide Description Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.
Time Frame Baseline (Day 1), Day 729
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 124 125 102
Mean (Standard Error)
Unit of Measure: 10^3 c/uL
Leukocytes (n=124, n=125, n=102) -1.57  (0.23) -1.23  (0.26) -1.28  (0.23)
Neutrophils + bands (n=123, n=123, n=101) -1.62  (0.21) -1.35  (0.23) -1.33  (0.22)
Basophils (n=123, n=123, n=101) -0.01  (0.00) 0.00  (0.00) -0.01  (0.00)
Monocytes (n=123, n=123, n=101) -0.05  (0.02) -0.02  (0.04) -0.03  (0.02)
Eosinophils (n=123, n=123, n=101) -0.01  (0.01) -0.03  (0.02) -0.05  (0.02)
Lymphocytes (n=123, n=123, n=101) 0.13  (0.06) 0.18  (0.06) 0.08  (0.06)
18.Primary Outcome
Title OL; Mean Change From Baseline to Day 729 in Erythrocytes
Hide Description Erythrocytes: <0.75 x BL
Time Frame Baseline (Day 1), Day 729
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 124 125 102
Mean (Standard Error)
Unit of Measure: 10^6 c/uL
0.07  (0.03) 0.04  (0.03) 0.02  (0.04)
19.Primary Outcome
Title OL; Mean Change From Baseline to Day 729 in Electrolytes
Hide Description Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN
Time Frame Baseline (Day 1), Day 729
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 124 127 102
Mean (Standard Error)
Unit of Measure: mEq/L
Na -1.10  (0.28) -1.12  (0.29) -1.22  (0.38)
K -0.03  (0.04) -0.04  (0.04) -0.02  (0.04)
Cl -1.31  (0.26) -1.28  (0.31) -2.03  (0.29)
20.Primary Outcome
Title OL; Mean Change From Baseline to Day 729 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Hide Description Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;
Time Frame Baseline (Day 1), Day 729
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 124 127 102
Mean (Standard Error)
Unit of Measure: mg/dL
Creatinine (n=124, n=127, n=102) 0.08  (0.02) 0.08  (0.01) 0.07  (0.02)
BUN (n=124, n=127, n=102) -0.37  (0.43) -0.12  (0.44) 0.20  (0.46)
Ca (n=124, n=127, n=102) 0.01  (0.04) -0.01  (0.05) 0.02  (0.05)
P (n=124, n=127, n=102) -0.05  (0.05) -0.16  (0.06) -0.08  (0.06)
Uric Acid (n=124, n=127, n=102) -0.22  (0.08) -0.02  (0.09) -0.10  (0.12)
Total bilirubin (n=124, n=127, n=101) 0.01  (0.02) 0.04  (0.02) 0.03  (0.02)
Serum glucose (n=123, n=126, n=101) 9.92  (3.04) 7.52  (2.02) 3.74  (2.17)
21.Primary Outcome
Title OL; Mean Change From Baseline to Day 729 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
Hide Description alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN
Time Frame Baseline (Day 1), Day 729
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 124 127 102
Mean (Standard Error)
Unit of Measure: U/L
ALT 2.73  (1.59) 1.02  (1.83) -0.89  (1.96)
AST 0.03  (1.17) -0.22  (1.22) -2.45  (1.60)
GGT 1.23  (2.38) -0.41  (2.14) -1.93  (2.95)
ALP -0.55  (2.17) -2.61  (2.83) -3.91  (3.41)
22.Primary Outcome
Title OL; Mean Change From Baseline to Day 1121 in Hemoglobin, Total Protein, and Albumin
Hide Description Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN
Time Frame Baseline (Day 1), Day 1121
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 102 98 86
Mean (Standard Error)
Unit of Measure: g/dL
HGB (n=102, n=98, n=85) 0.66  (0.13) 0.53  (0.14) 0.57  (0.13)
Total protein (n=102, n=98, n=86) -0.35  (0.05) -0.24  (0.05) -0.33  (0.05)
Albumin (n=102, n=98, n=86) 0.04  (0.04) 0.08  (0.04) -0.01  (0.04)
23.Primary Outcome
Title OL; Mean Change From Baseline to Day 1121 in Platelets
Hide Description Platelets (PLT): <0.67 x LLN, >1.5 x ULN
Time Frame Baseline (Day 1), Day 1121
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 101 95 85
Mean (Standard Error)
Unit of Measure: 10^9 c/L
-67.5  (7.49) -66.1  (8.86) -62.5  (8.05)
24.Primary Outcome
Title OL; Mean Change From Baseline to Day 1121 in Hematocrit
Hide Description Hematocrit: <0.75 x BL
Time Frame Baseline (Day 1), Day 1121
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 100 98 85
Mean (Standard Error)
Unit of Measure: percentage of red blood cells
1.83  (0.37) 1.50  (0.39) 1.47  (0.39)
25.Primary Outcome
Title OL; Mean Change From Baseline to Day 1121 in White Blood Cells
Hide Description Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.
Time Frame Baseline (Day 1), Day 1121
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 102 98 85
Mean (Standard Error)
Unit of Measure: 10^3 c/uL
Leukocytes (n=102, n=98, n=85) -1.07  (0.27) -1.09  (0.26) -0.99  (0.25)
Neutrophils + bands (n=99, n=96, n=84) -1.17  (0.25) -1.40  (0.25) -1.28  (0.24)
Basophils (n=99, n=96, n=85) 0.00  (0.00) 0.00  (0.00) 0.00  (0.00)
Monocytes (n=99, n=96, n=84) 0.03  (0.02) 0.00  (0.03) 0.01  (0.03)
Eosinophils (n=99, n=96, n=84) 0.00  (0.01) -0.06  (0.02) -0.04  (0.02)
Lymphocytes (n=99, n=96, n=84) 0.16  (0.08) 0.34  (0.07) 0.32  (0.10)
26.Primary Outcome
Title OL; Mean Change From Baseline to Day 1121 in Erythrocytes
Hide Description Erythrocytes: <0.75 x BL
Time Frame Baseline (Day 1), Day 1121
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 102 98 85
Mean (Standard Error)
Unit of Measure: 10^6 c/uL
0.11  (0.03) 0.11  (0.04) 0.12  (0.04)
27.Primary Outcome
Title OL; Mean Change From Baseline to Day 1121 in Electrolytes
Hide Description Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN
Time Frame Baseline (Day 1), Day 1121
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 102 98 86
Mean (Standard Error)
Unit of Measure: mEq/L
Na (n=102, n=98, n=86) -1.80  (0.33) -1.38  (0.38) -1.34  (0.42)
K (n=102, n=98, n=85) 0.01  (0.04) 0.08  (0.05) 0.01  (0.05)
Cl (n=102, n=98, n=86) -0.88  (0.35) -0.94  (0.38) -1.42  (0.37)
28.Primary Outcome
Title OL; Mean Change From Baseline to Day 1121 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Hide Description Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;
Time Frame Baseline (Day 1), Day 1121
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 102 98 86
Mean (Standard Error)
Unit of Measure: mg/dL
Creatinine (n=102, n=98, n=86) 0.06  (0.02) 0.07  (0.03) 0.08  (0.02)
BUN (n=102, n=98, n=86) -0.04  (0.49) 0.34  (0.73) 0.20  (0.56)
Ca (n=102, n=98, n=86) -0.01  (0.05) -0.03  (0.06) 0.04  (0.05)
P (n=102, n=98, n=85) -0.18  (0.07) -0.19  (0.07) -0.11  (0.06)
Uric Acid (n=102, n=98, n=86) -0.05  (0.11) 0.13  (0.10) 0.20  (0.15)
Total bilirubin (n=102, n=98, n=86) 0.02  (0.02) 0.03  (0.02) 0.03  (0.02)
Serum glucose (n=101, n=98, n=85) 12.99  (3.31) 6.91  (2.10) 9.07  (3.20)
29.Primary Outcome
Title OL; Mean Change From Baseline to Day 1121 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
Hide Description alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN
Time Frame Baseline (Day 1), Day 1121
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 102 98 86
Mean (Standard Error)
Unit of Measure: U/L
ALT (n=102, n=98, n=86) 4.74  (1.95) 4.66  (2.88) -0.35  (2.33)
AST (n=102, n=98, n=86) 3.79  (1.60) 4.49  (2.13) 0.38  (1.69)
GGT (n=102, n=98, n=86) 1.60  (2.79) -2.88  (2.16) -0.14  (3.79)
ALP (n=88, n=79, n=69) 1.25  (2.62) -4.03  (3.79) -7.35  (3.53)
30.Primary Outcome
Title OL; Mean Change From Baseline to Day 1513 in Hemoglobin, Total Protein, and Albumin
Hide Description Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN
Time Frame Baseline (Day 1), Day 1513
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 23 20 16
Mean (Standard Error)
Unit of Measure: g/dL
HGB 0.25  (0.33) 0.44  (0.31) 0.56  (0.32)
Total protein -0.73  (0.09) -0.33  (0.11) -0.34  (0.14)
Albumin -0.06  (0.07) 0.10  (0.07) 0.00  (0.11)
31.Primary Outcome
Title OL; Mean Change From Baseline to Day 1513 in Platelets
Hide Description Platelets (PLT): <0.67 x LLN, >1.5 x ULN
Time Frame Baseline (Day 1), Day 1513
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 23 19 16
Mean (Standard Error)
Unit of Measure: 10^9 c/L
-78.0  (17.20) -74.0  (16.18) -99.2  (19.83)
32.Primary Outcome
Title OL; Mean Change From Baseline to Day 1513 in Hematocrit
Hide Description Hematocrit: <0.75 x BL
Time Frame Baseline (Day 1), Day 1513
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 23 19 16
Mean (Standard Error)
Unit of Measure: percentage of red blood cells
0.92  (1.00) 1.28  (0.92) 1.18  (1.00)
33.Primary Outcome
Title OL; Mean Change From Baseline to Day 1513 in White Blood Cells
Hide Description Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.
Time Frame Baseline (Day 1), Day 1513
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 23 20 16
Mean (Standard Error)
Unit of Measure: 10^3 c/uL
Leukocytes (n=23, n=20, n=16) -0.34  (0.45) -1.08  (0.63) -2.13  (0.50)
Neutrophils + bands (n=22, n=17, n=16) -0.37  (0.33) -1.03  (0.68) -1.93  (0.50)
Basophils (n=22, n=17, n=16) 0.00  (0.01) -0.01  (0.01) -0.01  (0.01)
Monocytes (n=22, n=17, n=16) 0.01  (0.03) -0.10  (0.09) -0.05  (0.04)
Eosinophils (n=22, n=17, n=16) 0.04  (0.06) -0.11  (0.16) -0.23  (0.00)
Lymphocytes (n=22, n=17, n=16) 0.20  (0.14) 0.16  (0.16) -0.15  (0.16)
34.Primary Outcome
Title OL; Mean Change From Baseline to Day 1513 in Erythrocytes
Hide Description Erythrocytes: <0.75 x BL
Time Frame Baseline (Day 1), Day 1513
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 23 19 16
Mean (Standard Error)
Unit of Measure: 10^6 c/uL
-0.10  (0.09) 0.00  (0.09) -0.09  (0.08)
35.Primary Outcome
Title OL; Mean Change From Baseline to Day 1513 in Electrolytes
Hide Description Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN
Time Frame Baseline (Day 1), Day 1513
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 23 20 16
Mean (Standard Error)
Unit of Measure: mEq/L
Na (n=22, n=20, n=16) -4.36  (0.73) -3.80  (0.99) -4.50  (0.74)
K (n=23, n=20, n=16) -0.16  (0.10) -0.32  (0.08) -0.46  (0.11)
Cl (n=23, n=20, n=16) -2.48  (0.71) -2.60  (0.84) -4.13  (0.88)
36.Primary Outcome
Title OL; Mean Change From Baseline to Day 1513 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Hide Description Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;
Time Frame Baseline (Day 1), Day 1513
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 23 20 16
Mean (Standard Error)
Unit of Measure: mg/dL
Creatinine 0.10  (0.02) 0.05  (0.04) 0.08  (0.06)
BUN 2.87  (0.90) -0.40  (1.13) 0.63  (1.36)
Ca 0.27  (0.07) 0.38  (0.09) 0.35  (0.12)
P -0.09  (0.11) -0.51  (0.16) -0.17  (0.13)
Uric Acid 0.03  (0.18) 0.06  (0.21) 0.33  (0.33)
Total bilirubin 0.08  (0.10) 0.09  (0.03) 0.23  (0.14)
Serum glucose 8.87  (3.19) 9.00  (1.88) 8.44  (4.38)
37.Primary Outcome
Title OL; Mean Change From Baseline to Day 1513 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
Hide Description alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN
Time Frame Baseline (Day 1), Day 1513
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 23 20 16
Mean (Standard Error)
Unit of Measure: U/L
ALT -1.87  (2.73) -9.20  (3.75) 2.44  (8.07)
AST -1.35  (1.72) -2.85  (2.55) 0.38  (7.23)
GGT -3.00  (2.99) -10.9  (5.79) -3.06  (10.30)
ALP -15.8  (5.23) -18.7  (7.12) -11.30  (7.80)
38.Primary Outcome
Title OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Hide Description Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP), units=mm mercury (Hg)
Time Frame Days 365, 729, 1121, and 1513
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.n=number of participants with data available.
Arm/Group Title ABA + MTX [OL]
Hide Arm/Group Description:
All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
Overall Number of Participants Analyzed 372
Mean (Standard Deviation)
Unit of Measure: mm mercury (Hg)
Day 365 SBP pre-dose (n=343) 119.0  (15.03)
Day 365 SBP post-dose (n=341) 118.8  (15.35)
Day 729 SBP pre-dose (n=321) 120.4  (15.20)
Day 729 SBP post-dose (n=323) 119.5  (15.02)
Day 1121 SBP pre-dose (n=265) 121.1  (15.59)
Day 1121 SBP post-dose (n=265) 119.2  (13.99)
Day 1513 SBP pre-dose (n=52) 114.6  (13.57)
Day 1513 SBP post-dose (n=52) 114.2  (12.90)
Day 365 DBP pre-dose (n=343) 74.5  (9.80)
Day 365 DBP post-dose (n=341) 74.0  (10.18)
Day 729 DBP pre-dose (n=321) 74.9  (9.69)
Day 729 DBP post-dose (n=323) 74.6  (9.92)
Day 1121 DBP pre-dose (n=265) 74.9  (9.45)
Day 1121 DBP post-dose (n=265) 73.6  (9.12)
Day 1513 DBP pre-dose (n=52) 71.7  (9.45)
Day 1513 DBP post-dose (n=52) 72.1  (9.11)
39.Primary Outcome
Title OL; Mean Heart Rate (HR) During Open Label Period
Hide Description Heart Rate (HR), units=beats per minute (bpm)
Time Frame Days 365, 729, 1121, and 1513
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.n=number of participants with data available.
Arm/Group Title ABA + MTX [OL]
Hide Arm/Group Description:
All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
Overall Number of Participants Analyzed 372
Mean (Standard Deviation)
Unit of Measure: beats per minute (bpm)
Day 365 HR pre-dose (n=343) 74.2  (9.30)
Day 365 HR post-dose (n=341) 74.1  (8.57)
Day 729 HR pre-dose (n=322) 74.2  (9.12)
Day 729 HR post-dose (n=324) 73.4  (8.59)
Day 1121 HR pre-dose (n=265) 73.9  (9.31)
Day 1121 HR post-dose (n=265) 73.8  (9.46)
Day 1513 HR pre-dose (n=52) 73.0  (8.38)
Day 1513 HR post-dose (n=52) 73.8  (7.16)
40.Primary Outcome
Title OL; Mean Temperature (T) During Open Label Period
Hide Description Temperature (T), units=degrees Celcius
Time Frame Days 365, 729, 1121, and 1513
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.n=number of participants with data available.
Arm/Group Title ABA + MTX [OL]
Hide Arm/Group Description:
All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
Overall Number of Participants Analyzed 372
Mean (Standard Deviation)
Unit of Measure: degrees Celsius
Day 365 T pre-dose (n=339) 36.3  (0.43)
Day 365 T post-dose (n=339) 36.3  (0.41)
Day 729 T pre-dose (n=320) 36.3  (0.45)
Day 729 T post-dose (n=323) 36.3  (0.42)
Day 1121 T pre-dose (n=263) 36.2  (0.51)
Day 1121 T post-dose (n=264) 36.2  (0.47)
Day 1513 T pre-dose (n=52) 36.1  (0.35)
Day 1513 T post-dose (n=52) 36.1  (0.37)
41.Secondary Outcome
Title DB; Adjusted Mean Change From Baseline to Day 197 in DAS 28 Score (ESR) For INF Versus PLA (LOCF Analysis)
Hide Description The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.
Time Frame Baseline (Day 1), 6 months (Day 197)
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.
Arm/Group Title INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 156 102
Mean (Standard Error)
Unit of Measure: units on a scale
-2.25  (0.12) -1.48  (0.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection INF + MTX [DB], PLA + MTX [DB]
Comments Infliximab versus placebo were compared for changes from baseline to 6 months (Day 197) in the DAS28. This comparison was done using an analysis of covariance (ANCOVA) model with treatment group as the effect and baseline value as the covariate. A 95% confidence interval was computed for the treatment difference within the framework of the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean change from baseline
Estimated Value -0.77
Confidence Interval (2-Sided) 95%
-1.14 to -0.39
Estimation Comments [Not Specified]
42.Secondary Outcome
Title DB; DAS 28 (ESR) Area Under The Curve (AUC) Over 12 Months For ABA Versus INF
Hide Description The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). Clinically significant response= decrease in DAS28 score of >1.2 from baseline. DAS28 AUC can be calculated from the DAS28 score versus time curve, which provides an assessment of changes in disease activity over time.
Time Frame From Day 1 through Day 365 (12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.
Arm/Group Title ABA + MTX [DB[ INF + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 150 156
Mean (Standard Deviation)
Unit of Measure: units on a scale
1638.6  (395.81) 1657.5  (460.52)
43.Secondary Outcome
Title DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 197
Hide Description The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
Time Frame DB Day 197
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 156 165 110
Measure Type: Number
Unit of Measure: percentage of participants
61.5 58.8 40.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX [DB], PLA + MTX [DB]
Comments Comparisons were made between ABA and PLA at Day 197 using a continuity corrected Chi-square test. All tests and confidence intervals for treatment comparison were two-sided.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimate of difference from placebo
Estimated Value 20.6
Confidence Interval (2-Sided) 95%
7.7 to 33.6
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection INF + MTX [DB], PLA + MTX [DB]
Comments Comparisons were made between INF and PLA at Day 197 using a continuity corrected Chi-square test. All tests and confidence intervals for treatment comparison were two-sided.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimate of difference from placebo
Estimated Value 17.9
Confidence Interval (2-Sided) 95%
5.1 to 30.7
Estimation Comments [Not Specified]
44.Secondary Outcome
Title DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 365
Hide Description The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
Time Frame DB Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Overall Number of Participants Analyzed 156 165 110
Measure Type: Number
Unit of Measure: percentage of participants
57.7 52.7 57.3
45.Secondary Outcome
Title DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis)
Hide Description The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
Time Frame Baseline (Day 1), 6 months (Day 197)
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 156 164 109
Mean (Standard Error)
Unit of Measure: units on a scale
HAQ-DI -0.69  (0.05) -0.61  (0.05) -0.31  (0.06)
HAQ-DI component: activities -0.61  (0.06) -0.54  (0.06) -0.22  (0.08)
HAQ-DI component: dressing and grooming -0.69  (0.06) -0.57  (0.06) -0.37  (0.07)
HAQ-DI component: eating -0.79  (0.06) -0.77  (0.06) -0.36  (0.08)
HAQ-DI component: grip -0.73  (0.07) -0.70  (0.07) -0.26  (0.08)
HAQ-DI component: hygiene -0.64  (0.07) -0.48  (0.07) -0.26  (0.08)
HAQ-DI component: reach -0.72  (0.07) -0.64  (0.07) -0.30  (0.08)
HAQ-DI component: arising -0.70  (0.06) -0.68  (0.06) -0.39  (0.07)
HAQ-DI component: walking -0.58  (0.06) -0.56  (0.06) -0.23  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX [DB], PLA + MTX [DB]
Comments Adjusted mean change in HAQ-DI from baseline to 6 months (Day 197) was compared between ABA and PLA. This comparison was done using an analysis of covariance (ANCOVA) model with treatment group as the effect and baseline value as the covariate. A 95% confidence interval was computed for the treatment difference within the framework of the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from placebo
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-0.53 to -0.23
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection INF + MTX [DB], PLA + MTX [DB]
Comments Adjusted mean change in HAQ-DI from baseline to 6 months (Day 197) was compared between INF and PLA. This comparison was done using an analysis of covariance (ANCOVA) model with treatment group as the effect and baseline value as the covariate. A 95% confidence interval was computed for the treatment difference within the framework of the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from placebo
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-0.45 to -0.15
Estimation Comments [Not Specified]
46.Secondary Outcome
Title DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis)
Hide Description The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
Time Frame Baseline (Day 1), 12 months (Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all participants randomized into the study receiving study medication, grouped according to randomization treatment. All participants randomized but never receiving study medication excluded. Although 3 participants in PLA group discontinued before Day 197, 2 of these patients were included in the LOCF analysis.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Overall Number of Participants Analyzed 156 164 109
Mean (Standard Error)
Unit of Measure: units on a scale
HAQ-DI -0.67  (0.05) -0.59  (0.05) -0.56  (0.06)
HAQ-DI component: activities -0.55  (0.07) -0.52  (0.07) -0.55  (0.08)
HAQ-DI component: dressing and grooming -0.72  (0.06) -0.60  (0.06) -0.56  (0.07)
HAQ-DI component: eating -0.80  (0.06) -0.73  (0.06) -0.71  (0.08)
HAQ-DI component: grip -0.77  (0.07) -0.64  (0.07) -0.56  (0.08)
HAQ-DI component: hygiene -0.53  (0.07) -0.45  (0.07) -0.42  (0.09)
HAQ-DI component: reach -0.77  (0.07) -0.66  (0.07) -0.53  (0.08)
HAQ-DI component: arising -0.68  (0.06) -0.64  (0.06) -0.61  (0.07)
HAQ-DI component: walking -0.54  (0.06) -0.55  (0.06) -0.47  (0.07)
47.Secondary Outcome
Title DB; Adjusted Mean Change From Baseline to Day 197 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)
Hide Description The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.
Time Frame Baseline (Day 1), 6 months (Day 197)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population, all participants randomized into the study receiving study medication. Participants grouped according to the treatment to which they were randomized. All randomized participants who never received study medication were excluded. SF-36 component scores were not presented in tabular form.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 154 163 109
Mean (Standard Error)
Unit of Measure: units on a scale
SF-36 Physical Component Summary 8.36  (0.69) 7.66  (0.67) 4.34  (0.82)
SF-36 Mental Component Summary 5.14  (0.79) 4.32  (0.76) 1.64  (0.93)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX [DB], PLA + MTX [DB]
Comments Adjusted mean change in SF-36 physical component summary from baseline to 6 months (Day 197) was compared between ABA and PLA. This comparison was done using an analysis of covariance (ANCOVA) model with treatment group as the effect and baseline value as the covariate. A 95% confidence interval was computed for the treatment difference within the framework of the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from placebo (PCS)
Estimated Value 4.02
Confidence Interval (2-Sided) 95%
1.92 to 6.12
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ABA + MTX [DB], PLA + MTX [DB]
Comments Adjusted mean change in SF-36 mental component summary from baseline to 6 months (Day 197) was compared between ABA and PLA. This comparison was done using an analysis of covariance (ANCOVA) model with treatment group as the effect and baseline value as the covariate. A 95% confidence interval was computed for the treatment difference within the framework of the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from placebo (MCS)
Estimated Value 3.51
Confidence Interval (2-Sided) 95%
1.10 to 5.91
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection INF + MTX [DB], PLA + MTX [DB]
Comments Adjusted mean change in SF-36 physical component summary from baseline to 6 months (Day 197) was compared between INF and PLA. This comparison was done using an analysis of covariance (ANCOVA) model with treatment group as the effect and baseline value as the covariate. A 95% confidence interval was computed for the treatment difference within the framework of the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from placebo (PCS)
Estimated Value 3.32
Confidence Interval (2-Sided) 95%
1.25 to 5.40
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection INF + MTX [DB], PLA + MTX [DB]
Comments Adjusted mean change in SF-36 mental component summary from baseline to 6 months (Day 197) was compared between INF and PLA. This comparison was done using an analysis of covariance (ANCOVA) model with treatment group as the effect and baseline value as the covariate. A 95% confidence interval was computed for the treatment difference within the framework of the ANCOVA model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.027
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from placebo (MCS)
Estimated Value 2.68
Confidence Interval (2-Sided) 95%
0.31 to 5.05
Estimation Comments [Not Specified]
48.Secondary Outcome
Title DB; Adjusted Mean Change From Baseline to Day 365 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)
Hide Description The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.
Time Frame Baseline (Day 1), 12 months (Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: all participants randomized into the study receiving study medication, grouped according to randomization treatment. Although 3 participants in PLA group discontinued before Day 197, 2 of these patients were included in the LOCF analysis. SF-36 component scores were not presented in tabular form.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Overall Number of Participants Analyzed 154 163 109
Mean (Standard Error)
Unit of Measure: units on a scale
SF-36 Physical Component Summary 9.52  (0.70) 7.59  (0.68) 8.00  (0.83)
SF-36 Mental Component Summary 5.96  (0.81) 4.03  (0.79) 5.85  (0.97)
49.Secondary Outcome
Title DB; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) at Day 365
Hide Description The DAS28 is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= > 5.1, low disease activity= < 3.2, and remission= < 2.6. Clinically significant response= decrease of >1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from baseline [BL]), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: >5.1 or <0.6 change from BL)
Time Frame DB Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Overall Number of Participants Analyzed 150 157 102
Measure Type: Number
Unit of Measure: percentage of participants
No response 27.3 36.3 23.5
Moderate response 40.7 45.2 49.0
Good response 32.0 18.5 27.5
50.Secondary Outcome
Title DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 197
Hide Description The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein [CRP]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.
Time Frame DB Day 197
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 156 165 110
Measure Type: Number
Unit of Measure: percentage of participants
Day 197, ACR 20 66.7 59.4 41.8
Day 197, ACR 50 40.4 37.0 20.0
Day 197, ACR 70 20.5 24.2 9.1
51.Secondary Outcome
Title DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 365
Hide Description The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein [CRP]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.
Time Frame DB Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Overall Number of Participants Analyzed 156 165 110
Measure Type: Number
Unit of Measure: percentage of participants
Day 365, ACR 20 72.4 55.8 68.2
Day 365, ACR 50 45.5 36.4 50.9
Day 365, ACR 70 26.3 20.6 29.1
52.Secondary Outcome
Title DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, and AEs Leading to Discontinuation From Day 1 Through Day 197
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
Hide Outcome Measure Data
Hide Analysis Population Description
The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 156 165 110
Measure Type: Number
Unit of Measure: participants
Deaths 1 1 0
SAEs 8 19 13
Related SAEs 3 8 3
SAEs Leading to Discontinuation 2 4 0
AEs 129 140 92
Related AEs 64 74 46
AEs Leading to discontinuation 3 8 1
53.Secondary Outcome
Title DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 197
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
Time Frame From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
Hide Outcome Measure Data
Hide Analysis Population Description
The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 156 165 110
Measure Type: Number
Unit of Measure: participants
Pre-specified infections 12 18 8
Neoplasms: Benign, malignant, and unspecified 1 2 1
Prespecified autoimmune symptoms and disorders 1 1 1
Pre-specified infusional AEs 8 30 11
54.Secondary Outcome
Title DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, and AEs Leading to Discontinuation From Day 1 Through Day 365
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study
Hide Outcome Measure Data
Hide Analysis Population Description
The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 156 165
Measure Type: Number
Unit of Measure: participants
Deaths 1 2
SAEs 15 30
Related SAEs 5 14
SAEs Leading to Discontinuation 4 6
AEs 139 154
Related AEs 72 96
AEs Leading to discontinuation 5 12
55.Secondary Outcome
Title DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, and AEs Leading to Discontinuation From Day 198 Through Day 365 in Participants Receiving Placebo Switched to Abatacept
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame From Day 198 through Day 365, and up to 56 days after last dose if occurring on-study
Hide Outcome Measure Data
Hide Analysis Population Description
The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.
Arm/Group Title PLA Switched to ABA + MTX [DB]
Hide Arm/Group Description:
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Overall Number of Participants Analyzed 110
Measure Type: Number
Unit of Measure: participants
Deaths 1
SAEs 12
Related SAEs 3
SAEs Leading to Discontinuation 0
AEs 71
Related AEs 26
AEs Leading to discontinuation 0
56.Secondary Outcome
Title DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 365
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
Time Frame From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study
Hide Outcome Measure Data
Hide Analysis Population Description
The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 156 165
Measure Type: Number
Unit of Measure: participants
Pre-specified infections 16 30
Neoplasms:Benign, malignant, and unspecified 1 2
Prespecified autoimmune symptoms and disorders 2 1
Pre-specified infusional AEs 11 41
57.Secondary Outcome
Title DB; Number of Participants With AEs of Special Interest From Day 198 Through Day 365 in Participants Receiving Placebo Switched to Abatacept
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
Time Frame From Day 198 through Day 365, and up to 56 days after last dose if occurring on-study
Hide Outcome Measure Data
Hide Analysis Population Description
The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.
Arm/Group Title PLA Switched to ABA + MTX [DB]
Hide Arm/Group Description:
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Overall Number of Participants Analyzed 110
Measure Type: Number
Unit of Measure: participants
Pre-specified infections 3
Prespecified autoimmune symptoms and disorders 1
Pre-specified infusional AEs 5
58.Secondary Outcome
Title DB; Number of Participants With Significant Changes in Mean Systolic and Diastolic Blood Pressure During Days 1 Through 197 and Days 1 Through 365
Hide Description Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
Time Frame From Baseline (Day 1) through Day 197, or Day 1 through Day 365, and up to 56 days after last dose if occurring on-study
Hide Outcome Measure Data
Hide Analysis Population Description
As-Treated Population
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 156 165 110
Measure Type: Number
Unit of Measure: participants
Days 1-197 0 0 0
Days 1-365 0 0 0
59.Secondary Outcome
Title DB; Number of Participants With Significant Changes in Mean Heart Rate During Days 1 Through 197 and Days 1 Through 365
Hide Description Heart Rate (HR) was assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
Time Frame From Baseline (Day 1) through Day 197, or Day 1 through Day 365, and up to 56 days after last dose if occurring on-study
Hide Outcome Measure Data
Hide Analysis Population Description
As Treated Population.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 156 165 110
Measure Type: Number
Unit of Measure: participants
Days 1-197 0 0 0
Days 1-365 0 0 0
60.Secondary Outcome
Title DB; Number of Participants With Significant Changes in Mean Temperature During Days 1 Through 197 and Days 1 Through 365
Hide Description Temperature (T) was assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
Time Frame From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
Hide Outcome Measure Data
Hide Analysis Population Description
As Treated Population.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 156 165 110
Measure Type: Number
Unit of Measure: participants
Days 1-197 0 0 0
Days 1-365 0 0 0
61.Secondary Outcome
Title DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197
Hide Description High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; creatinine: >4 x BL
Time Frame From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
Hide Outcome Measure Data
Hide Analysis Population Description
The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 155 162 108
Measure Type: Number
Unit of Measure: participants
Low HGB (n=155, n=162, n=108) 1 1 1
Low hematocrit (n=155, n=162, n=108) 0 2 0
Low PLT (n=154, n=160, n=108) 1 2 0
High PLT (n=154, n=160, n=108) 0 0 1
Low leukocytes (n=155, n=162, n=108) 0 1 0
High leukocytes (n=155, n=162, n=108) 6 12 16
Low neutrophils + bands (n=155, n=162, n=108) 0 0 1
High AST (n=155, n=162, n=108) 3 3 1
High ALT (n=155, n=162, n=108) 3 2 3
High creatinine (n=155, n=162, n=108) 6 9 5
62.Secondary Outcome
Title DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365
Hide Description High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; creatinine: >4 x BL
Time Frame From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study
Hide Outcome Measure Data
Hide Analysis Population Description
The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA Switched to ABA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Overall Number of Participants Analyzed 156 164 109
Measure Type: Number
Unit of Measure: participants
Low HGB (n=156, n=164, n=109) 2 1 1
Low hematocrit (n=156, n=164, n=109) 1 2 0
Low PLT (n=155, n=162, n=109) 1 2 0
High PLT (n=155, n=162, n=109) 0 0 1
Low leukocytes (n=156, n=164, n=109) 0 1 0
High leukocytes (n=156, n=164, n=109) 7 22 20
Low neutrophils + bands (n=156, n=164, n=109) 0 0 1
High AST (n=156, n=164, n=109) 4 6 3
High ALT (n=156, n=164, n=109) 3 7 5
High creatinine (n=156, n=164, n=109) 10 13 7
63.Secondary Outcome
Title DB; Number of Participants With Anti-Abatacept Antibodies From Day 1 Through Day 365 (Electrochemiluminescent [ECL] Immunoassay)
Hide Description ECL screened sera for drug-specific antibodies, immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction Category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing.
Time Frame Day 1 through day 365
Hide Outcome Measure Data
Hide Analysis Population Description
The immunogenicity analysis population included participants who received at least one dose of abatacept and had immunogenicity samples collected at baseline and at least one post-baseline treatment visit.
Arm/Group Title ABA + MTX [DB] PLA Switched to ABA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Overall Number of Participants Analyzed 156 110
Measure Type: Number
Unit of Measure: participants
CTLA4 and Possibly Ig 0 0
Ig and/or Junction 0 0
64.Secondary Outcome
Title DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Hide Description Infliximab levels were measured using a microplate enzyme-linked immunosorbant assay (ELISA) with infliximab bound to immobilized recombinant tumor necrosis factor (TNF)-alpha. Bound infliximab is detected utilizing a horseradish peroxidase-conjugated anti-human IgG Fc(fragment, crystallizable region)-specific). The enzyme turns over the substrate O-phenlenediamine to a chromogenic product that is measured at 490 nm. The cut-off value was 1.40 ug/mL; this was based on the mean (+ 3 SD) value in serum samples from 40 participants who had never received infliximab.
Time Frame Day 1 through day 365
Hide Outcome Measure Data
Hide Analysis Population Description
The immunogenicity analysis population included participants who received at least one dose of infliximab and had immunogenicity samples collected at baseline and at least one post-baseline treatment visit.
Arm/Group Title INF + MTX [DB]
Hide Arm/Group Description:
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 163
Measure Type: Number
Unit of Measure: percentage of participants
Overall anti-HACA 62.0
Overall indeterminate anti-HACA 73.0
Day 1 anti-HACA 0
Day 1 indeterminate anti-HACA 3.7
Day 113 anti-HACA 20.0
Day 113 indeterminate anti-HACA 74.7
Day 197 anti-HACA 42.2
Day 197 indeterminate anti-HACA 33.3
Day 309 anti-HACA 53.6
Day 309 indeterminate anti-HACA 29.7
Post Day 28 anti-HACA 52.2
Post Day 28 indeterminate anti-HACA 27.5
Discontinued, overall anti-HACA 60.9
Discontinued, overall indeterminate anti-HACA 47.8
Discontinued, post day 28 anti-HACA 55.0
Discontinued, post day 28 indeterminate anti-HACA 25.0
Discontinued, post day 56 anti-HACA 72.7
Discontinued, post day 56 indeterminate anti-HACA 9.1
Discontinued, post day 85 anti-HACA 88.9
Discontinued, post day 85 indeterminate anti-HACA 0
Missed doses, overall anti-HACA 73.1
Missed doses, overall indeterminate anti-HACA 76.9
Missed 1 dose, anti-HACA 72.0
Missed 1 dose, indeterminate anti-HACA 76.0
Missed >1 dose, anti-HACA 100.0
Missed >1 dose, indeterminate anti-HACA 100.0
65.Secondary Outcome
Title OL; Mean Change From Baseline Over Time in DAS 28 (ESR) Score
Hide Description The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.
Time Frame Baseline (Day 1), Day 365, Day 533, Day 729
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period.n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants <60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants >100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 132 136 104
Mean (Standard Error)
Unit of Measure: units on a scale
Day 365 (n=122, n=130, n=94) -3.12  (0.13) -2.39  (0.13) -2.81  (0.16)
Day 533 (n=118, n=121, n=92) -3.21  (0.13) -3.04  (0.13) -2.84  (0.17)
Day 729 (n=110, n=121, n=93) -3.35  (0.14) -3.29  (0.12) -2.98  (0.17)
66.Secondary Outcome
Title OL; Percentage of Participants With DAS28 (ESR) Remission and Low Disease Activity (LDAS) Over Time
Hide Description The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.
Time Frame Baseline (Day 1), Day 365, Day 533, Day 729
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Efficacy data was summarized for the 3 DB treatment cohorts.n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants <60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants >100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 132 136 104
Measure Type: Number
Unit of Measure: percentage of participants
Day 365 Remission (n=127, n=135, n=102) 19.7 13.3 15.7
Day 365 LDAS (n=127, n=135, n=102) 37.0 23.0 29.4
Day 533 Remission (n=122, n=125, n=98) 20.5 20.0 19.4
Day 533 LDAS (n=122, n=125, n=98) 37.7 33.6 35.7
Day 729 Remission (n=115, n=126, n=100) 26.1 28.6 22.0
Day 729 LDAS (n=115, n=126, n=100) 41.7 45.2 34.0
67.Secondary Outcome
Title OL; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Over Time
Hide Description The DAS28 is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= > 5.1, low disease activity= < 3.2, and remission= < 2.6. Clinically significant response= decrease of >1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute <3.2 or >1.2 improvement from baseline [BL]), moderate (absolute 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute >5.1 or <0.6 change from BL)
Time Frame DB Days 365, 533, and 729
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period.n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Overall Number of Participants Analyzed 132 136 104
Measure Type: Number
Unit of Measure: percentage of participants
Day 365 Good response (n=122, n=130, n=94) 38.5 23.1 30.9
Day 365 Moderate response (n=122, n=130, n=94) 53.3 58.5 55.3
Day 365 No response (n=122, n=130, n=94) 8.2 18.5 13.8
Day 533 Good response (n=118, n=121, n=92) 38.1 33.1 35.9
Day 533 Moderate response (n=118, n=121, n=92) 58.5 58.7 53.3
Day 533 No response (n=118, n=121, n=92) 3.4 8.3 10.9
Day 729 Good response (n=110, n=121, n=93) 41.8 45.5 34.4
Day 729 Moderate response (n=110, n=121, n=93) 53.6 47.9 51.6
Day 729 No response (n=110, n=121, n=93) 4.5 6.6 14.0
68.Secondary Outcome
Title OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time
Hide Description The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein [CRP]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.
Time Frame DB Day 197, Day 365, Day 533, Day 729
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Overall Number of Participants Analyzed 132 136 104
Measure Type: Number
Unit of Measure: percentage of participants
Day 197, ACR 20 (n=130, n=133, n=102) 73.1 68.4 44.1
Day 197, ACR 50 (n=129, n=134, n=103) 45.7 42.5 21.4
Day 197, ACR 70 (n=130, n=133, n=103) 23.1 27.1 10.7
Day 365, ACR 20 (n=130, n=136, n=103) 88.5 69.1 75.7
Day 365, ACR 50 (n=131, n=136, n=102) 55.0 43.4 54.9
Day 365, ACR 70 (n=131, n=136, n=102) 31.3 23.5 31.4
Day 533, ACR 20 (n=128, n=128, n=102) 82.8 82.8 74.5
Day 533, ACR 50 (n=129, n=128, n=103) 58.1 57.0 47.6
Day 533, ACR 70 (n=129, n=127, n=102) 35.7 40.9 32.4
Day 729, ACR 20 (n=119, n=127, n=102) 86.6 84.3 76.5
Day 729, ACR 50 (n=117, n=127, n=101) 60.7 70.9 49.5
Day 729, ACR 70 (n=120, n=127, n=100) 40.8 44.9 33.0
69.Secondary Outcome
Title OL; Percentage of Participants Who Achieved Major Clinical Response
Hide Description Major Clinical Response was defined as a continuous ACR 70 for six months.
Time Frame Defined from the date of achieving ACR 70 response to 6 months post response
Hide Outcome Measure Data
Hide Analysis Population Description
Protocol-specified analyses of the proportion of participants achieving a Major Clinical Response were not performed since ACR responses in the open-label period could only be assessed at 6-month intervals due to the fact that CRP and ESR were only measured every 6 months during this period.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]
Hide Arm/Group Description:
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants <60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants >100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
70.Secondary Outcome
Title OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time
Hide Description The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
Time Frame OL Days 197, 253, 281, 309, 337, 365, 449, 533, 617, and 729
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period.n=number of participants with data available.
Arm/Group Title ABA + MTX [DB] INF + MTX [DB] PLA + MTX [DB]