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Phase III Study of BMS-188667 (CTLA4Ig) in Patients With Rheumatoid Arthritis Who Are Currently Failing Anti-TNF Therapy or Who Have Failed Anti-TNF Therapy in the Past.

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ClinicalTrials.gov Identifier: NCT00048581
Recruitment Status : Completed
First Posted : November 13, 2002
Results First Posted : June 23, 2011
Last Update Posted : November 21, 2011
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: Abatacept
Drug: Placebo
Enrollment 738
Recruitment Details  
Pre-assignment Details 738 participants were enrolled and 393 participants were randomized. Two participants were randomized in error and were not treated.
Arm/Group Title Abatacept (ABA) Placebo (PLA) Open-label ABA
Hide Arm/Group Description Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes. Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141. All participants who completed the double-blind period were eligible to continue in the open-label period. At the beginning of the open-label period (Day 169), all eligible participants were re-allocated to a 10 mg/kg weight-tiered dose of abatacept at their enrollment visit into the open-label period, based on their entry weight into the study. Participant dose was adjusted based on annual anniversary weight. Participants weighing > 100 kg received 1 g, participants weighing ≥ 60 kg and ≤ 100 kg received 750 mg, and participants weighing < 60 kg received 500 mg on a background of DMARDs (at discretion of the investigator). Concomitant biologic RA therapies were later excluded.
Period Title: Double-Blind Period
Started 258 133 0
Completed 223 99 0
Not Completed 35 34 0
Reason Not Completed
Adverse Event             9             5             0
Lack of Efficacy             14             27             0
Lost to Follow-up             5             0             0
Withdrawal by Subject             5             2             0
Participant Has History of Lymphopenia             1             0             0
Investigator Decision             1             0             0
Period Title: Open-Label Period
Started 0 0 317
Completed 0 0 150
Not Completed 0 0 167
Reason Not Completed
Death             0             0             4
Adverse Event             0             0             37
Lack of Efficacy             0             0             69
Lost to Follow-up             0             0             14
Withdrawal by Subject             0             0             20
No Longer Meets Study Criteria             0             0             2
Poor/Non-compliance             0             0             5
Pregnancy             0             0             7
Study Site Closure             0             0             2
Continue ABA With Primary Rheumatologist             0             0             3
Problem With Transportation To Site             0             0             1
Primary Investigator Retired             0             0             2
Study Ended By Sponsor             0             0             1
Arm/Group Title Abatacept (ABA) Placebo (PLA) Total
Hide Arm/Group Description Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes. Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141. Total of all reporting groups
Overall Number of Baseline Participants 258 133 391
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 258 participants 133 participants 391 participants
53.4  (12.4) 52.7  (11.3) 53.2  (12.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 258 participants 133 participants 391 participants
Female
199
  77.1%
106
  79.7%
305
  78.0%
Male
59
  22.9%
27
  20.3%
86
  22.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 258 participants 133 participants 391 participants
American Indian or Alaska Native
1
   0.4%
1
   0.8%
2
   0.5%
Asian
0
   0.0%
2
   1.5%
2
   0.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
9
   3.5%
5
   3.8%
14
   3.6%
White
248
  96.1%
124
  93.2%
372
  95.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
   0.8%
1
   0.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 258 participants 133 participants 391 participants
North America 189 99 288
Europe 69 34 103
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 258 participants 133 participants 391 participants
78.2  (19.0) 78.2  (21.0) 78.2  (19.7)
1.Primary Outcome
Title Double-blind Period (DB); Number of Participants With American College of Rheumatology (ACR) 20 Response at Day 169
Hide Description ACR 20 response requires a participant to have a 20% reduction in the number of swollen and tender joints, and a reduction of 20% in three of the following five parameters: physician global assessment of disease, participant global assessment of disease, participant assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in Health Assessment Questionnaire (HAQ) score. A participant achieved a sustained ACR 20 response if the participant had ACR 20 observed for at least 2 consecutive study visits.
Time Frame Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was carried out on the intent-to-treat (ITT) population defined as all randomized participants who received at least one dose of study medication. Two participants were unevaluable for response due to each missing 2 infusions of study drug.
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Measure Type: Number
Unit of Measure: participants
129 26
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments The first coprimary endpoint efficacy analysis tested for differences in ACR 20 response rate (RR) between the treatment arm receiving ABA plus background DMARDs and the treatment arm receiving placebo plus background DMARDs on Day 169. A 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test was used to compare these two treatment groups at the .05 level of significance, with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The a priori threshold for statistical significance was 5%. ACR 20 RR at 6 mos for PLA was expected to be ~25%. A sample of 256 in the ABA arm and 128 in PLA arm will yield a 96% power to detect a difference of 20% in ACR 20 at 5% significance level.
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of weighted difference (Est of Weighted Diff)
Method of Estimation Estimation Parameter Est. Weighted. Diff: Day 169 ACR 20
Estimated Value 30.8
Confidence Interval (2-Sided) 95%
20.6 to 41.1
Estimation Comments Differences in ACR response between the two treatment groups represent the weighted average of the individual stratum differences.
2.Primary Outcome
Title DB; Number of Participants Achieving Clinically Meaningful Improvement in Health Assessment Questionnaire (HAQ)
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 Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was carried out on the intent-to-treat (ITT) population defined as all randomized subjects who received at least one dose of study medication. Two participants were unevaluable for response due to each missing 2 infusions of study drug.
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Measure Type: Number
Unit of Measure: participants
121 31
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments The two primary efficacy analyses tested first for differences in ACR 20 followed by testing HAQ response rates between the treatment arm receiving ABA plus background DMARDs and the treatment arm receiving PLA plus background DMARDs on Day 169. A 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test was used to compare these two treatment groups at the .05 level of significance, with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments If the ACR20 analysis was not significant (5% level), then the comparison for HAQ response was not undertaken. If ACR20 comparison was significant (5% level), then CMH Chi-square test compared HAQ response between groups (5% level).
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of weighted difference (Est of Weighted Diff)
Method of Estimation Estimation Parameter Est. of Weighted Diff: Day 169 HAQ
Estimated Value 24.0
Confidence Interval (2-Sided) 95%
13.8 to 34.2
Estimation Comments All comparisons of changes from baseline and construction of confidence intervals for continuous measures were based on an ANCOVA model with treatment as the main factor and baseline value as covariate.
3.Primary Outcome
Title Open-Label Period (OL); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or 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 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.Related AE/SAE=Certain,Probable,Possible,or Missing relationship to Drug
Time Frame From first day of OL to 5.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Open-label ABA
Hide Arm/Group Description:
All participants who completed the double-blind period were eligible to continue in the open-label period. At the beginning of the open-label period (Day 169), all eligible participants were re-allocated to a 10 mg/kg weight-tiered dose of abatacept at their enrollment visit into the open-label period, based on their entry weight into the study. Participant dose was adjusted based on annual anniversary weight. Participants weighing > 100 kg received 1 g, participants weighing ≥ 60 kg and ≤ 100 kg received 750 mg, and participants weighing < 60 kg received 500 mg on a background of DMARDs (at discretion of the investigator). Concomitant biologic RA therapies were later excluded.
Overall Number of Participants Analyzed 317
Measure Type: Number
Unit of Measure: participants
Deaths 6
SAEs 136
Related SAEs 24
SAEs Leading to Discontinuation 20
AEs 302
Related AEs 192
AEs Leading to Discontinuation 34
4.Primary Outcome
Title OL; Number of Participants 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, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).
Time Frame From first day of OL to 5.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Open-label ABA
Hide Arm/Group Description:
All participants who completed the double-blind period were eligible to continue in the open-label period. At the beginning of the open-label period (Day 169), all eligible participants were re-allocated to a 10 mg/kg weight-tiered dose of abatacept at their enrollment visit into the open-label period, based on their entry weight into the study. Participant dose was adjusted based on annual anniversary weight. Participants weighing > 100 kg received 1 g, participants weighing ≥ 60 kg and ≤ 100 kg received 750 mg, and participants weighing < 60 kg received 500 mg on a background of DMARDs (at discretion of the investigator). Concomitant biologic RA therapies were later excluded.
Overall Number of Participants Analyzed 317
Measure Type: Number
Unit of Measure: participants
Infections 254
Neoplasms (benign, malignant, and unspecified) 42
Malignancies 21
Pre-specified autoimmune disorders 17
Acute infusional AEs 65
Peri-infusional AEs 22
5.Primary Outcome
Title OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
Hide Description Upper Normal Limit (ULN), Lower Normal Limit (LLN), Baseline (BL). Marked abnormality criteria are: Hemoglobin (HGB): >3 g/dL decrease from BL; Hematocrit: <0.75 * BL; Erythrocytes: <0.75 * BL; Platelets (PLT): <0.67 * LLN/>1.5 * ULN, or if BL < LLN then use 0.5 * BL/<100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL<LLN then use <0.8 * BL/>ULN, or if BL>ULN then use >1.2 * BL/<LLN; neutrophils+bands: <1.0 * 10^3 c/uL; eosinophils: >0.750 * 10^3 c/uL; basophils: > 400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750 * 10^3 c/uL/ >7.50 * 10^3 c/uL.
Time Frame From first day of OL to 5.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Open-label ABA
Hide Arm/Group Description:
All participants who completed the double-blind period were eligible to continue in the open-label period. At the beginning of the open-label period (Day 169), all eligible participants were re-allocated to a 10 mg/kg weight-tiered dose of abatacept at their enrollment visit into the open-label period, based on their entry weight into the study. Participant dose was adjusted based on annual anniversary weight. Participants weighing > 100 kg received 1 g, participants weighing ≥ 60 kg and ≤ 100 kg received 750 mg, and participants weighing < 60 kg received 500 mg on a background of DMARDs (at discretion of the investigator). Concomitant biologic RA therapies were later excluded.
Overall Number of Participants Analyzed 315
Measure Type: Number
Unit of Measure: participants
Low HGB (LLN=11.5 g/dL) 12
Low hematocrit (LLN=34%) 18
Low erythrocytes (LLN=3.8 x10*6 cells/μL) 9
Low PLT (LLN=140*10^9 cells/L) 8
High PLT (ULN=450*10^9 cells/L) 1
Low leukocytes (LLN=3.8*10^3 cells/μL) 6
High leukocytes (ULN=10.6*10^3 c/μL) 49
Low neutrophils + bands (LLN=1.8*10^3 c/μL)) 2
Low lymphocytes (LLN=0.7*10^3 cells/μL) 61
High lymphocytes (ULN=4.5*10^3 cells/μL) 0
High monocytes (ULN=1*10^3 cells/μL) 2
High basophils (ULN=0.2*10^3 cells/μL) 0
High eosinophils (ULN=7*10^3 cells/μL) 31
6.Primary Outcome
Title OL; Number of Participants With Blood Chemistry Laboratories Meeting Marked Abnormality Criteria
Hide Description Marked abnormality criteria: Alkaline phosphatase (ALP): >2* ULN, or if BL>ULN then use >3* BL; aspartate aminotransferase (AST): >3* ULN, or if BL>ULN then use >4* BL; alanine aminotransferase (ALT): >3* ULN, or if BL>ULN then use >4* BL; G-Glutamyl transferase (GGT): >2* ULN, or if BL>ULN then use >3* BL; Bilirubin: >2* ULN, or if BL>ULN then use >4* BL; blood urea nitrogen (BUN): >2* BL; creatinine: >1.5* BL
Time Frame From first day of OL to 5.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Open-label ABA
Hide Arm/Group Description:
All participants who completed the double-blind period were eligible to continue in the open-label period. At the beginning of the open-label period (Day 169), all eligible participants were re-allocated to a 10 mg/kg weight-tiered dose of abatacept at their enrollment visit into the open-label period, based on their entry weight into the study. Participant dose was adjusted based on annual anniversary weight. Participants weighing > 100 kg received 1 g, participants weighing ≥ 60 kg and ≤ 100 kg received 750 mg, and participants weighing < 60 kg received 500 mg on a background of DMARDs (at discretion of the investigator). Concomitant biologic RA therapies were later excluded.
Overall Number of Participants Analyzed 315
Measure Type: Number
Unit of Measure: participants
High ALP (ULN=400 U/L) 3
High AST (ULN=44 U/L) 12
High ALT (ULN=55 U/L) 12
High GGT (ULN=65 U/L) 30
High bilirubin (ULN=1.2 mg/dL) 2
High BUN (ULN=26 mg/dL) 20
High creatinine (ULN=1.5 mg/dL) 77
7.Primary Outcome
Title OL; Mean Time-matched Baseline Immunoglobulin (Ig) Levels Over the OL
Hide Description Serum samples collected from participants were used to determine serum levels of IgA, IgM, and IgG. Time-matched baseline values were presented by visit and represented the mean baseline value for only that cohort of participants with serum samples available at that visit.
Time Frame Baseline and Days 169, 365, 729, and 1093
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with available serum samples. N=the total number of participants analyzed, n=the number of participants at that time point with available serum samples. Mean time-matched baseline values reflect changing n-values over time.
Arm/Group Title OL: ABA OL: PLA
Hide Arm/Group Description:
Participants treated in the OL who were randomized to receive placebo on a background of DMARDs in the DB. Participants weighing > 100 kg received 1 g, participants weighing ≥ 60 kg and ≤ 100 kg received 750 mg, and participants weighing < 60 kg received 500 mg on a background of DMARDs IV on Days 1, 15, 29, 57, 85, 113, and 141.
Participants treated in the OL who were randomized to receive placebo on a background of DMARDs in the DB. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 201 96
Mean (Standard Deviation)
Unit of Measure: mg/dL
Day 169 cohort (n=201, n=96): IgA 327.9  (170.8) 326.9  (203.3)
Day 169 cohort (n=201, n=96): IgG 1346.0  (473.0) 1364.0  (532.2)
Day 169 cohort (n=201, n=96): IgM 180.1  (128.3) 160.1  (86.91)
Day 365 cohort (n=182, n=84): IgA 337.6  (173.0) 318.6  (204.4)
Day 365 cohort (n=182, n=84): IgG 1320.0  (421.2) 1341.0  (525.9)
Day 365 cohort (n=182, n=84): IgM 175.7  (113.5) 159.5  (88.33)
Day 729 cohort (n=163, n=75): IgA 322.2  (156.8) 327.6  (218.5)
Day 729 cohort (n=163, n=75): IgG 1337.0  (421.4) 1338.0  (528.7)
Day 729 cohort (n=163, n=75): IgM 184.1  (137.0) 165.9  (91.12)
Day 1093 cohort (n=76, n=42): IgG 294.1  (128.6) 329.6  (167.8)
Day 1093 cohort (n=76, n=42): IgG 1374.0  (537.3) 1478.0  (562.9)
Day 1093 cohort (n=76, n=42): IgM 175.5  (158.1) 174.2  (89.43)
8.Primary Outcome
Title OL; Mean Time-matched Change From Baseline in Immunoglobulin (Ig) Levels Over the OL
Hide Description Serum samples collected from participants were used to determine serum levels of IgA, IgM, and IgG. Time-matched mean change from baseline = Post-baseline value - time-matched baseline value, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with serum samples available at that visit.
Time Frame BL, Days 169, 365, 729, and 1093
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with available serum samples. N=the total number of participants analyzed, n=the number of participants at that time point with available serum samples. Mean time-matched baseline values reflect changing n-values over time.
Arm/Group Title OL: ABA OL: PLA
Hide Arm/Group Description:
Participants treated in the OL who were randomized to receive placebo on a background of DMARDs in the DB. Participants weighing > 100 kg received 1 g, participants weighing ≥ 60 kg and ≤ 100 kg received 750 mg, and participants weighing < 60 kg received 500 mg on a background of DMARDs IV on Days 1, 15, 29, 57, 85, 113, and 141.
Participants treated in the OL who were randomized to receive placebo on a background of DMARDs in the DB. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 201 96
Mean (Standard Error)
Unit of Measure: mg/dL
Day 169 cohort (n=201, n=96): IgA -35.3  (3.61) 1.10  (8.12)
Day 169 cohort (n=201, n=96): IgG -233.0  (19.54) -72.8  (35.74)
Day 169 cohort (n=201, n=96): IgM -17.8  (3.59) -5.42  (3.63)
Day 365 cohort (n=182, n=84): IgA -37.5  (4.93) -33.0  (10.12)
Day 365 cohort (n=182, n=84): IgG -282.0  (18.60) -251.0  (39.41)
Day 365 cohort (n=182, n=84): IgM -23.0  (4.21) -18.3  (4.21)
Day 729 cohort (n=163, n=75): IgA -37.3  (6.13) -30.0  (10.42)
Day 729 cohort (n=163, n=75): IgG -344.0  (2.81) -257.0  (38.30)
Day 729 cohort (n=163, n=75): IgM -19.4  (6.01) -16.1  (6.02)
Day 1093 cohort (n=76, n=41): IgA -35.6  (7.50) -69.4  (16.83)
Day 1093 cohort (n=76, n=42): IgG -396.0  (46.77) -377.0  (55.94)
Day 1093 cohort (n=76, n=42): IgM -29.7  (9.03) -24.7  (9.51)
9.Secondary Outcome
Title DB; Number of Participants With ACR 20, ACR 50, and ACR 70 Responses Over Time
Hide Description ACR 20/50/70 response requires a participant to have a 20/50/70% reduction in the number of swollen and tender joints, and a reduction of 20/50/70% in three of the following five parameters: physician global assessment of disease, participant global assessment of disease, participant assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in Health Assessment Questionnaire (HAQ) score. A participant achieved a sustained ACR 20/50/70 response if the participant had ACR 20/50/70 observed for at least 2 consecutive study visits.
Time Frame Days 15, 29, 57, 85, 113, 141, and 169
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was carried out on the intent-to-treat (ITT) population defined as all randomized subjects who received at least one dose of study medication. Two participants were unevaluable for response due to each missing 2 infusions of study drug. N=Number of Participants Analyzed, n=number of participants at visit
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Measure Type: Number
Unit of Measure: participants
Day 15 ACR 20 45 7
Day 15 ACR 50 6 0
Day 15 ACR 70 2 0
Day 29 ACR 20 84 25
Day 29 ACR 50 22 4
Day 29 ACR 70 6 1
Day 57 ACR 20 118 32
Day 57 ACR 50 34 9
Day 57 ACR 70 13 0
Day 85 ACR 20 118 24
Day 85 ACR 50 46 8
Day 85 ACR 70 15 1
Day 113 ACR 20 126 31
Day 113 ACR 50 46 5
Day 113 ACR 70 20 0
Day 141 ACR 20 141 26
Day 141 ACR 50 65 6
Day 141 ACR 70 26 0
Day 169 ACR 20 129 26
Day 169 ACR 50 52 5
Day 169 ACR 70 26 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in ACR 20 between the treatment arm receiving ABA plus background DMARDs and the treatment arm receiving PLA plus background DMARDs were compared using a 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test (.05 level of significance), with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of difference (Est of Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 15 ACR 20
Estimated Value 12.3
Confidence Interval (2-Sided) 95%
4.6 to 20.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments If ACR20 comparison was significant (5% level), then CMH Chi-square test compared ACR 50 response between groups (5% level). If the ACR20 analysis was not significant (5% level), then the comparison for ACR 50 response was not undertaken. A 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test was used to compare these two treatment groups at the .05 level of significance, with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of difference (Est of Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 15 ACR 50
Estimated Value 2.3
Confidence Interval (2-Sided) 95%
-0.8 to 5.5
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments If ACR20 comparison was significant (5% level), then CMH Chi-square test compared ACR 70 response between groups (5% level). If the ACR20 analysis was not significant (5% level), then the comparison for ACR 70 response was not undertaken. A 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test was used to compare these two treatment groups at the .05 level of significance, with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.784
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of difference (Est of Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 15 ACR 70
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-1.3 to 2.9
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in ACR 20 between the treatment arm receiving ABA plus background DMARDs and the treatment arm receiving PLA plus background DMARDs were compared using a 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test (.05 level of significance), with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of difference (Est of Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 29 ACR 20
Estimated Value 14.0
Confidence Interval (2-Sided) 95%
4.0 to 24.0
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments If ACR20 comparison was significant (5% level), then CMH Chi-square test compared ACR 50 response between groups (5% level). If the ACR20 analysis was not significant (5% level), then the comparison for ACR 50 response was not undertaken. A 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test was used to compare these two treatment groups at the .05 level of significance, with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.06
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of difference (Est of Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 29 ACR 50
Estimated Value 5.6
Confidence Interval (2-Sided) 95%
-0.2 to 11.4
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments If ACR20 comparison was significant (5% level), then CMH Chi-square test compared ACR 70 response between groups (5% level). If the ACR20 analysis was not significant (5% level), then the comparison for ACR 70 response was not undertaken. A 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test was used to compare these two treatment groups at the .05 level of significance, with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.473
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of difference (Est of Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 29 ACR 70
Estimated Value 1.6
Confidence Interval (2-Sided) 95%
-1.8 to 4.9
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in ACR 20 between the treatment arm receiving ABA plus background DMARDs and the treatment arm receiving PLA plus background DMARDs were compared using a 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test (.05 level of significance), with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of difference (Est of Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 57 ACR 20
Estimated Value 22.0
Confidence Interval (2-Sided) 95%
11.3 to 32.8
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments If ACR20 comparison was significant (5% level), then CMH Chi-square test compared ACR 50 response between groups (5% level). If the ACR20 analysis was not significant (5% level), then the comparison for ACR 50 response was not undertaken. A 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test was used to compare these two treatment groups at the .05 level of significance, with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.076
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of difference (Est of Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 57 ACR 50
Estimated Value 6.5
Confidence Interval (2-Sided) 95%
-0.6 to 13.7
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments If ACR20 comparison was significant (5% level), then CMH Chi-square test compared ACR 70 response between groups (5% level). If the ACR20 analysis was not significant (5% level), then the comparison for ACR 70 response was not undertaken. A 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test was used to compare these two treatment groups at the .05 level of significance, with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of difference (Est of Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 57 ACR 70
Estimated Value 5.1
Confidence Interval (2-Sided) 95%
0.7 to 9.4
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in ACR 20 between the treatment arm receiving ABA plus background DMARDs and the treatment arm receiving PLA plus background DMARDs were compared using a 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test (.05 level of significance), with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of difference (Est of Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 85 ACR 20
Estimated Value 28.0
Confidence Interval (2-Sided) 95%
17.4 to 38.7
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments If ACR20 comparison was significant (5% level), then CMH Chi-square test compared ACR 50 response between groups (5% level). If the ACR20 analysis was not significant (5% level), then the comparison for ACR 50 response was not undertaken. A 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test was used to compare these two treatment groups at the .05 level of significance, with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of difference (Est of Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 85 ACR 50
Estimated Value 12.0
Confidence Interval (2-Sided) 95%
4.1 to 19.8
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments If ACR20 comparison was significant (5% level), then CMH Chi-square test compared ACR 70 response between groups (5% level). If the ACR20 analysis was not significant (5% level), then the comparison for ACR 70 response was not undertaken. A 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test was used to compare these two treatment groups at the .05 level of significance, with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of difference (Est of Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 85 ACR 70
Estimated Value 5.1
Confidence Interval (2-Sided) 95%
0.4 to 9.8
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in ACR 20 between the treatment arm receiving ABA plus background DMARDs and the treatment arm receiving PLA plus background DMARDs were compared using a 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test (.05 level of significance), with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of weighted difference (Est of Weighted Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 113 ACR 20
Estimated Value 25.9
Confidence Interval (2-Sided) 95%
15.1 to 36.8
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments If ACR20 comparison was significant (5% level), then CMH Chi-square test compared ACR 50 response between groups (5% level). If the ACR20 analysis was not significant (5% level), then the comparison for ACR 50 response was not undertaken. A 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test was used to compare these two treatment groups at the .05 level of significance, with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of weighted difference (Est of Weighted Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 113 ACR 50
Estimated Value 14.2
Confidence Interval (2-Sided) 95%
6.6 to 21.9
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments If ACR20 comparison was significant (5% level), then CMH Chi-square test compared ACR 70 response between groups (5% level). If the ACR20 analysis was not significant (5% level), then the comparison for ACR 70 response was not undertaken. A 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test was used to compare these two treatment groups at the .05 level of significance, with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of weighted difference (Est of Weighted Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 113 ACR 70
Estimated Value 7.8
Confidence Interval (2-Sided) 95%
2.6 to 13.0
Estimation Comments Differences in ACR response between the two treatment groups represent the weighted average of the individual stratum differences.
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in ACR 20 between the treatment arm receiving ABA plus background DMARDs and the treatment arm receiving PLA plus background DMARDs were compared using a 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test (.05 level of significance), with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of difference (Est of Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 141 ACR 20
Estimated Value 35.5
Confidence Interval (2-Sided) 95%
24.6 to 46.5
Estimation Comments Differences in ACR response between the two treatment groups represent the weighted average of the individual stratum differences.
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments If ACR20 comparison was significant (5% level), then CMH Chi-square test compared ACR 50 response between groups (5% level). If the ACR20 analysis was not significant (5% level), then the comparison for ACR 50 response was not undertaken. A 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test was used to compare these two treatment groups at the .05 level of significance, with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of weighted difference (Est of Weighted Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 141 ACR 50
Estimated Value 20.9
Confidence Interval (2-Sided) 95%
12.2 to 29.5
Estimation Comments Differences in ACR response between the two treatment groups represent the weighted average of the individual stratum differences.
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments If ACR20 comparison was significant (5% level), then CMH Chi-square test compared ACR 70 response between groups (5% level). If the ACR20 analysis was not significant (5% level), then the comparison for ACR 70 response was not undertaken. A 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test was used to compare these two treatment groups at the .05 level of significance, with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of weighted difference (Est of Weighted Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 141 ACR 70
Estimated Value 10.2
Confidence Interval (2-Sided) 95%
4.4 to 16.0
Estimation Comments Differences in ACR response between the two treatment groups represent the weighted average of the individual stratum differences.
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in ACR 20 between the treatment arm receiving ABA plus background DMARDs and the treatment arm receiving PLA plus background DMARDs were compared using a 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test (.05 level of significance), with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of difference (Est of Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 169 ACR 20
Estimated Value 30.8
Confidence Interval (2-Sided) 95%
20.0 to 41.7
Estimation Comments Differences in ACR response between the two treatment groups represent the weighted average of the individual stratum differences.
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments If ACR20 comparison was significant (5% level), then CMH Chi-square test compared ACR 50 response between groups (5% level). If the ACR20 analysis was not significant (5% level), then the comparison for ACR 50 response was not undertaken. A 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test was used to compare these two treatment groups at the .05 level of significance, with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of weighted difference (Est of Weighted Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 169 ACR 50
Estimated Value 16.6
Confidence Interval (2-Sided) 95%
8.6 to 24.5
Estimation Comments Differences in ACR response between the two treatment groups represent the weighted average of the individual stratum differences.
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments If ACR20 comparison was significant (5% level), then CMH Chi-square test compared ACR 70 response between groups (5% level). If the ACR20 analysis was not significant (5% level), then the comparison for ACR 70 response was not undertaken. A 2-sided Cochran-Mantel-Haenszel (CMH) Chi-square test was used to compare these two treatment groups at the .05 level of significance, with stratification based on baseline history of anti-TNF status (current or prior use).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments All statistical tests and CI were 2-sided. Percentage of participants with response compared by estimate of difference (Est of Weighted Diff)
Method of Estimation Estimation Parameter Est. of Diff: Day 169 ACR 70
Estimated Value 8.7
Confidence Interval (2-Sided) 95%
2.7 to 14.6
Estimation Comments Differences in ACR response between the two treatment groups represent the weighted average of the individual stratum differences.
10.Secondary Outcome
Title DB; Mean Time-matched Baseline Tender Joint Counts (TJCs) and Post-Baseline TJCs Over Time: ACR Core Component
Hide Description The mean TJC core component of the ACR scoring system was evaluated based on the number of tender joints in a standard 68 joint count, where an increasing number of tender joints indicates increasing level of severity. Time-matched baseline TJC values for each post-baseline TJC in the DB were presented for each visit and represent the mean baseline TJC value for only that cohort of participants with TJCs available at that visit.
Time Frame BL
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all randomized subjects receiving at least 1 dose of study drug. 2 participants were unevaluable for response due to each missing 2 infusions of study drug. N=total number of participants analyzed, n=the number of participants at time point with TJCs. Mean time-matched BL values reflect changing n-values over time.
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Deviation)
Unit of Measure: tender joints
Day 15 cohort (n=251, n=126): baseline 31.33  (12.86) 32.75  (13.13)
Day 15 cohort (n=251, n=126): post-baseline 25.58  (14.39) 30.35  (15.37)
Day 29 cohort (n=248, n=128): baseline 31.41  (13.11) 32.72  (13.06)
Day 29 cohort (n=248, n=128): post-baseline 21.61  (14.53) 27.52  (15.85)
Day 57 cohort (n=251, n=129): baseline 31.17  (12.90) 32.31  (13.14)
Day 57 cohort (n=251, n=129): post-baseline 18.88  (14.41) 24.20  (16.46)
Day 85 cohort (n=249, n=129): baseline 31.42  (13.05) 32.58  (13.10)
Day 85 cohort (n=249, n=129): post-baseline 18.51  (14.15) 25.56  (15.80)
Day 113 cohort (n=246, n=128): baseline 31.32  (13.10) 32.65  (13.15)
Day 113 cohort (n=246, n=128): post-baseline 16.76  (14.18) 25.21  (16.18)
Day 141 cohort (n=252, n=128): baseline 31.34  (13.10) 32.28  (13.21)
Day 141 cohort (n=252, n=128): post-baseline 16.04  (13.89) 23.67  (15.62)
Day 169 cohort (n=254, n=130): baseline 31.33  (13.06) 32.43  (13.16)
Day 169 cohort (n=254, n=130): post-baseline 16.21  (13.94) 25.55  (16.30)
11.Secondary Outcome
Title DB; Mean Time-Matched Percentage of Change From Baseline in TJC Over Time: ACR Core Component
Hide Description The mean TJC core component of the ACR scoring system was evaluated based on the number of tender joints in a standard 68 joint count, where an increasing number of tender joints indicates increasing level of severity. Mean Time-matched percentage of change from baseline = (time-matched baseline value - Post-baseline value)/time-matched baseline value x 100, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with TJCs available at that visit.
Time Frame BL, Days 15, 29, 57, 85, 113, 141, and 169
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all randomized subjects receiving at least 1 dose of study drug. 2 participants were unevaluable for response due to each missing 2 infusions of study drug. N=total number of participants analyzed, n=the number of participants at time point with TJCs. Mean time-matched BL values reflect changing n-values over time.
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Error)
Unit of Measure: percentage of change from BL
Day 15 cohort (n=251, n=126) 19.74  (2.19) 6.43  (3.25)
Day 29 cohort (n=248, n=128) 32.68  (2.41) 14.96  (3.84)
Day 57 cohort (n=251, n=129) 40.52  (2.56) 24.99  (3.62)
Day 85 cohort (n=249, n=129) 40.40  (2.62) 20.94  (3.49)
Day 113 cohort (n=246, n=128) 46.20  (2.76) 21.72  (3.87)
Day 141 cohort (n=252, n=128) 49.06  (2.53) 24.03  (4.05)
Day 169 cohort (n=254, n=130) 47.76  (2.66) 20.04  (3.84)
12.Secondary Outcome
Title DB; Mean Time-matched Baseline Swollen Joint Count (SJC) and Post-Baseline SJCs Over Time: ACR Core Component
Hide Description The mean SJC core component of the ACR scoring system was evaluated based on the number of swollen joints in a standard 66 joint count, where an increasing number of swollen joints indicates increasing level of severity. Time-matched baseline SJC values for each post-baseline SJC in the DB were presented for each visit and represent the mean baseline SJC value for only that cohort of participants with SJCs available at that visit.
Time Frame Days 15, 29, 57, 85, 113, 141, and 169
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all randomized subjects receiving at least 1 dose of study drug. 2 participants were unevaluable for response due to each missing 2 infusions of study drug. N=total number of participants analyzed, n=the number of participants at time point with SJCs. Mean time-matched BL values reflect changing n-values over time.
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Deviation)
Unit of Measure: swollen joints
Day 15 cohort (n=251, n=126): baseline 22.31  (10.08) 22.00  (9.79)
Day 15 cohort (n=251, n=126): post-line 17.88  (10.42) 19.06  (10.97)
Day 29 cohort (n=248, n=128): baseline 22.49  (10.32) 21.86  (9.79)
Day 29 cohort (n=248, n=128): post-baseline 15.55  (10.62) 17.95  (11.83)
Day 57 cohort (n=251, n=129): baseline 22.15  (10.05) 21.80  (9.78)
Day 57 cohort (n=251, n=129): post-baseline 13.44  (9.81) 15.98  (10.17)
Day 85 cohort (n=249, n=129): baseline 22.42  (10.30) 21.81  (9.77)
Day 85 cohort (n=249, n=129): post-baseline 12.44  (9.41) 16.25  (11.92)
Day 113 cohort (n=246, n=128): baseline 22.48  (10.34) 21.82  (9.81)
Day 113 cohort (n=246, n=128): post-baseline 12.18  (10.18) 16.28  (10.78)
Day 141 cohort (n=252, n=128): baseline 22.38  (10.29) 21.63  (9.74)
Day 141 cohort (n=252, n=128): post-baseline 11.06  (8.91) 15.92  (10.49)
Day 169 cohort (n=254, n=130): baseline 22.35  (10.25) 21.77  (9.75)
Day 169 cohort (n=254, n=130): post-baseline 12.00  (9.78) 16.18  (11.10)
13.Secondary Outcome
Title DB; Mean Time-Matched Percentage of Change From Baseline in SJC Over Time: ACR Core Component
Hide Description The mean SJC core component of the ACR scoring system was evaluated based on the number of swollen joints in a standard 66 joint count, where an increasing number of swollen joints indicate increasing level of severity. Mean Time-matched percentage of change from baseline = (time-matched baseline value - Post-baseline value)/time-matched baseline value x 100, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with TJCs available at that visit.
Time Frame Days 15, 29, 57, 85, 113, 141, and 169
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all randomized subjects receiving at least 1 dose of study drug. 2 participants were unevaluable for response due to each missing 2 infusions of study drug. N=total number of participants analyzed, n=the number of participants at time point with SJCs. Mean time-matched BL values reflect changing n-values over time.
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Error)
Unit of Measure: percentage of change from BL
Day 15 cohort (n=251, n=126) 18.64  (2.38) 13.13  (3.03)
Day 29 cohort (n=248, n=128) 32.68  (2.41) 14.96  (3.84)
Day 57 cohort (n=251, n=129) 38.49  (2.70) 24.98  (3.45)
Day 85 cohort (n=249, n=129) 44.42  (2.30) 26.22  (3.72)
Day 113 cohort (n=246, n=128) 45.31  (2.75) 22.87  (3.72)
Day 141 cohort (n=252, n=128) 49.38  (2.42) 24.33  (3.77)
Day 169 cohort (n=254, n=130) 44.26  (2.84) 23.78  (3.87)
14.Secondary Outcome
Title DB; Mean Time-matched Baseline Participant Pain Assessment Over Time: ACR Core Component
Hide Description The participant self-reported pain assessment is a core component of the ACR scoring system where increasing score indicates increasing level of severity as indicated on a 100 mm Visual Analog Scale (VAS) with 0 mm representing no pain and 100 mm representing the most pain possible. For each post-baseline visit in the DB, time-matched baseline Participant Pain Assessment values were presented and represent the mean baseline value for only that cohort of participants with assessments available at that visit.
Time Frame BL
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all randomized subjects receiving at least 1 dose of study drug. 2 participants were unevaluable for response due to each missing 2 infusions of study drug. N=total number of participants analyzed, n=the number of participants at time point with data. Mean time-matched BL values reflect changing n-values over time.
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Deviation)
Unit of Measure: units on a scale
Day 15 cohort (n=247, n=126): baseline 71.09  (19.57) 69.20  (19.02)
Day 15 cohort (n=247, n=126): post-baseline 61.05  (22.45) 67.65  (20.48)
Day 29 cohort (n=240, n=128): baseline 70.45  (19.77) 69.80  (18.76)
Day 29 cohort (n=240, n=128): post-baseline 52.88  (23.93) 61.07  (24.13)
Day 57 cohort (n=246, n=129): baseline 70.72  (19.70) 69.26  (18.79)
Day 57 cohort (n=246, n=129): post-baseline 46.19  (25.26) 55.91  (25.85)
Day 85 cohort (n=245, n=129): baseline 70.87  (19.85) 69.40  (18.92)
Day 85 cohort (n=245, n=129): post-baseline 44.69  (26.13) 60.16  (25.05)
Day 113 cohort (n=239, n=126): baseline 70.93  (19.71) 70.27  (18.54)
Day 113 cohort (n=239, n=126): post-baseline 44.60  (26.19) 60.17  (25.53)
Day 141 cohort (n=249, n=127): baseline 70.85  (19.73) 69.34  (19.02)
Day 141 cohort (n=249, n=127): post-baseline 43.67  (27.20) 59.80  (25.08)
Day 169 cohort (n=251, n=130): baseline 70.89  (19.67) 69.47  (18.86)
Day 169 cohort (n=251, n=130): post-baseline 43.48  (27.76) 62.21  (24.73)
15.Secondary Outcome
Title DB; Mean Time-Matched Percentage of Change From Baseline in Participant Pain Assessment Over Time: ACR Core Component
Hide Description Participant self-reported pain assessment is a core component of the ACR scoring system where increasing score indicates increasing level of severity as indicated on a 100 mm Visual Analog Scale (VAS) with 0 mm representing no pain and 100 mm representing the most pain possible. Mean Time-matched percentage of change from baseline = (time-matched baseline value - Post-baseline value)/time-matched baseline value x 100, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with assessments available at that visit.
Time Frame BL, Days 15, 29, 57, 85, 113, 141, and 169
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all randomized subjects receiving at least 1 dose of study drug. 2 participants were unevaluable for response due to each missing 2 infusions of study drug. N=total number of participants analyzed, n=the number of participants at time point with data. Mean time-matched BL values reflect changing n-values over time.
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Error)
Unit of Measure: percentage of change from BL
Day 15 cohort (n=247, n=126) 8.48  (3.82) -3.19  (3.24)
Day 29 cohort (n=240, n=128) 18.31  (3.51) 8.36  (3.26)
Day 57 cohort (n=246, n=129) 24.58  (6.39) 16.65  (3.28)
Day 85 cohort (n=245, n=129) 26.76  (6.61) 8.59  (3.79)
Day 113 cohort (n=239, n=126) 28.46  (4.79) 9.87  (3.98)
Day 141 cohort (n=249, n=127) 27.29  (6.72) 4.32  (5.55)
Day 169 cohort (n=251, n=130) 28.64  (5.70) 4.36  (4.01)
16.Secondary Outcome
Title DB; Mean Time-matched Baseline HAQ-DI Over Time: ACR Core Component
Hide Description HAQ-DI is a self-administered questionnaire composed of 20 questions assessing physical function in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. 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. The HAQ-DI is the weighted sum of the scale scores, with higher scores indicating poorer function. For each post-BL visit, time-matched BL HAQ-DI values were presented and represent the mean BL value for only that cohort of participants with data available at that visit.
Time Frame BL
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all randomized subjects receiving at least 1 dose of study drug. 2 participants were unevaluable for response due to each missing 2 infusions of study drug. N=total number of participants analyzed, n=the number of participants at time point with data. Mean time-matched BL values reflect changing n-values over time.
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Deviation)
Unit of Measure: units on a scale
Day 15 cohort (n=244, n=124): baseline 1.84  (0.56) 1.86  (0.56)
Day 15 cohort (n=244, n=124): post-baseline 1.69  (0.60) 1.83  (0.56)
Day 29 cohort (n=239, n=127): baseline 1.84  (0.57) 1.85  (0.56)
Day 29 cohort (n=239, n=127): post-baseline 1.59  (0.64) 1.70  (0.62)
Day 57 cohort (n=245, n=127): baseline 1.83  (0.57) 1.84  (0.55)
Day 57 cohort (n=245, n=127): post-baseline 1.49  (0.65) 1.65  (0.63)
Day 85 cohort (n=242, n=126): baseline 1.84  (0.57) 1.86  (0.56)
Day 85 cohort (n=242, n=126): post-baseline 1.45  (0.64) 1.70  (0.63)
Day 113 cohort (n=238, n=126): baseline 1.85  (0.57) 1.85  (0.56)
Day 113 cohort (n=238, n=126): post-baseline 1.44  (0.70) 1.71  (0.64)
Day 141 cohort (n=247, n=126): baseline 1.84  (0.57) 1.86  (0.56)
Day 141 cohort (n=247, n=126): post-baseline 1.41  (0.71) 1.72  (0.64)
Day 169 cohort (n=248, n=128): baseline 1.84  (0.57) 1.85  (0.56)
Day 169 cohort (n=248, n=128): post-baseline 1.38  (0.72) 1.74  (0.63)
17.Secondary Outcome
Title DB; Mean Time-Matched Percentage of Change From Baseline in HAQ-DI Over Time: ACR Core Component
Hide Description A self-administered questionnaire with 20 questions assessing physical function in 8 domains:dressing,arising,eating,walking,hygiene,reach,grip and common activities.Questions evaluated on a 4-point scale:0=without any difficulty,1=with some difficulty,2=with much difficulty,and 3=unable to do. HAQ-DI=weighted sum of scale scores, with higher scores indicating poorer function. Mean time-matched % change from BL=(time-matched BL value - Post-BL value)/time-matched BL value x100, where time-matched BL value=the mean BL value for only that cohort of participants with data available at that visit.
Time Frame BL, Days 15, 29, 57, 85, 113, 141, and 169
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all randomized subjects receiving at least 1 dose of study drug. 2 participants were unevaluable for response due to each missing 2 infusions of study drug. N=total number of participants analyzed, n=the number of participants at time point with data. Mean time-matched BL values reflect changing n-values over time.
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Error)
Unit of Measure: percentage of change from BL
Day 15 cohort (n=244, n=124) 7.94  (1.45) -1.10  (2.99)
Day 29 cohort (n=239, n=127) 13.75  (1.81) 6.79  (2.49)
Day 57 cohort (n=245, n=127) 19.05  (1.78) 9.61  (2.85)
Day 85 cohort (n=242, n=126) 21.00  (1.79) 7.10  (2.68)
Day 113 cohort (n=238, n=126) 22.77  (1.98) 5.96  (3.15)
Day 141 cohort (n=247, n=126) 24.41  (2.16) 6.50  (2.68)
Day 169 cohort (n=248, n=128) 25.48  (2.14) 5.08  (2.84)
18.Secondary Outcome
Title DB; Mean Time-matched Baseline Participant Global Assessment Over Time: ACR Core Component
Hide Description Participant self-reported global RA assessment core component of the ACR scoring system where increasing score indicates increasing level of severity as indicated on a 100 mm Visual Analog Scale (VAS) with 0 mm representing no pain and 100 mm representing the most pain possible. For each post-baseline visit in the DB, time-matched baseline Participant Global Assessment values were presented and represent the mean baseline value for only that cohort of participants with assessments available at that visit.
Time Frame BL
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all randomized subjects receiving at least 1 dose of study drug. 2 participants were unevaluable for response due to each missing 2 infusions of study drug. N=total number of participants analyzed, n=the number of participants at time point with data. Mean time-matched BL values reflect changing n-values over time.
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Deviation)
Unit of Measure: units on a scale
Day 15 cohort (n=247, n=126): baseline 69.30  (19.70) 68.93  (20.38)
Day 15 cohort (n=247, n=126): post-baseline 58.55  (23.50) 65.15  (21.38)
Day 29 cohort (n=240, n=128): baseline 68.86  (19.88) 69.33  (20.03)
Day 29 cohort (n=240, n=128): post-baseline 52.48  (22.56) 61.13  (24.42)
Day 57 cohort (n=246, n=129): baseline 69.02  (19.84) 68.97  (20.10)
Day 57 cohort (n=246, n=129): post-baseline 45.07  (24.16) 56.60  (26.03)
Day 85 cohort (n=245, n=129): baseline 69.40  (19.72) 69.12  (20.23)
Day 85 cohort (n=245, n=129): post-baseline 43.27  (25.65) 60.18  (24.88)
Day 113 cohort (n=239, n=126): baseline 69.40  (19.68) 70.37  (19.15)
Day 113 cohort (n=239, n=126): post-baseline 45.05  (25.36) 58.46  (25.61)
Day 141 cohort (n=249, n=127): baseline 69.09  (19.83) 69.15  (20.36)
Day 141 cohort (n=249, n=127): post-baseline 43.72  (26.65) 59.24  (25.69)
Day 169 cohort (n=251, n=130): baseline 69.22  (19.80) 69.18  (20.16)
Day 169 cohort (n=251, n=130): post-baseline 43.51  (27.19) 60.35  (25.69)
19.Secondary Outcome
Title DB; Mean Time-Matched Percentage of Change From Baseline in Participant Global Assessment Over Time: ACR Core Component
Hide Description Participant self-reported global RA assessment core component of the ACR scoring system where increasing score indicates increasing level of severity as indicated on a 100mm Visual Analog Scale (VAS) with 0mm representing no pain and 100mm representing the most pain possible. Mean Time-matched percentage of change from baseline = (time-matched baseline value - Post-baseline value)/time-matched baseline value x 100, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with assessments available at that visit.
Time Frame BL, Days 15, 29, 57, 85, 113, 141, and 169
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all randomized subjects receiving at least 1 dose of study drug. 2 participants were unevaluable for response due to each missing 2 infusions of study drug. N=total number of participants analyzed, n=the number of participants at time point with data. Mean time-matched BL values reflect changing n-values over time.
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Error)
Unit of Measure: percentage of change from BL
Day 15 cohort (n=247, n=126) 11.54  (2.88) -3.18  (4.48)
Day 29 cohort (n=240, n=128) 18.31  (2.93) 2.13  (5.10)
Day 57 cohort (n=246, n=129) 29.84  (3.19) 10.94  (4.70)
Day 85 cohort (n=245, n=129) 32.03  (4.08) 2.89  (5.42)
Day 113 cohort (n=239, n=126) 30.83  (3.02) 8.01  (5.48)
Day 141cohort (n=249, n=127) 29.46  (4.72) 4.85  (5.51)
Day 169 cohort (n=251, n=130) 30.87  (4.10) 4.52  (5.40)
20.Secondary Outcome
Title DB; Mean Time-matched Baseline Physician Global Assessment Over Time: ACR Core Component
Hide Description Physician global rheumatoid arthritis (RA) assessment core component of the ACR scoring system where increasing score indicates increasing level of severity as indicated on a 100mm Visual Analog Scale (VAS) with 0mm representing no pain and 100mm representing the most pain possible. For each post-baseline visit in the DB, time-matched baseline Physician Global Assessment values were presented and represent the mean baseline value for only that cohort of participants with assessments available at that visit.
Time Frame BL
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all randomized subjects receiving at least 1 dose of study drug. 2 participants were unevaluable for response due to each missing 2 infusions of study drug. N=total number of participants analyzed, n=the number of participants at time point with data. Mean time-matched BL values reflect changing n-values over time.
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Deviation)
Unit of Measure: units on a scale
Day 15 cohort (n=250, n=126): baseline 68.86  (17.40) 66.91  (16.78)
Day 15 cohort (n=250, n=126): post-baseline 54.07  (21.93) 61.43  (19.03)
Day 29 cohort (n=246, n=126): baseline 68.73  (17.41) 66.81  (16.91)
Day 29 cohort (n=246, n=126): post-baseline 44.96  (21.03) 53.71  (23.08)
Day 57 cohort (n=252, n=127): baseline 68.74  (17.34) 66.92  (16.64)
Day 57 cohort (n=252, n=127): post-baseline 41.46  (21.93) 49.21  (25.03)
Day 85 cohort (n=247, n=124):baseline 69.08  (17.42) 66.81  (16.82)
Day 85 cohort (n=247, n=124): post-baseline 37.54  (21.29) 53.06  (25.63)
Day 113 cohort (n=246, n=127): baseline 68.88  (17.26) 67.45  (16.66)
Day 113 cohort (n=246, n=127): post-baseline 37.15  (21.88) 54.49  (24.30)
Day 141 cohort (n=252, n=127): baseline 68.82  (17.39) 67.03  (16.96)
Day 141 cohort (n=252, n=127): post-baseline 34.32  (21.56) 51.58  (24.44)
Day 169 cohort (n=254, n=129): baseline 68.91  (17.40) 67.05  (16.84)
Day 169 cohort (n=254, n=129): post-baseline 36.46  (23.65) 52.37  (25.10)
21.Secondary Outcome
Title DB; Mean Time-Matched Percentage of Change From Baseline in Physician Global Assessment Over Time: ACR Core Component
Hide Description Physician global rheumatoid arthritis (RA) assessment core component of the ACR scoring system where increasing score indicates increasing level of severity as indicated on a 100mm Visual Analog Scale (VAS) with 0mm representing no pain and 100mm representing the most pain possible. Mean Time-matched percentage of change from baseline = (time-matched baseline value - Post-baseline value)/time-matched baseline value x 100, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with assessments available at that visit.
Time Frame BL, Days 15, 29, 57, 85, 113, 141, and 169
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all randomized subjects receiving at least 1 dose of study drug. 2 participants were unevaluable for response due to each missing 2 infusions of study drug. N=total number of participants analyzed, n=the number of participants at time point with data. Mean time-matched BL values reflect changing n-values over time.
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Error)
Unit of Measure: percentage of change from BL
Day 15 cohort (n=250, n=126) 19.27  (2.45) 6.26  (2.47)
Day 29 cohort (n=246, n=126) 32.32  (2.59) 18.00  (3.08)
Day 57 cohort (n=252, n=127) 38.41  (2.38) 25.51  (3.28)
Day 85 cohort (n=247, n=124) 43.74  (2.20) 18.05  (4.04)
Day 113cohort (n=246, n=127) 45.11  (2.02) 17.53  (3.26)
Day 141 cohort (n=252, n=127) 49.35  (1.89) 21.34  (3.35)
Day 169 cohort (n=254, n=129) 45.18  (2.33) 21.28  (3.14)
22.Secondary Outcome
Title DB; Mean Time-matched Baseline C-Reactive Protein (CRP) Levels Over Time: ACR Core Component
Hide Description CRP is an acute phase reactant protein that is a clinical marker for Rheumatoid Arthritis (RA) and a core component of the ACR scoring system. CRP was evaluated from serum samples. Increasing levels of CRP indicate increasing level of disease. For each post-baseline visit in the DB, time-matched baseline CRP values were presented and represent the mean baseline value for only that cohort of participants with assessments available at that visit.
Time Frame BL
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all randomized subjects receiving at least 1 dose of study drug. 2 participants were unevaluable for response due to each missing 2 infusions of study drug. N=total number of participants analyzed, n=the number of participants at time point with data. Mean time-matched BL values reflect changing n-values over time.
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Deviation)
Unit of Measure: mg/dL
Day 15 cohort (n=246, n=127): baseline 4.53  (3.92) 3.97  (3.57)
Day 15 cohort (n=246, n=127): post-baseline 3.20  (3.36) 4.01  (3.54)
Day 29 cohort (n=245, n=128): baseline 4.62  (4.03) 4.03  (3.62)
Day 29 cohort (n=245, n=128): post-baseline 2.70  (2.70) 4.02  (3.63)
Day 57 cohort (n=250, n=129): baseline 4.60  (3.99) 3.93  (3.58)
Day 57 cohort (n=250, n=129): post-baseline 2.39  (2.47) 3.73  (4.06)
Day 85 cohort (n=249, n=129): baseline 4.59  (3.95) 4.00  (3.61)
Day 85 cohort (n=249, n=129): post-baseline 2.36  (3.09) 4.13  (4.11)
Day 113 cohort (n=243, n=127): baseline 4.62  (4.00) 4.06  (3.62)
Day 113 cohort (n=243, n=127): post-baseline 2.26  (3.05) 4.31  (4.62)
Day 141 cohort (n=251, n=129): baseline 4.62  (3.98) 4.03  (3.60)
Day 141 cohort (n=251, n=129): post-baseline 2.20  (3.01) 3.83  (4.17)
Day 169 cohort (n=254, n=131): baseline 4.60  (3.97) 3.99  (3.59)
Day 169 cohort (n=254, n=131): post-baseline 2.31  (3.47) 3.97  (4.19)
23.Secondary Outcome
Title DB; Mean Time-Matched Percentage of Change From Baseline in CRP Levels Over Time: ACR Core Component
Hide Description CRP is an acute phase reactant protein that is a clinical marker for Rheumatoid Arthritis (RA) and a core component of the ACR scoring system. CRP was evaluated from serum samples. Increasing levels indicate increasing level of disease. Mean Time-matched percentage of change from baseline = (time-matched baseline value - Post-baseline value)/time-matched baseline value x 100, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with data available at that visit.
Time Frame Days 15, 29, 57, 85, 113, 141, and 169
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all randomized subjects receiving at least 1 dose of study drug. 2 participants were unevaluable for response due to each missing 2 infusions of study drug. N=total number of participants analyzed, n=the number of participants at time point with data. Mean time-matched BL values reflect changing n-values over time.
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Error)
Unit of Measure: percentage of change from BL
Day 15 cohort (n=246, n=127) 14.03  (6.70) -20.8  (8.24)
Day 29 cohort (n=245, n=128) 24.05  (4.20) -20.1  (6.81)
Day 57 cohort (n=250, n=129) 22.83  (8.55) -14.8  (8.23)
Day 85 cohort (n=249, n=129) 25.87  (9.68) -31.9  (9.82)
Day 113 cohort (n=243, n=127) 34.52  (4.33) -32.1  (10.37)
Day 141 cohort (n=251, n=129) 33.47  (4.76) -22.8  (9.78)
Day 169 cohort (n=254, n=131) 25.05  (8.44) -28.4  (11.82)
24.Secondary Outcome
Title DB; Mean Baseline Levels of Disease Biomarkers (Interleukin-6 (IL-6), Soluble IL-2 Receptor [sIL-2R], and Tumor Necrosing Factor [TNF]-Alpha) in Participants With Measurements at Day 169
Hide Description Potential biomarkers of disease (IL-6, SIL-2R, and TNF-Alpha) were determined from serum samples for all participants. The mean baseline value presented represents a time-matched Day 169 baseline value for only that cohort of participants with assessments available at that visit.
Time Frame BL
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was carried out on the intent-to-treat (ITT) population defined as all randomized subjects who received at least one dose of study medication. Two participants were unevaluable for response due to each missing 2 infusions of study drug. N=Number of Participants Analyzed, n=number of participants at visit
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Deviation)
Unit of Measure: pg/ml
IL-6 (n=194, n=103) 46.19  (62.49) 43.18  (62.90)
sIL-2R (n=193, n=88) 1840  (767.0) 1879  (1001)
TNF-alpha (n=250, n=129) 35.24  (73.17) 30.64  (54.08)
25.Secondary Outcome
Title DB; Mean Change From Baseline to Day 169 in Levels of Disease Biomarkers (IL-6, sIL-2R, and TNF-alpha) in Participants With Measurements at Day 169
Hide Description The mean change from baseline in levels of potential biomarkers of disease (IL-6, SIL-2R, and TNF-Alpha) were determined from serum samples for all participants. Change from Baseline = Post-baseline value – time-matched baseline value, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with data available at Day 169.
Time Frame BL, Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was carried out on the intent-to-treat (ITT) population defined as all randomized subjects who received at least one dose of study medication. Two participants were unevaluable for response due to each missing 2 infusions of study drug. N=Number of Participants Analyzed, n=number of participants at visit
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Error)
Unit of Measure: pg/ml
IL-6 (n=194, n=103) -24.4  (4.54) 4.71  (8.13)
sIL-2R (n=193, n=88) -565  (40.40) -36.1  (77.37)
TNF-alpha (n=250, n=129) -13.5  (4.06) 5.87  (8.27)
26.Secondary Outcome
Title DB; Mean Baseline Levels of Disease Biomarkers (E-Selectin, Soluble Inter-Cellular Adhesion Molecule 1 [sICAM-1], and Matrix Metalloproteinase-3 [MMP-3]) in Participants With Measurements at Day 169
Hide Description Potential biomarkers of disease (E-selectin, sICAM-1, and MMP-3) were determined from serum samples for all participants. The mean baseline value presented represents a time-matched Day 169 baseline value for only that cohort of participants with assessments available at that visit.
Time Frame BL
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was carried out on the intent-to-treat (ITT) population defined as all randomized subjects who received at least one dose of study medication. Two participants were unevaluable for response due to each missing 2 infusions of study drug. N=Number of Participants Analyzed, n=number of participants at visit
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Deviation)
Unit of Measure: ng/ml
E-selectin (n=190, n=103) 93.03  (101.2) 84.53  (71.64)
sICAM-1 (n=187, n=103) 426.6  (218.6) 443.5  (327.1)
MMP3 (n=192, n=133) 86.53  (97.59) 84.18  (133.5)
27.Secondary Outcome
Title DB; Mean Change From Baseline to Day 169 in Levels of Disease Biomarkers (E-Selectin, sICAM-1, and MMP-3) in Participants With Measurements at Day 169
Hide Description Potential biomarkers of disease (E-selectin, sICAM-1, and MMP-3) were determined from serum samples for all participants. Change from Baseline = Post-baseline value – time-matched baseline value, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with data available at Day 169.
Time Frame BL, Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was carried out on the intent-to-treat (ITT) population defined as all randomized subjects who received at least one dose of study medication. Two participants were unevaluable for response due to each missing 2 infusions of study drug. N=Number of Participants Analyzed, n=number of participants at visit
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Error)
Unit of Measure: ng/ml
E-selectin (n=190, n=103) -10.6  (4.97) 6.54  (4.34)
sICAM-1 (n=187, n=103) -22.2  (16.58) -29.5  (20.17)
MMP3 (n=192, n=133) -37.0  (6.42) -9.62  (11.51)
28.Secondary Outcome
Title DB; Mean Change From Baseline to Day 169 in Rheumatoid Factor (RF) Status
Hide Description Rheumatoid factor (RF or RhF) is an autoantibody (antibody directed against an organism's own tissues) most relevant in rheumatoid arthritis. It is an antibody against the Fc portion of Immunoglobulin (Ig)G, which is itself an antibody. RF and IgG join to form immune complexes which contribute to the disease process. A positive value for RF was >20 IU/mL; a negative value for RF was ≤ 20 IU/mL.
Time Frame BL, Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was carried out on the intent-to-treat (ITT) population defined as all randomized subjects who received at least one dose of study medication. Two participants were unevaluable for response due to each missing 2 infusions of study drug. N=Number of Participants Analyzed, n=number of participants at visit
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Measure Type: Number
Unit of Measure: participants
Baseline RF negative 46 25
Baseline RF negative change to RF positive 3 3
Baseline RF positive 154 73
Baseline RF positive change to RF negative 13 0
29.Secondary Outcome
Title DB; Mean Baseline Short Form 36 (SF-36) Quality of Life Physical Component Summary (PCS), Mental Component Summary (MCS), and SF-36 Individual Component Scores For Participants With Measurements at Day 85
Hide Description 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: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. 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. Mean BL value presented represents a time-matched Day 85 BL value for only that cohort of participants with data available at that visit.
Time Frame BL
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was carried out on the intent-to-treat (ITT) population defined as all randomized subjects who received at least one dose of study medication. Two participants were unevaluable for response due to each missing 2 infusions of study drug. N=Number of Participants Analyzed, n=number of participants at visit
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
PCS (n=243, n=128) 27.41  (6.94) 27.77  (6.31)
MCS (n=243, n=128) 41.13  (12.35) 43.00  (11.94)
Physical Function Scale Component (n=246, n=129) 25.94  (8.90) 26.31  (8.36)
Role-Physical Scale Component (n=249, n=129) 30.50  (6.25) 31.96  (6.84)
Bodily Pain Scale Component (n=248, n=129) 30.49  (6.72) 31.28  (6.64)
General Health Scale Component (n=250, n=129) 34.75  (9.18) 34.95  (8.46)
Vitality Scale Component (n=249, n=129) 34.99  (8.51) 36.70  (9.10)
Social Functioning Scale Component (n=250, n=129) 33.06  (10.78) 33.95  (11.49)
Role-Emotional Scale Component (n=249, n=128) 35.79  (13.76) 37.07  (13.83)
Mental Health Scale Component (n=249, n=129) 40.35  (12.75) 42.72  (11.15)
30.Secondary Outcome
Title DB; Adjusted Mean Change From Baseline to Day 85 in Short SF-36 PCS, MCS, and SF-36 Individual Component Scores
Hide Description SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0=worst score (or quality of life) and 100=best score. Change from Baseline= Post-baseline value – time-matched baseline value, where time-matched BL value = the mean BL value for only that cohort of participants with data available at Day 85.
Time Frame BL, Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was carried out on the intent-to-treat (ITT) population defined as all randomized subjects who received at least one dose of study medication. Two participants were unevaluable for response due to each missing 2 infusions of study drug. N=Number of Participants Analyzed, n=number of participants at visit
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Error)
Unit of Measure: Units on a Scale
PCS (n=243, n=128) 5.76  (0.52) 2.12  (0.72)
MCS (n=243, n=128) 4.64  (0.63) 2.08  (0.86)
Physical Function Scale Component (n=246, n=129) 3.97  (0.51) 2.27  (0.71)
Role-Physical Scale Component (n=249, n=129) 5.88  (0.65) 2.87  (0.90)
Bodily Pain Scale Component (n=248, n=129) 8.43  (0.55) 2.81  (0.76)
General Health Scale Component (n=250, n=129) 3.65  (0.45) 1.15  (0.62)
Vitality Scale Component (n=249, n=129) 5.49  (0.57) 2.32  (0.80)
Social Functioning Scale Component (n=250, n=129) 6.83  (0.62) 2.13  (0.87)
Role-Emotional Scale Component (n=249, n=128) 4.12  (0.83) 3.14  (1.16)
Mental Health Scale Component (n=249, n=129) 4.29  (0.58) 1.70  (0.80)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in mean changes from baseline between the 2 treatment groups (ABA and PLA) in PCS, MCS, and the 8 subscale scores at Day 85 were compared using ANCOVA models. Adjusted difference (Adj Diff) from PLA group with 95% CIs and p-values were calculated, and adjustment was based on ANCOVA model with treatment group as factor and baseline value as covariate.
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 Adj Diff: Day 85 PCS
Estimated Value 3.63
Confidence Interval (2-Sided) 95%
1.89 to 5.38
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in mean changes from baseline between the 2 treatment groups (ABA and PLA) in PCS, MCS, and the 8 subscale scores at Day 85 were compared using ANCOVA models. Adjusted difference (Adj Diff) from PLA group with 95% CIs and p-values were calculated, and adjustment was based on ANCOVA model with treatment group as factor and baseline value as covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.017
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adj Diff: Day 85 MCS
Estimated Value 2.57
Confidence Interval (2-Sided) 95%
0.47 to 4.67
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in mean changes from baseline between the 2 treatment groups (ABA and PLA) in PCS, MCS, and the 8 subscale scores at Day 85 were compared using ANCOVA models. Adjusted difference (Adj Diff) from PLA group with 95% CIs and p-values were calculated, and adjustment was based on ANCOVA model with treatment group as factor and baseline value as covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.052
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adj Diff: Day 85 Physical Function
Estimated Value 1.70
Confidence Interval (2-Sided) 95%
-0.01 to 3.41
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in mean changes from baseline between the 2 treatment groups (ABA and PLA) in PCS, MCS, and the 8 subscale scores at Day 85 were compared using ANCOVA models. Adjusted difference (Adj Diff) from PLA group with 95% CIs and p-values were calculated, and adjustment was based on ANCOVA model with treatment group as factor and baseline value as covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adj Diff: Day 85 Role-Physical
Estimated Value 3.01
Confidence Interval (2-Sided) 95%
0.83 to 5.19
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in mean changes from baseline between the 2 treatment groups (ABA and PLA) in PCS, MCS, and the 8 subscale scores at Day 85 were compared using ANCOVA models. Adjusted difference (Adj Diff) from PLA group with 95% CIs and p-values were calculated, and adjustment was based on ANCOVA model with treatment group as factor and baseline value as covariate.
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 Adj Diff: Day 85 Bodily Pain
Estimated Value 5.62
Confidence Interval (2-Sided) 95%
3.77 to 7.47
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in mean changes from baseline between the 2 treatment groups (ABA and PLA) in PCS, MCS, and the 8 subscale scores at Day 85 were compared using ANCOVA models. Adjusted difference (Adj Diff) from PLA group with 95% CIs and p-values were calculated, and adjustment was based on ANCOVA model with treatment group as factor and baseline value as covariate.
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 Adj Diff: General Health
Estimated Value 2.51
Confidence Interval (2-Sided) 95%
0.99 to 4.02
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in mean changes from baseline between the 2 treatment groups (ABA and PLA) in PCS, MCS, and the 8 subscale scores at Day 85 were compared using ANCOVA models. Adjusted difference (Adj Diff) from PLA group with 95% CIs and p-values were calculated, and adjustment was based on ANCOVA model with treatment group as factor and baseline value as covariate.
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 Adj Diff: Day 85 Vitality
Estimated Value 3.17
Confidence Interval (2-Sided) 95%
1.24 to 5.10
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in mean changes from baseline between the 2 treatment groups (ABA and PLA) in PCS, MCS, and the 8 subscale scores at Day 85 were compared using ANCOVA models. Adjusted difference (Adj Diff) from PLA group with 95% CIs and p-values were calculated, and adjustment was based on ANCOVA model with treatment group as factor and baseline value as covariate.
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 Adj Diff: Day 85 Social Functioning
Estimated Value 4.69
Confidence Interval (2-Sided) 95%
2.59 to 6.79
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in mean changes from baseline between the 2 treatment groups (ABA and PLA) in PCS, MCS, and the 8 subscale scores at Day 85 were compared using ANCOVA models. Adjusted difference (Adj Diff) from PLA group with 95% CIs and p-values were calculated, and adjustment was based on ANCOVA model with treatment group as factor and baseline value as covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.494
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adj Diff: Day 85 Role Emotional
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
-1.82 to 3.77
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in mean changes from baseline between the 2 treatment groups (ABA and PLA) in PCS, MCS, and the 8 subscale scores at Day 85 were compared using ANCOVA models. Adjusted difference (Adj Diff) from PLA group with 95% CIs and p-values were calculated, and adjustment was based on ANCOVA model with treatment group as factor and baseline value as covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adj Diff: Day 85 Mental Health
Estimated Value 2.59
Confidence Interval (2-Sided) 95%
0.65 to 4.54
Estimation Comments [Not Specified]
31.Secondary Outcome
Title DB; Mean Baseline SF-36 PCS, MCS, and SF-36 Individual Component Scores For Participants With Measurements at Day 169
Hide Description 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: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. 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. Mean BL value presented represents a time-matched Day 169 BL value for only that cohort of participants with data available at that visit.
Time Frame BL
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was carried out on the intent-to-treat (ITT) population defined as all randomized subjects who received at least one dose of study medication. Two participants were unevaluable for response due to each missing 2 infusions of study drug. N=Number of Participants Analyzed, n=number of participants at visit
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
PCS (n=242, n=129) 27.36  (6.88) 27.75  (6.29)
MCS (n=242, n=129) 41.56  (12.33) 42.98  (11.90)
Physical Function Scale Component (n=247, n=130) 25.96  (8.88) 26.24  (8.37)
Role-Physical Scale Component (n=249, n=130) 30.56  (6.29) 31.93  (6.82)
Bodily Pain Scale Component (n=248, n=130) 30.54  (6.76) 31.27  (6.62)
General Health Scale Component (n=252, n=130) 34.81  (9.20) 35.05  (8.51)
Vitality Scale Component (n=252, n=130) 35.07  (8.52) 36.69  (9.06)
Social Functioning Scale Component (n=251, n=130) 33.17  (10.81) 33.84  (11.52)
Role-Emotional Scale Component (n=249, n=129) 35.96  (13.77) 36.97  (13.83)
Mental Health Scale Component (n=252, n=130) 40.50  (12.81) 42.80  (11.14)
32.Secondary Outcome
Title DB; Adjusted Mean Change From Baseline to Day 169 in SF-36 PCS, MCS, and SF-36 Individual Component Scores For Participants With Measurements at Day 169
Hide Description SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0=worst score (or quality of life) and 100=best score. Change from Baseline= Post-baseline value – time-matched baseline value, where time-matched BL value = the mean BL value for only that cohort of participants with data available at Day 169.
Time Frame BL, Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was carried out on the intent-to-treat (ITT) population defined as all randomized subjects who received at least one dose of study medication. Two participants were unevaluable for response due to each missing 2 infusions of study drug. N=Number of Participants Analyzed, n=number of participants at visit
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
PCS (n=242, n=129) 6.58  (0.55) 1.12  (0.75)
MCS (n=242, n=129) 5.15  (0.64) 2.11  (0.87)
Physical Function Scale Component (n=247, n=130) 5.30  (0.58) 1.27  (0.80)
Role-Physical Scale Component (n=249, n=130) 6.52  (0.63) 1.29  (0.87)
Bodily Pain Scale Component (n=248, n=130) 8.72  (0.56) 2.48  (0.77)
General Health Scale Component (n=252, n=130) 4.02  (0.48) 0.74  (0.67)
Vitality Scale Component (n=252, n=130) 6.55  (0.60) 1.77  (0.83)
Social Functioning Scale Component (n=251, n=130) 7.31  (0.65) 2.39  (0.91)
Role-Emotional Scale Component (n=249, n=129) 6.00  (0.83) 2.46  (1.15)
Mental Health Scale Component (n=252, n=130) 4.31  (0.56) 1.61  (0.79)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in mean changes from baseline between the 2 treatment groups (ABA and PLA) in PCS, MCS, and the 8 subscale scores at Day 85 were compared using ANCOVA models. Adjusted difference (Adj Diff) from PLA group with 95% CIs and p-values were calculated, and adjustment was based on ANCOVA model with treatment group as factor and baseline value as covariate.
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 Adj Diff: Day 169 PCS
Estimated Value 5.46
Confidence Interval (2-Sided) 95%
3.64 to 7.29
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in mean changes from baseline between the 2 treatment groups (ABA and PLA) in PCS, MCS, and the 8 subscale scores at Day 85 were compared using ANCOVA models. Adjusted difference (Adj Diff) from PLA group with 95% CIs and p-values were calculated, and adjustment was based on ANCOVA model with treatment group as factor and baseline value as covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adj Diff: Day 169 MCS
Estimated Value 3.04
Confidence Interval (2-Sided) 95%
0.91 to 5.17
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in mean changes from baseline between the 2 treatment groups (ABA and PLA) in PCS, MCS, and the 8 subscale scores at Day 85 were compared using ANCOVA models. Adjusted difference (Adj Diff) from PLA group with 95% CIs and p-values were calculated, and adjustment was based on ANCOVA model with treatment group as factor and baseline value as covariate.
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 Adj Diff: Day 169 Physical Function
Estimated Value 4.03
Confidence Interval (2-Sided) 95%
2.08 to 5.98
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo (PLA)
Comments [Not Specified]
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 Adj Diff: Day 169 Role-Physical
Estimated Value 5.22
Confidence Interval (2-Sided) 95%
3.10 to 7.35
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments [Not Specified]
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 Adj Diff: Day 169 Bodily Pain
Estimated Value 6.24
Confidence Interval (2-Sided) 95%
4.37 to 8.11
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in mean changes from baseline between the 2 treatment groups (ABA and PLA) in PCS, MCS, and the 8 subscale scores at Day 85 were compared using ANCOVA models. Adjusted difference (Adj Diff) from PLA group with 95% CIs and p-values were calculated, and adjustment was based on ANCOVA model with treatment group as factor and baseline value as covariate.
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 Adj Diff: Day 169 General Health
Estimated Value 3.27
Confidence Interval (2-Sided) 95%
1.64 to 4.90
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in mean changes from baseline between the 2 treatment groups (ABA and PLA) in PCS, MCS, and the 8 subscale scores at Day 85 were compared using ANCOVA models. Adjusted difference (Adj Diff) from PLA group with 95% CIs and p-values were calculated, and adjustment was based on ANCOVA model with treatment group as factor and baseline value as covariate.
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 Adj Diff: Day 169 Vitality
Estimated Value 4.78
Confidence Interval (2-Sided) 95%
2.76 to 6.79
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in mean changes from baseline between the 2 treatment groups (ABA and PLA) in PCS, MCS, and the 8 subscale scores at Day 85 were compared using ANCOVA models. Adjusted difference (Adj Diff) from PLA group with 95% CIs and p-values were calculated, and adjustment was based on ANCOVA model with treatment group as factor and baseline value as covariate.
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 Adj Diff: Day 169 Social Functioning
Estimated Value 4.92
Confidence Interval (2-Sided) 95%
2.71 to 7.12
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in mean changes from baseline between the 2 treatment groups (ABA and PLA) in PCS, MCS, and the 8 subscale scores at Day 85 were compared using ANCOVA models. Adjusted difference (Adj Diff) from PLA group with 95% CIs and p-values were calculated, and adjustment was based on ANCOVA model with treatment group as factor and baseline value as covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.013
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adj Diff: Day 169 Role Emotional
Estimated Value 3.54
Confidence Interval (2-Sided) 95%
0.74 to 6.33
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Differences in mean changes from baseline between the 2 treatment groups (ABA and PLA) in PCS, MCS, and the 8 subscale scores at Day 85 were compared using ANCOVA models. Adjusted difference (Adj Diff) from PLA group with 95% CIs and p-values were calculated, and adjustment was based on ANCOVA model with treatment group as factor and baseline value as covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adj Diff: Mental Health
Estimated Value 2.70
Confidence Interval (2-Sided) 95%
0.79 to 4.60
Estimation Comments [Not Specified]
33.Secondary Outcome
Title DB; Mean Baseline HAQ-DI and HAQ Component Scores in Participants With Assessments at Day 169
Hide Description The HAQ DI is a self-administered questionnaire composed of 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. 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. HAQ-DI is a weighted sum of the scale scores, with a higher score indicating poorer function. The mean baseline value presented represents a time-matched Day 169 baseline value for only that cohort of participants with assessments available at that visit.
Time Frame BL
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was carried out on the intent-to-treat (ITT) population defined as all randomized subjects who received at least one dose of study medication. Two participants were unevaluable for response due to each missing 2 infusions of study drug. N=Number of Participants Analyzed, n=number of participants at visit
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Deviation)
Unit of Measure: units on a scale
HAQ-DI (n=249, n=130) 1.83  (0.58) 1.82  (0.60)
HAQ dressing and grooming (n=214, n=97) 1.64  (0.75) 1.54  (0.69)
HAQ arising (n=214, n=97) 1.42  (0.72) 1.43  (0.73)
HAQ eating (n=214, n=97) 1.76  (0.83) 1.78  (0.87)
HAQ walking (n=213, n=95) 1.56  (0.70) 1.51  (0.76)
HAQ hygiene (n=213, n=97) 2.14  (0.88) 2.21  (0.87)
HAQ reaching (n=213, n=97) 2.04  (0.79) 1.97  (0.87)
HAQ gripping (n=212, n=97) 1.96  (0.53) 1.93  (0.62)
HAQ activities (n=213, n=97) 2.00  (0.79) 1.95  (0.86)
34.Secondary Outcome
Title DB; Adjusted Mean Change From Baseline to Day 169 in HAQ-DI and HAQ Component Scores in Participants With Assessments at Day 169
Hide Description HAQ DI is a self-administered questionnaire composed of 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. Questions evaluated on a 4-point scale: 0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do. HAQ-DI=weighted sum of the scale scores. Higher score indicates poorer function.Change from BL = Post-BL value – time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at Day 169.
Time Frame BL, Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was carried out on the intent-to-treat (ITT) population defined as all randomized subjects who received at least one dose of study medication. Two participants were unevaluable for response due to each missing 2 infusions of study drug. N=Number of Participants Analyzed, n=number of participants at visit
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Deviation)
Unit of Measure: units on a scale
HAQ-DI (n=249, n=130) -0.45  (0.03) -0.11  (0.04)
HAQ dressing and grooming (n=214, n=97) -0.58  (0.05) -0.26  (0.07)
HAQ arising (n=214, n=97) -0.61  (0.04) -0.29  (0.07)
HAQ eating (n=214, n=97) -0.54  (0.05) -0.07  (0.07)
HAQ walking (n=213, n=95) -0.50  (0.05) -0.24  (0.07)
HAQ hygiene (n=213, n=97) -0.28  (0.05) -0.05  (0.07)
HAQ reaching (n=213, n=97) -0.54  (0.05) -0.11  (0.08)
HAQ gripping (n=212, n=97) -0.47  (0.05) -0.15  (0.07)
HAQ activities (n=213, n=97) -0.48  (0.05) -0.08  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Mean changes from baseline in HAQ disability index were compared between treatment groups using analysis of covariance (ANCOVA) models and 95% confidence intervals were calculated. This analysis was based on the LOCF data set. Similar analyses were also conducted for each of the 8 individual categories: 1) dressing and grooming; 2) arising; 3) eating; 4) walking; 5) hygiene; 6) reach; 7) grip; and 8) common daily activities. Adjusted Mean Change From Baseline = Adj M Chg From BL
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 Adj M Chg from BL: HAQ-DI
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-0.44 to -0.23
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Mean changes from baseline in HAQ disability index were compared between treatment groups using analysis of covariance (ANCOVA) models and 95% confidence intervals were calculated. This analysis was based on the LOCF data set. Similar analyses were also conducted for each of the 8 individual categories: 1) dressing and grooming; 2) arising; 3) eating; 4) walking; 5) hygiene; 6) reach; 7) grip; and 8) common daily activities. Adjusted Mean Change From Baseline= Adj M Chg From BL
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 Adj M Chg from BL: Dressing and Grooming
Estimated Value -0.32
Confidence Interval (2-Sided) 95%
-0.49 to -0.14
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Mean changes from baseline in HAQ disability index were compared between treatment groups using analysis of covariance (ANCOVA) models and 95% confidence intervals were calculated. This analysis was based on the LOCF data set. Similar analyses were also conducted for each of the 8 individual categories: 1) dressing and grooming; 2) arising; 3) eating; 4) walking; 5) hygiene; 6) reach; 7) grip; and 8) common daily activities. Adjusted Mean Change From Baseline= Adj M Chg From BL
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 Adj M Chg from BL: Arising
Estimated Value -0.32
Confidence Interval (2-Sided) 95%
-0.47 to -0.16
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Mean changes from baseline in HAQ disability index were compared between treatment groups using analysis of covariance (ANCOVA) models and 95% confidence intervals were calculated. This analysis was based on the LOCF data set. Similar analyses were also conducted for each of the 8 individual categories: 1) dressing and grooming; 2) arising; 3) eating; 4) walking; 5) hygiene; 6) reach; 7) grip; and 8) common daily activities. Adjusted Mean Change From Baseline = Adj M Chg From BL
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 Adj M Chg from BL: Eating
Estimated Value -0.48
Confidence Interval (2-Sided) 95%
-0.65 to -0.30
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Mean changes from baseline in HAQ disability index were compared between treatment groups using analysis of covariance (ANCOVA) models and 95% confidence intervals were calculated. This analysis was based on the LOCF data set. Similar analyses were also conducted for each of the 8 individual categories: 1) dressing and grooming; 2) arising; 3) eating; 4) walking; 5) hygiene; 6) reach; 7) grip; and 8) common daily activities. Adjusted Mean Change From Baseline= Adj M Chg from BL
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adj M Chg from BL: Walking
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-0.44 to -0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Mean changes from baseline in HAQ disability index were compared between treatment groups using analysis of covariance (ANCOVA) models and 95% confidence intervals were calculated. This analysis was based on the LOCF data set. Similar analyses were also conducted for each of the 8 individual categories: 1) dressing and grooming; 2) arising; 3) eating; 4) walking; 5) hygiene; 6) reach; 7) grip; and 8) common daily activities. Adjusted Mean Change From Baseline= Adj M Chg from BL
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adj M Chg from BL: Hygiene
Estimated Value -0.22
Confidence Interval (2-Sided) 95%
-0.39 to -0.05
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Mean changes from baseline in HAQ disability index were compared between treatment groups using analysis of covariance (ANCOVA) models and 95% confidence intervals were calculated. This analysis was based on the LOCF data set. Similar analyses were also conducted for each of the 8 individual categories: 1) dressing and grooming; 2) arising; 3) eating; 4) walking; 5) hygiene; 6) reach; 7) grip; and 8) common daily activities. Adjusted Mean Change From Baseline= Adj M Chg from BL
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 Adj M Chg from BL: Reaching
Estimated Value -0.43
Confidence Interval (2-Sided) 95%
-0.61 to -0.25
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Mean changes from baseline in HAQ disability index were compared between treatment groups using analysis of covariance (ANCOVA) models and 95% confidence intervals were calculated. This analysis was based on the LOCF data set. Similar analyses were also conducted for each of the 8 individual categories: 1) dressing and grooming; 2) arising; 3) eating; 4) walking; 5) hygiene; 6) reach; 7) grip; and 8) common daily activities. Adjusted Mean Change From Baseline= Adj M Chg from BL
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 Adj M Chg from BL: Gripping
Estimated Value -0.32
Confidence Interval (2-Sided) 95%
-0.49 to -0.15
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Abatacept (ABA), Placebo (PLA)
Comments Mean changes from baseline in HAQ disability index were compared between treatment groups using analysis of covariance (ANCOVA) models and 95% confidence intervals were calculated. This analysis was based on the LOCF data set. Similar analyses were also conducted for each of the 8 individual categories: 1) dressing and grooming; 2) arising; 3) eating; 4) walking; 5) hygiene; 6) reach; 7) grip; and 8) common daily activities. Adjusted Mean Change From Baseline= Adj M Chg from BL
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 Adj M Chg from BL: Activities
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-0.58 to -0.22
Estimation Comments [Not Specified]
35.Secondary Outcome
Title DB; Mean Disease Activity Score (DAS)28 (C-Reactive Protein [CRP]) and Mean Disease Activity Score (Erythrocyte Sedimentation Rate [ESR]) at Day 169
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 levels, 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. The mean BL value presented represents a time-matched Day 169 BL value for only that cohort of participants with assessments available at that visit.
Time Frame BL, Day 169
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Hide Analysis Population Description
Analysis was carried out on the intent-to-treat (ITT) population defined as all randomized subjects who received at least one dose of study medication. Two participants were unevaluable for response due to each missing 2 infusions of study drug. N=Number of Participants Analyzed, n=number of participants at visit
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Baseline DAS28 (CRP); n=251, n=130 6.53  (0.89) 6.51  (0.78)
Day 169 DAS28 (CRP); n=251, n=130 4.70  (1.45) 5.78  (1.33)
Baseline DAS28 (ESR); n=182, n=98 6.88  (0.99) 6.88  (0.92)
Day 169 DAS28 (ESR); n=182, n=98 4.90  (1.55) 6.17  (1.34)
36.Secondary Outcome
Title DB; Adjusted Mean Change From Baseline to Day 169 in DAS28 (CRP) and DAS28 (ESR)
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). Change from BL = Post-BL value – time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at Day 169.
Time Frame BL, Day 169
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Hide Analysis Population Description
Analysis was carried out on the intent-to-treat (ITT) population defined as all randomized subjects who received at least one dose of study medication. Two participants were unevaluable for response due to each missing 2 infusions of study drug. N=Number of Participants Analyzed, n=number of participants at visit
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 133
Mean (Standard Error)
Unit of Measure: Units on a Scale
DAS28 (CRP); n=251, n=130 -1.83  (0.08) -0.74  (0.11)
DAS28 (ESR); n=182, n=98 -1.98  (0.10) -0.71  (0.14)
37.Secondary Outcome
Title DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or 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 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.Related AE/SAE=Certain,Probable,Possible,or Missing relationship to Drug
Time Frame From BL up to database lock for DB period (6/2/2004)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 258 133
Measure Type: Number
Unit of Measure: participants
Deaths 1 0
SAEs 27 15
Related SAEs 7 1
SAEs Leading to Discontinuation 7 2
AEs 205 95
Related AEs 107 39
AEs Leading to Discontinuation 9 4
38.Secondary Outcome
Title DB; Number of Participants 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, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).
Time Frame From BL up to database lock for DB period (6/2/2004)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 258 133
Measure Type: Number
Unit of Measure: participants
Infections 97 43
Neoplasms 7 1
Pre-specified autoimmune disorders 4 0
Acute infusional AEs 13 4
Peri-infusional AEs 40 17
39.Secondary Outcome
Title DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality (MA) Criteria
Hide Description Upper Normal Limit (ULN), Lower Normal Limit (LLN), Baseline (BL). Marked abnormality criteria are: Hemoglobin (HGB): >3 g/dL decrease from BL; Hematocrit: <0.75 * BL; Erythrocytes: <0.75 * BL; Platelets (PLT): <0.67 * LLN/>1.5 * ULN, or if BL < LLN then use 0.5 * BL/<100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL<LLN then use <0.8 * BL/>ULN, or if BL>ULN then use >1.2 * BL/<LLN; neutrophils+bands: <1.0 * 10^3 c/uL; eosinophils: >0.750 * 10^3 c/uL; basophils: > 400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750 * 10^3 c/uL/ >7.50 * 10^3 c/uL.
Time Frame From BL up to database lock for DB period (6/2/2004)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Abatacept (ABA) Placebo (PLA)
Hide Arm/Group Description:
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive abatacept on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Participants weighing < 60 kg received 500 mg, participants weighing 60 kg to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29 and every 28 days thereafter for a total of 7 doses. Each dose was infused intravenously over approximately 30 minutes.
Participants with active RA who met the inclusion/exclusion criteria for this study were randomized to receive placebo on a background of DMARDs. Participants must have been treated with anti-TNF therapy for at least 3 months and designated as anti-TNF therapy failures due to inadequate efficacy. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, and 141.
Overall Number of Participants Analyzed 256 131
Measure Type: Number
Unit of Measure: participants
Low HGB (LLN=11.5 g/dL) 0 1
Low hematocrit (LLN=34%) 0 1
Low erythrocytes (LLN=3.8 x10*6 cells/μL) 0 0
Low PLT (LLN=140*10^9 cells/μL) 1 1
High PLT (ULN=450*10^9 cells/L) 1 0
Low leukocytes (LLN= 3.8*10^3 cells/μL) 2 0
High leukocytes (ULN = 10.6*10^3 cells/μL) 18 14
Low neutrophils+bands(LLN=1.8*10^3 cells/μL) 0 0
Low lymphocytes (LLN= 0.7*10^3 cells/μL) 0 0
High lymphocytes(ULN=4.5*10^3 cells/μL) 0 0
High monocytes (ULN=1*10^3 cells/μL) 0 0
High basophils (ULN= 0.2*10^3 cells/μL) 0 0
High eosinophils (ULN= 7*10^3 cells/μL) 0 0
40.Secondary Outcome
Title DB; Number of Participants With Blood Chemistry Laboratories Meeting MA Criteria
Hide Description Marked abnormality criteria: Alkaline phosphatase (ALP): >2* ULN, or if BL>ULN then use >3* BL; aspartate aminotransferase (AST): >3* ULN, or if BL>ULN then use >4* BL; alanine aminotransferase (ALT): >3* ULN, or if BL>ULN then use >4* BL; G-Glutamyl transferase (GGT): >2* ULN, or if BL>ULN then use >3* BL; Bilirubin: >2* ULN, or if BL>ULN then use >4* BL; blood urea nitrogen (BUN): >2* BL; creatinine: >1.5* BL
Time Frame From BL up to database lock for DB period (6/2/2004)