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A Phase III Study of Abatacept (BMS-188667) in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate

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ClinicalTrials.gov Identifier: NCT00048568
Recruitment Status : Completed
First Posted : November 13, 2002
Results First Posted : December 5, 2011
Last Update Posted : December 5, 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: Methotrexate
Drug: Placebo
Enrollment 1250
Recruitment Details Participants in this evaluation were enrolled 116 sites worldwide: 31 sites in the United States; 32 sites in Europe, 13 sites in Canada; 4 sites in Australia; 7 sites in Argentina; 7 sites in Brazil; 7 sites in Mexico; 3 sites in Peru; 5 sites in South Africa; 3 sites in Taiwan; and 4 sites in Turkey.
Pre-assignment Details Of 1250 participants enrolled, 594 participants were not randomized (519 no longer met study criteria, 37 for unknown reasons, 33 withdrew consent, 3 lost to follow-up, 1 administrative reason by sponsor, and 1 adverse event). Four participants (2 per group) were randomized but never treated; 2 no longer met study criteria and 2 withdrew consent.
Arm/Group Title Abatacept (ABA) + Methotrexate (MTX) DB MTX + Placebo DB ABA + MTX [Open-label (OL)]
Hide Arm/Group Description Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of (10-30 mg/wk), although doses of < 10 mg/wk were acceptable if due to toxicity. Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of (10-30 mg/wk), although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Period Title: Double-Blind Period Days 1 to 169
Started 433 219 0
Completed 401 174 0
Not Completed 32 45 0
Reason Not Completed
Adverse Event             11             3             0
Lack of Efficacy             11             33             0
Lost to Follow-up             1             1             0
Withdrawal by Subject             7             4             0
Unknown Reasons             2             4             0
Period Title: Double-Blind Period Days 170 to 365
Started 401 174 0
Completed 385 162 0
Not Completed 16 12 0
Reason Not Completed
Death             1             1             0
Adverse Event             7             1             0
Lack of Efficacy             2             7             0
Withdrawal by Subject             3             1             0
Poor/Non-Compliance             0             1             0
Pregnancy             2             0             0
No Longer Met Study Criteria             1             1             0
Period Title: Open-Label Period
Started 0 0 539
Completed 0 0 379
Not Completed 0 0 160
Reason Not Completed
Death             0             0             13
Adverse Event             0             0             49
Lack of Efficacy             0             0             32
Withdrawal by Subject             0             0             26
Pregnancy             0             0             5
No Longer Met Study Criteria             0             0             2
Administrative Decision By Sponsor             0             0             1
Unknown Reasons             0             0             25
Lost to Follow-up             0             0             7
Arm/Group Title ABA + MTX DB MTX + Placebo DB Total
Hide Arm/Group Description Abatacept was dosed by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of (10-30 mg/wk), although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of (10-30 mg/wk), although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo was administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Total of all reporting groups
Overall Number of Baseline Participants 433 219 652
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 433 participants 219 participants 652 participants
51.5  (12.9) 50.4  (12.4) 51.1  (12.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 433 participants 219 participants 652 participants
Female
96
  22.2%
40
  18.3%
136
  20.9%
Male
337
  77.8%
179
  81.7%
516
  79.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 433 participants 219 participants 652 participants
American Indian or Alaska Native
3
   0.7%
1
   0.5%
4
   0.6%
Asian
18
   4.2%
10
   4.6%
28
   4.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
10
   2.3%
4
   1.8%
14
   2.1%
White
379
  87.5%
193
  88.1%
572
  87.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
23
   5.3%
11
   5.0%
34
   5.2%
Duration of Rheumatoid Arthritis (RA) Disease   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 433 participants 219 participants 652 participants
<= 2 years 99 45 144
> 2 years to <= 5 years 93 46 139
> 5 years to <=10 years 106 54 160
> 10 years 135 74 209
[1]
Measure Description: Number of participants with RA duration <= 2 years, > 2 years to <= 5 years, > 5 years to <= 10 years, and > 10 years as evaluated at baseline.
1.Primary Outcome
Title Number of American College of Rheumatology 20 (ACR 20) Responders at Day 169
Hide Description ACR 20 response requires a patient 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, patient global assessment of disease, patient 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
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Measure Type: Number
Unit of Measure: Participants
288 85
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX DB, MTX + Placebo DB
Comments The study had a 99% power to detect a difference of 20% in ACR 20 between the 2 groups at the 5% level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference
Estimated Value 28.2
Confidence Interval (2-Sided) 95%
19.8 to 36.7
Estimation Comments Estimated difference between ABA + MTX and MTX + PLA is the estimated difference between ABA+MTX and MTX + PLA in the proportion of participants achieving ACR 20 response.
2.Primary Outcome
Title Number of Participants Achieving Clinically Meaningful Improvement in Health Assessment Questionnaire (HAQ) at Day 365
Hide Description The HAQ-DI includes 20 questions to assess physical function in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and common activities. The domain questions are evaluated on a 4-point scale: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do. HAQ-DI=sum of worst scores in each domain dividied by the number of domains answered. HAQ-DI ranges from 0 to a maximum overall score of 3.0. Clinically meaningful HAQ response was defined as an improvement of at least 0.3 units from baseline in HAQ DI.
Time Frame Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Measure Type: Number
Unit of Measure: Participants
270 84
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX DB, MTX + Placebo DB
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Based on the hierarchical testing procedure for the co-primary measures, the study had 98% power to detect 18% difference in HAQ response rate between the two arms at the 5% level.
Method Chi-squared, Corrected
Comments This model includes treatment as the main factor and baseline value as a covariate.
Method of Estimation Estimation Parameter Estimated Difference
Estimated Value 24.4
Confidence Interval (2-Sided) 95%
15.9 to 32.9
Estimation Comments Estimated difference between ABA + MTX and MTX + PLA is the estimated difference between ABA+MTX and MTX + PLA in the proportion of participants achieving HAQ response at Day 365.
3.Primary Outcome
Title Baseline and Mean Change From Baseline (BL) in Radiographic Erosion Score Results at Day 365
Hide Description To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions. The erosion score range is 0 (no radiographic damage) to 145 (worst possible radiographic damage). Change from baseline = Post-baseline - Baseline value
Time Frame BL (Day 0), Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and treated participants in the DB period with radiographic data available at baseline and Day 365. Due to the compliance issues of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 391 195
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
BL 21.68  (18.07) 21.83  (18.63)
Mean Change From BL 0.63  (1.77) 1.14  (2.81)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX DB, MTX + Placebo DB
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments [Not Specified]
Method Nonparametric ANCOVA
Comments The rank of the change from baseline=dependent variable, treatment=the main factor, rank of baseline value as covariate.
4.Primary Outcome
Title Participants With Deaths, Adverse Events (AEs) and SAEs in the Open-Label (OL) Period
Hide Description AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE was defined as any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame Day 365 to Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period.
Arm/Group Title ABA + MTX OL
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Overall Number of Participants Analyzed 539
Measure Type: Number
Unit of Measure: Participants
Deaths 17
SAEs 215
Related SAEs 60
Discontinuations Due to SAEs 36
AEs 518
Related AEs 323
Discontinued Due to AEs 49
5.Primary Outcome
Title Participants With Hematology Values Meeting the Marked Abnormality Criteria in the OL Period
Hide Description 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 and <100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL<LLN then use <0.8 * BL or >ULN, or if BL>ULN then use >1.2 * BL or <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 Day 365 to Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period.
Arm/Group Title ABA + MTX OL
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Overall Number of Participants Analyzed 536
Measure Type: Number
Unit of Measure: Participants
Low Hemoglobin (LLN 11.5 g/dL) 21
Low Hematocrit (LLN 34%) 20
Low Erythrocytes (LLN 38 x 10^6 c/µL) 15
Low Platelet Count (LLN 140 x 10^3 c/µL) 9
High Platelet Count (ULN 415 x 10^3 c/µL) 4
Low Leukocytes (LLN 4 x 10^3 c/µL) 53
High Leukocytes (ULN 10.5 x 10^3 c/µL) 68
Low Absolute Neutrophils (LLN 1.8 x 10^3 c/µL) 14
Low Absolute Lymphocytes (LLN 0.7 x 10^3 c/µL) 109
High Absolute Lymphocytes (ULN 4.5 x 10^3 c/µL) 4
High Absolute Monocytes (ULN 1.0 x 10^3 c/µL) 9
High Absolute Basophils (ULN 0.2 x 10^3 c/µL) 3
High Absolute Eosinophils (ULN 0.4 x 10^3 c/µL) 49
6.Primary Outcome
Title Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria in the OL Period
Hide Description 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 and <100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL<LLN then use <0.8 * BL or >ULN, or if BL>ULN then use >1.2 * BL or <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 Day 365 to Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period.
Arm/Group Title ABA + MTX OL
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Overall Number of Participants Analyzed 536
Measure Type: Number
Unit of Measure: Participants
High ALP (ULN 150 U/L) 3
High AST (ULN 40 U/L) 14
High ALT (ULN 55 U/L) 20
High GGT (ULN 65 U/L) 36
High Bilirubin (ULN 1.2 mg/dL) 6
High BUN (ULN 26 mg/dL) 40
High Creatinine (ULN 1.5 mg/dL) 92
7.Primary Outcome
Title Participants With Electrolyte Values Meeting the Marked Abnormality Criteria in the OL Period
Hide Description Sodium < 0.9 * LLN or > 1.05 * ULN or if BL < LLN then use < 0.95 * BL or > ULN or if BL > ULN then use >1.05 *BL or < LLN; Potassium: < 0.9 * LLN or > 1.1 * ULN or if BL < LLN then use < 0.9 * BL or > ULN or if BL > ULN then use 1.1 * BL or < LLN; Chloride: < 0.9 * LLN or > 1.1 * ULN or if BL < LLN then use <0.9 * BL or >ULN or if BL > ULN then use > 1.1 * BL or < LLN; Calcium <0.8 * LLN or > 1.2 * ULN or if BL < LLN then use <0.67 * BL or > ULN or if BL > ULN then use > 1.3 * BL or < LLN.
Time Frame Day 365 to Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period.
Arm/Group Title ABA + MTX OL
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Overall Number of Participants Analyzed 536
Measure Type: Number
Unit of Measure: Participants
Low Sodium (LLN 135 mmol/L) 11
High Sodium (ULN 148 mmol/L) 2
Low Potassium (LLN 3.5 mmol/L) 11
High Potassium (ULN 5.5 mmol/L) 32
Low Chloride (LLN 96 mmol/L) 1
High Chloride (ULN 109 mmol/L) 0
Low Calcium (LLN 8.5 mg/dL) 0
High Calcium (ULN 10.6 mg/dL) 1
Low Phosphorous (LLN 2.5 mg/dL) 16
High Phosphorous (ULN 5.6 mg/dL) 8
8.Primary Outcome
Title Participants With Glucose, Protein, Metabolites, and Urinalysis Values Meeting the Marked Abnormality Criteria in the OL Period
Hide Description Glucose: < 65 mg/dL or > 220 mg/dL; Fasting Glucose: <0.8 * LLN or > 1.5 * ULN or if BL < LLN then use < 0.8 * BL or > ULN or if BL > ULN then use 1.1 * BL or < LLN; Total protein: < 0.9 * LLN or 1.1 * ULN or if BL < LLN then use 0.9 * BL or > ULN or if BL > ULN then use 1.1 * BL or < LLN; Albumin: < 0.9 * LLN or if BL < LLN then use 0.75 * BL; Uric acid: > 1.5 * ULN or if BL > ULN then use > 2.0 * BL. All urinalysis abnormalities were defined as: if missing BL then use >= 2 or if value >=4, or if BL = 0 or 0.5 then use >= 2, or if BL = 1.0 then use >= 3, or if BL = 2.0 then use >=4.
Time Frame Day 365 to Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period.
Arm/Group Title ABA + MTX OL
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Overall Number of Participants Analyzed 536
Measure Type: Number
Unit of Measure: Participants
Low Serum Glucose (LLN 64 mg/dL) 120
High Serum Glucose (ULN 140 mg/dL) 36
Low Serum Fasting Glucose (LLN 65 mg/dL) 25
High Serum Fasting Glucose (ULN 109 mg/dL) 22
Low Total Protein (LLN 6 g/dL) 11
High Total Protein (ULN 8.5 g/dL) 6
Low Albumin (LLN 3.5 g/dL) 15
High Uric Acid (ULN 8.7 mg/dL) 4
High Urine Protein (ULN Trace) 39
High Urine Glucose (ULN Trace) 39
High Urine Ketones (ULN Positive) 1
High Urine Blood (ULN >=0) 141
High Urine Leukocyte Esterase (ULN >=0) 35
High Urine White Blood Count (ULN 12 hpf) 232
High Urine Red Blood Count (ULN 8 hpf) 181
9.Primary Outcome
Title Mean BL Immunoglobulins Over Time in the OL Period
Hide Description Mean baseline values are those that are reported for each cohort at each time point on Day 365, Day 729, and Day 1,093.
Time Frame BL (Day 0), Day 365, Day 729, Day 1,093
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period (treatment groups represent treatment received in the double-blind period).
Arm/Group Title ABA + MTX DB Placebo + MTX DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 378 161
Mean (Standard Deviation)
Unit of Measure: mg / mL
Immunoglobulin A (IgA) Day 365 327.0  (135.2) 319.2  (145.1)
Immunoglobulin G (IgG) Day 365 1278  (412.4) 1317  (425.4)
Immunoglobulin M (IgM) Day 365 145.1  (86.72) 154.3  (85.53)
IgA Day 729 328.0  (133.8) 317.0  (145.0)
IgG Day 729 1280  (410.4) 1315  (425.3)
IgM Day 729 146.2  (87.34) 153.1  (85.80)
IgA Day 1,093 321.8  (133.4) 318.5  (145.7)
IgG Day 1,093 1273  (392.3) 1319  (436.8)
IgM Day 1,093 148.6  (91.01) 153.5  (88.82)
10.Primary Outcome
Title Mean Change From BL in Immunoglobulins in the OL Period
Hide Description [Not Specified]
Time Frame BL (Day 0), Day 365, Day 729, Day 1,093
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period (treatment groups represent treatment received in the double-blind period).
Arm/Group Title ABA + MTX DB Placebo + MTX DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 378 161
Mean (Standard Error)
Unit of Measure: mg / mL
IgA Day 365 -47.8  (3.16) -8.30  (6.41)
IgG Day 365 -212  (12.77) -52.7  (18.96)
IgM Day 365 -5.05  (1.98) 6.95  (9.73)
IgA Day 729 -38.6  (4.24) -26.6  (9.95)
IgG Day 729 -215  (14.10) -206  (21.86)
IgM Day 729 8.04  (3.96) 6.49  (5.76)
IgA Day 1,093 -46.8  (4.76) -37.9  (9.66)
IgG Day 1,093 -236  (15.94) -245  (25.44)
IgM Day 1,093 4.38  (3.19) 6.01  (5.01)
11.Primary Outcome
Title Participants With Immunogenicity to Abatacept in the Cumulative DB + OL Period
Hide Description Participants with titers to abatacept in the DB and OL periods. Serum samples from abatacept-treated adult participants with active Rheumatoid Arthritis (RA) were screened for the presence of drug-specific antibodies using two validated direct-format enzyme-linked immunosorbent assays (ELISAs) to determine the presence of antibodies to abatacept and or CTLA4-T.
Time Frame Day 1 to Day 1,821
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with serum samples available for evaluation of titers to abatacept.
Arm/Group Title ABA + MTX Cumulative DB + OL Periods
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the DB and OL periods under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; particiapnts ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and particpants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Overall Number of Participants Analyzed 586
Measure Type: Number
Unit of Measure: Participants
56
12.Primary Outcome
Title Number of Participants Experiencing Clinically Significant Changes in Vital Signs in the OL Period
Hide Description Vital signs included body temperature, heart rate, and seated blood pressure. Clinically significant changes were defined as those that were not within the normal range for the participant.
Time Frame Day 365 to Day 1,821. All changes in participant vital signs were monitored on each day of study drug administration prior to dosing and 60 minutes after dosing.
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Hide Analysis Population Description
All treated participants entering the OL period.
Arm/Group Title ABA + MTX OL
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Overall Number of Participants Analyzed 529
Measure Type: Number
Unit of Measure: Participants
Body Temperature 0
Heart Rate 0
Blood Pressure 0
13.Primary Outcome
Title Number of Participants Experiencing AEs of Special Interest in the OL Period
Hide Description AEs were defined as 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 have been identified to be those which may be associated with the use of immunomodulatory agents or infusion of therapeutic proteins. Acute infusional AEs were defined as those that occurred within 1 hour after the start of the infusion.
Time Frame Day 365 to Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period.
Arm/Group Title ABA + MTX OL
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Overall Number of Participants Analyzed 529
Measure Type: Number
Unit of Measure: Participants
Infections/Infestations 452
Neoplasms 71
Autoimmune Disorders 52
Acute Infusional AEs 30
Peri-Infusional AEs 86
14.Primary Outcome
Title Mean BL Hematocrit in the OL Period
Hide Description Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.
Time Frame Baseline (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period (treatment groups represent treatment received in the double-blind period). N = number of participants analyzed and n = the number of participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 378 161
Mean (Standard Deviation)
Unit of Measure: Percentage of Red Blood Cells
Day 365 (n=365, 157) 38.79  (4.60) 39.38  (4.32)
Day 729 (n=328, 143) 38.72  (4.52) 39.39  (4.19)
Day 1,093 (n=312, 138) 38.69  (4.57) 39.46  (4.33)
Day 1,457 (n=292, 130) 38.59  (4.48) 39.40  (4.27)
Day 1,821 (n=262,124) 38.70  (4.44) 39.48  (4.43)
Day 1,905 (n=134, 68) 38.11  (4.56) 39.83  (3.90)
Day 1,989 (n=121,56) 38.07  (4.78) 39.99  (4.12)
Day 2,073 (n=81,38) 37.11  (3.92) 39.12  (3.45)
Day 2,185 (n=82,37) 37.25  (3.83) 39.02  (3.45)
15.Primary Outcome
Title Mean Change From BL in Participant Hematocrit in the OL Period
Hide Description All changes in participant laboratory parameters were monitored on each day of study drug administration.
Time Frame BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period (treatment groups represent treatment received in the double-blind period).N = number of participants analyzed and n = the number of participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 378 161
Mean (Standard Error)
Unit of Measure: Percentage Blood Volume Occupied by RBCs
Day 365 (n=365, 157) 1.87  (0.21) -0.04  (0.24)
Day 729 (n=328, 143) 2.16  (0.20) 1.36  (0.31)
Day 1,093 (n=312, 138) 1.41  (0.20) 0.56  (0.35)
Day 1,457 (n=292, 130) 1.60  (0.23) 1.01  (0.38)
Day 1,821 (n=262,124) 0.85  (0.25) 0.78  (0.34)
Day 1,905 (n=134, 68) 1.63  (0.34) 0.59  (0.48)
Day 1,989 (n=121,56) 1.42  (0.38) 0.94  (0.49)
Day 2,073 (n=81,38) 1.79  (0.42) 0.20  (0.62)
Day 2,185 (n=82,37) 1.42  (0.37) 0.65  (0.61)
16.Primary Outcome
Title Mean BL Platelet Count in the OL Period
Hide Description Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.
Time Frame BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period (treatment groups represent treatment received in the double-blind period).N = number of participants analyzed and n = the number of participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 378 161
Mean (Standard Deviation)
Unit of Measure: 10^9 c/L
Day 365 (n=365, 157) 352.7  (108.5) 339.2  (97.92)
Day 729 (n=328, 143) 351.8  (110.4) 334.2  (91.41)
Day 1,093 (n=312, 138) 351.7  (107.9) 334.8  (96.35)
Day 1,457 (n=292, 130) 352.7  (106.4) 335.0  (98.59)
Day 1,821 (n=262,124) 351.1  (98.28) 334.2  (97.52)
Day 1,905 (n=134, 68) 365.7  (113.9) 333.7  (89.66)
Day 1,989 (n=121,56) 366.1  (115.3) 326.6  (86.82)
Day 2,073 (n=81,38) 375.2  (118.6) 321.2  (90.51)
Day 2,185 (n=82,37) 380.4  (119.7) 320.3  (91.59)
17.Primary Outcome
Title Mean Change From BL in Participant Platelet Count in the OL Period
Hide Description All changes in participant laboratory parameters were monitored on each day of study drug administration.
Time Frame BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period (treatment groups represent treatment received in the double-blind period). N = number of participants analyzed and n = the number of participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 378 161
Mean (Standard Error)
Unit of Measure: 10^9 c/L
Day 365 (n=365, 157) -66.9  (4.29) -29.9  (5.58)
Day 729 (n=328, 143) -59.5  (4.64) -45.4  (6.64)
Day 1,093 (n=312, 138) -53.5  (5.10) -36.8  (7.21)
Day 1,457 (n=292, 130) -59.0  (5.64) -48.7  (7.40)
Day 1,821 (n=262,124) -68.9  (4.92) -59.2  (7.38)
Day 1,905 (n=134, 68) -55.1  (14.57) -47.5  (10.71)
Day 1,989 (n=121,56) -63.7  (8.33) -50.3  (9.83)
Day 2,073 (n=81,38) -69.6  (10.64) -55.3  (11.68)
Day 2,185 (n=82,37) -80.5  (10.68) -53.9  (10.34)
18.Primary Outcome
Title Mean BL Hemoglobin, Total Protein, and Albumin in the OL Period
Hide Description Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.
Time Frame BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period (treatment groups represent treatment received in the double-blind period). N = number of participants analyzed and n = the number of participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 378 161
Mean (Standard Deviation)
Unit of Measure: g/dL
Hemoglobin Day 365 (n=365, 157) 12.49  (1.57) 12.70  (1.56)
Total Protein Day 365 (n=365, 157) 7.23  (0.52) 7.35  (0.56)
Albumin Day 365 (n=365, 157) 4.03  (0.33) 4.13  (0.30)
Hemoglobin Day 729 (n=328, 143) 12.50  (1.54) 12.72  (1.49)
Total Protein Day 729 (n=328, 143) 7.22  (0.52) 7.34  (0.55)
Albumin Day 729 (n=328, 143) 4.01  (0.33) 4.12  (0.29)
Hemoglobin Day 1,093 (n=312, 138) 12.48  (1.55) 12.75  (1.55)
Total Protein Day 1,093 (n=312, 138) 7.23  (0.51) 7.34  (0.55)
Albumin Day 1,093 (n=312, 138) 4.02  (0.33) 4.11  (0.30)
Hemoglobin Day 1,457 (n=292, 130) 12.46  (1.54) 12.74  (1.50)
Total Protein Day 1,457 (n=292, 130) 7.23  (0.51) 7.35  (0.57)
Albumin Day 1,457 (n=292, 130) 4.02  (0.33) 4.12  (0.30)
Hemoglobin Day 1,821 (n=262,124) 12.49  (1.51) 12.79  (1.57)
Total Protein Day 1,821 (n=262,124) 7.23  (0.49) 7.37  (0.56)
Albumin Day 1,821 (n=262,124) 4.02  (0.33) 4.13  (0.30)
Hemoglobin Day 1,905 (n=134, 68) 12.35  (1.55) 12.88  (1.33)
Total Protein Day 1,905 (n=134, 68) 7.27  (0.52) 7.35  (0.53)
Albumin Day 1,905 (n=134, 68) 4.03  (0.32) 4.13  (0.30)
Hemoglobin Day 1,989 (n=121,56) 12.35  (1.60) 12.98  (1.46)
Total Protein Day 1,989 (n=121,56) 7.25  (0.51) 7.38  (0.55)
Albumin Day 1,989 (n=121,56) 4.03  (0.33) 4.12  (0.30)
Hemoglobin Day 2,073 (n=81,38) 12.21  (1.46) 12.84  (1.18)
Total Protein Day 2,073 (n=81,38) 7.18  (0.47) 7.27  (0.44)
Albumin Day 2,073 (n=81,38) 3.98  (0.33) 4.08  (0.33)
Hemoglobin Day 2,185 (n=82,37) 12.25  (1.44) 12.82  (1.19)
Total Protein Day 2,185 (n=82,37) 7.18  (0.47) 7.28  (0.45)
Albumin Day 2,185 (n=82,37) 3.97  (0.32) 4.08  (0.33)
19.Primary Outcome
Title Mean Change From BL in Hemoglobin, Total Protein, and Albumin in the OL Period
Hide Description All changes in participant laboratory parameters were monitored on each day of study drug administration.
Time Frame BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period (treatment groups represent treatment received in the double-blind period). N = number of participants analyzed and n = the number of participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 378 161
Mean (Standard Error)
Unit of Measure: g/dL
Hemoglobin Day 365 (n=365, 157) 0.62  (0.07) -0.09  (0.08)
Total Protein Day 365 (n=365, 157) -0.26  (0.02) -0.25  (0.04)
Albumin Day 365 (n=365, 157) 0.22  (0.02) 0.02  (0.02)
Hemoglobin Day 729 (n=328, 143) 0.95  (0.07) 0.61  (0.10)
Total Protein Day 729 (n=328, 143) -0.01  (0.03) -0.05  (0.05)
Albumin Day 729 (n=328, 143) 0.31  (0.02) 0.23  (0.03)
Hemoglobin Day 1,093 (n=312, 138) 0.75  (0.07) 0.40  (0.11)
Total Protein Day 1,093 (n=312, 138) -0.16  (0.03) -0.26  (0.04)
Albumin Day 1,093 (n=312, 138) 0.13  (0.02) 0.02  (0.03)
Hemoglobin Day 1,457 (n=292, 130) 0.80  (0.07) 0.52  (0.12)
Total Protein Day 1,457 (n=292, 130) -0.28  (0.03) -0.35  (0.05)
Albumin Day 1,457 (n=292, 130) 0.07  (0.02) -0.02  (0.03)
Hemoglobin Day 1,821 (n=262,124) 0.79  (0.08) 0.70  (0.11)
Total Protein Day 1,821 (n=262,124) -0.27  (0.03) -0.35  (0.05)
Albumin Day 1,821 (n=262,124) 0.06  (0.02) -0.05  (0.03)
Hemoglobin Day 1,905 (n=134, 68) 0.74  (0.12) 0.39  (0.16)
Total Protein Day 1,905 (n=134, 68) -0.32  (0.05) -0.31  (0.07)
Albumin Day 1,905 (n=134, 68) 0.05  (0.03) -0.06  (0.04)
Hemoglobin Day 1,989 (n=121,56) 0.59  (0.13) 0.41  (0.17)
Total Protein Day 1,989 (n=121,56) -0.29  (0.05) -0.33  (0.07)
Albumin Day 1,989 (n=121,56) 0.08  (0.03) 0.01  (0.05)
Hemoglobin Day 2,073 (n=81,38) 0.78  (0.15) 0.23  (0.22)
Total Protein Day 2,073 (n=81,38) -0.21  (0.04) -0.24  (0.09)
Albumin Day 2,073 (n=81,38) 0.22  (0.03) 0.09  (0.06)
Hemoglobin Day 2,185 (n=82,37) 0.69  (0.14) 0.40  (0.21)
Total Protein Day 2,185 (n=82,37) -0.20  (0.04) -0.12  (0.09)
Albumin Day 2,185 (n=82,37) 0.30  (0.03) 0.25  (0.06)
20.Primary Outcome
Title Mean BL White Blood Cells in the OL Period
Hide Description Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.
Time Frame BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period (treatment groups represent treatment received in the double-blind period). N = number of participants analyzed and n = the number of participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 378 161
Mean (Standard Deviation)
Unit of Measure: 10^3 c/uL
White Blood Cells Day 365 (n=365, 157) 8.78  (2.83) 8.81  (3.01)
Absolute Neutrophils Day 365 (n=365, 157) 6.45  (2.63) 6.39  (2.67)
Absolute Eosinophils Day 365 (n=365, 157) 0.18  (0.16) 0.18  (0.12)
Absolute Monocytes Day 365 (n=365, 157) 0.42  (0.25) 0.41  (0.26)
White Blood Cells Day 729 (n=328, 143) 8.89  (2.87) 8.73  (2.96)
Absolute Neutrophils Day 729 (n=328, 143) 6.50  (2.63) 6.35  (2.66)
Absolute Eosinophils Day 729 (n=328, 143) 0.18  (0.16) 0.18  (0.12)
Absolute Monocytes Day 729 (n=328, 143) 0.43  (0.25) 0.40  (0.25)
White Blood Cells Day 1,093 (n=312, 138) 8.81  (2.83) 8.80  (3.08)
Absolute Neutrophils Day 1,093 (n=312, 138) 6.46  (2.63) 6.37  (2.71)
Absolute Eosinophils Day 1,093 (n=312, 138) 0.18  (0.16) 0.18  (0.12)
Absolute Monocytes Day 1,093 (n=312, 138) 0.43  (0.25) 0.41  (0.27)
White Blood Cells Day 1,457 (n=292, 130) 8.80  (2.81) 8.74  (3.10)
Absolute Neutrophils Day 1,457 (n=292, 130) 6.43  (2.59) 6.32  (2.73)
Absolute Eosinophils Day 1,457 (n=292, 130) 0.18  (0.17) 0.18  (0.12)
Absolute Monocytes Day 1,457 (n=292, 130) 0.43  (0.25) 0.40  (0.25)
White Blood Cells Day 1,821 (n=262,124) 8.82  (2.76) 8.70  (3.06)
Absolute Neutrophils Day 1,821 (n=262,124) 6.45  (2.56) 6.35  (2.72)
Absolute Eosinophils Day 1,821 (n=262,124) 0.18  (0.16) 0.18  (0.12)
Absolute Monocytes Day 1,821 (n=262,124) 0.42  (0.24) 0.39  (0.22)
White Blood Cells Day 1,905 (n=134, 68) 9.14  (2.83) 8.80  (2.91)
Absolute Neutrophils Day 1,905 (n=134, 68) 6.78  (2.67) 6.56  (2.68)
Absolute Eosinophils Day 1,905 (n=134, 68) 0.17  (0.16) 0.16  (0.11)
Absolute Monocytes Day 1,905 (n=134, 68) 0.37  (0.21) 0.34  (0.19)
White Blood Cells Day 1,989 (n=121,56) 9.16  (2.87) 8.81  (2.93)
Absolute Neutrophils Day 1,989 (n=121,56) 6.86  (2.77) 6.69  (2.74)
Absolute Eosinophils Day 1,989 (n=121,56) 0.15  (0.14) 0.15  (0.10)
Absolute Monocytes Day 1,989 (n=121,56) 0.35  (0.21) 0.35  (0.18)
White Blood Cells Day 2,073 (n=81,38) 9.64  (3.05) 9.22  (3.12)
Absolute Neutrophils Day 2,073 (n=81,38) 7.25  (2.90) 6.97  (2.99)
Absolute Eosinophils Day 2,073 (n=81,38) 0.12  (0.10) 0.13  (0.09)
Absolute Monocytes Day 2,073 (n=81,38) 0.41  (0.22) 0.38  (0.19)
White Blood Cells Day 2,185 (n=82,37) 9.73  (2.98) 9.22  (3.16)
Absolute Neutrophils Day 2,185 (n=82,37) 7.35  (2.84) 6.93  (3.03)
Absolute Eosinophils Day 2,185 (n=82,37) 0.12  (0.11) 0.13  (0.09)
Absolute Monocytes Day 2,185 (n=82,37) 0.40  (0.22) 0.38  (0.20)
21.Primary Outcome
Title Mean Change From BL in White Blood Cells in the OL Period
Hide Description All changes in participant laboratory parameters were monitored on each day of study drug administration.
Time Frame BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period (treatment groups represent treatment received in the double-blind period). N = number of participants analyzed and n = the number of participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 378 161
Mean (Standard Error)
Unit of Measure: 10^3 c/uL
White Blood Cells Day 365 (n=365, 157) -.10  (0.13) -0.44  (0.17)
Absolute Neutrophils Day 365 (n=365, 157) -1.20  (0.12) -0.43  (0.18)
Absolute Eosinophils Day 365 (n=365, 157) -0.02  (0.01) -0.01  (0.01)
Absolute Monocytes Day 365 (n=365, 157) -0.03  (0.01) -0.03  (0.02)
White Blood Cells Day 729 (n=328, 143) -1.35  (0.15) -1.19  (0.20)
Absolute Neutrophils Day 729 (n=328, 143) -1.50  (0.14) -1.49  (0.19)
Absolute Eosinophils Day 729 (n=328, 143) -0.02  (0.01) -0.04  (0.01)
Absolute Monocytes Day 729 (n=328, 143) -0.06  (0.02) -0.03  (0.02)
White Blood Cells Day 1,093 (n=312, 138) -1.50  (0.16) -1.55  (0.22)
Absolute Neutrophils Day 1,093 (n=312, 138) -1.57  (0.15) -1.66  (0.22)
Absolute Eosinophils Day 1,093 (n=312, 138) -0.01  (0.01) -0.01  (0.01)
Absolute Monocytes Day 1,093 (n=312, 138) -0.07  (0.02) -0.08  (0.02)
White Blood Cells Day 1,457 (n=292, 130) -1.36  (0.16) -1.62  (0.25)
Absolute Neutrophils Day 1,457 (n=292, 130) -1.44  (0.15) -1.68  (0.24)
Absolute Eosinophils Day 1,457 (n=292, 130) -0.00  (0.01) 0.01  (0.02)
Absolute Monocytes Day 1,457 (n=292, 130) -0.06  (0.02) -0.07  (0.02)
White Blood Cells Day 1,821 (n=262,124) -1.56  (0.18) -1.71  (0.24)
Absolute Neutrophils Day 1,821 (n=262,124) -1.72  (0.17) -1.92  (0.23)
Absolute Eosinophils Day 1,821 (n=262,124) -0.00  (0.01) 0.01  (0.02)
Absolute Monocytes Day 1,821 (n=262,124) -0.03  (0.02) -0.04  (0.02)
White Blood Cells Day 1,905 (n=134, 68) -0.82  (0.38) -1.11  (0.32)
Absolute Neutrophils Day 1,905 (n=134, 68) -1.30  (0.31) -1.53  (0.33)
Absolute Eosinophils Day 1,905 (n=134, 68) -0.00  (0.02) -0.02  (0.02)
Absolute Monocytes Day 1,905 (n=134, 68) 0.03  (0.02) 0.05  (0.03)
White Blood Cells Day 1,989 (n=121,56) -1.07  (0.26) -0.97  (0.30)
Absolute Neutrophils Day 1,989 (n=121,56) -.152  (0.26) -1.47  (0.33)
Absolute Eosinophils Day 1,989 (n=121,56) 0.01  (0.02) -0.00  (0.02)
Absolute Monocytes Day 1,989 (n=121,56) 0.03  (0.02) 0.03  (0.03)
White Blood Cells Day 2,073 (n=81,38) -1.00  (0.33) -1.54  (0.44)
Absolute Neutrophils Day 2,073 (n=81,38) -1.57  (0.35) -2.17  (0.47)
Absolute Eosinophils Day 2,073 (n=81,38) 0.02  (0.01) 0.04  (0.02)
Absolute Monocytes Day 2,073 (n=81,38) 0.13  (0.03) 0.11  (0.04)
White Blood Cells Day 2,185 (n=82,37) -1.41  (0.33) -1.96  (0.39)
Absolute Neutrophils Day 2,185 (n=82,37) -1.78  (0.33) -2.39  (0.43)
Absolute Eosinophils Day 2,185 (n=82,37) 0.03  (0.02) -0.01  (0.02)
Absolute Monocytes Day 2,185 (n=82,37) 0.08  (0.04) 0.08  (0.04)
22.Primary Outcome
Title Mean BL Liver Function Parameters in the OL Period
Hide Description Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.
Time Frame BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period (treatment groups represent treatment received in the double-blind period). N = number of participants analyzed and n = the number of participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 378 161
Mean (Standard Deviation)
Unit of Measure: U/L
Alkaline Phosphatase Day 365 (n=365, 157) 99.56  (37.11) 98.73  (41.23)
Alanine Aminotransferase Day 365 (n=365, 157) 22.35  (22.07) 23.40  (27.35)
Aspartate Aminotransferase Day 365 (n=365, 157) 21.53  (12.00) 22.87  (15.14)
G-Glutamyl Transferase Day 365 (n=365, 157) 34.89  (32.59) 30.73  (26.54)
Alkaline Phosphatase Day 729 (n=328, 143) 98.30  (35.22) 99.49  (41.24)
Alanine Aminotransferase Day 729 (n=328, 143) 22.74  (22.91) 23.21  (28.38)
Aspartate Aminotransferase Day 729 (n=328, 143) 21.62  (12.35) 22.87  (15.50)
G-Glutamyl Transferase Day 729 (n=328, 143) 35.37  (33.62) 28.73  (19.92)
Alkaline Phosphatase Day 1,093 (n=312, 138) 99.18  (34.95) 99.43  (40.80)
Alanine Aminotransferase Day 1,093 (n=312, 138) 22.75  (23.38) 23.01  (28.87)
Aspartate Aminotransferase Day 1,093 (n=312, 138) 21.60  (12.55) 22.91  (15.69)
G-Glutamyl Transferase Day 1,093 (n=312, 138) 34.34  (29.93) 28.43  (20.15)
Alkaline Phosphatase Day 1,457 (n=292, 130) 100.8  (36.04) 99.75  (41.90)
Alanine Aminotransferase Day 1,457 (n=292, 130) 23.05  (23.95) 23.43  (29.67)
Aspartate Aminotransferase Day 1,457 (n=292, 130) 21.88  (12.84) 23.29  (16.08)
G-Glutamyl Transferase Day 1,457 (n=292, 130) 35.80  (34.83) 28.34  (20.35)
Alkaline Phosphatase Day 1,821 (n=262,124) 99.80  (34.22) 97.68  (33.66)
Alanine Aminotransferase Day 1,821 (n=262,124) 23.22  (24.74) 23.55  (30.34)
Aspartate Aminotransferase Day 1,821 (n=262,124) 21.63  (12.98) 23.50  (16.37)
G-Glutamyl Transferase Day 1,821 (n=262,124) 35.50  (34.74) 27.76  (19.77)
Alkaline Phosphatase Day 1,905 (n=134, 68) 97.33  (35.95) 92.19  (35.33)
Alanine Aminotransferase Day 1,905 (n=134, 68) 22.57  (22.33) 25.65  (39.19)
Aspartate Aminotransferase Day 1,905 (n=134, 68) 21.43  (12.21) 24.60  (20.64)
G-Glutamyl Transferase Day 1,905 (n=134, 68) 35.08  (31.28) 30.01  (22.38)
Alkaline Phosphatase Day 1,989 (n=121,56) 97.46  (35.63) 95.18  (36.81)
Alanine Aminotransferase Day 1,989 (n=121,56) 23.15  (23.24) 27.80  (42.76)
Aspartate Aminotransferase Day 1,989 (n=121,56) 21.55  (12.72) 25.82  (22.44)
G-Glutamyl Transferase Day 1,989 (n=121,56) 35.27  (32.43) 31.39  (23.44)
Alkaline Phosphatase Day 2,073 (n=81,38) 86.87  (30.05) 78.53  (22.77)
Alanine Aminotransferase Day 2,073 (n=81,38) 22.34  (24.62) 27.50  (50.75)
Aspartate Aminotransferase Day 2,073 (n=81,38) 20.93  (12.70) 25.37  (26.59)
G-Glutamyl Transferase Day 2,073 (n=81,38) 35.62  (37.07) 30.47  (21.40)
Alkaline Phosphatase Day 2,185 (n=82,37) 87.33  (30.52) 78.97  (22.92)
Alanine Aminotransferase Day 2,185 (n=82,37) 22.51  (24.78) 27.82  (51.41)
Alanine Aminotransferase Day 2,185 (n=82,37) 20.80  (12.29) 25.81  (26.81)
G-Glutamyl Transferase Day 2,185 (n=82,37) 36.23  (37.42) 30.46  (21.69)
23.Primary Outcome
Title Mean Change From BL in Liver Function Parameters in the OL Period
Hide Description All changes in participant laboratory parameters were monitored on each day of study drug administration.
Time Frame BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period (treatment groups represent treatment received in the double-blind period). N = number of participants analyzed and n = the number of participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 378 161
Mean (Standard Error)
Unit of Measure: U/L
Alkaline Phosphatase Day 365 (n=365, 157) -7.27  (1.60) -10.8  (2.30)
Alanine Aminotransferase Day 365 (n=365, 157) 1.10  (1.25) -2.64  (2.18)
Aspartate Aminotransferase Day 365 (n=365, 157) 1.50  (0.76) -1.42  (1.20)
G-Glutamyl Transferase Day 365 (n=365, 157) -4.42  (1.48) -2.83  (1.79)
Alkaline Phosphatase Day 729 (n=328, 143) -13.3  (1.70) -18.8  (2.85)
Alanine Aminotransferase Day 729 (n=328, 143) 0.39  (1.39) -1.69  (2.38)
Aspartate Aminotransferase Day 729 (n=328, 143) 1.30  (0.83) 0.47  (1.43)
G-Glutamyl Transferase Day 729 (n=328, 143) -4.96  (1.62) -3.98  (1.68)
Alkaline Phosphatase Day 1,093 (n=312, 138) -10.0  (1.69) -13.0  (2.74)
Alanine Aminotransferase Day 1,093 (n=312, 138) 0.81  (1.40) -0.17  (2.52)
Aspartate Aminotransferase Day 1,093 (n=312, 138) 1.11  (0.85) 0.07  (1.39)
G-Glutamyl Transferase Day 1,093 (n=312, 138) -6.81  (1.55) -4.51  (1.54)
Alkaline Phosphatase Day 1,457 (n=292, 130) -12.4  (1.73) -12.0  (3.02)
Alanine Aminotransferase Day 1,457 (n=292, 130) 1.43  (2.66) -3.11  (2.57)
Aspartate Aminotransferase Day 1,457 (n=292, 130) 1.40  (1.73) -1.82  (1.40)
G-Glutamyl Transferase Day 1,457 (n=292, 130) -5.15  (2.35) -3.66  (1.54)
Alkaline Phosphatase Day 1,821 (n=262,124) -14.6  (1.70) -14.7  (1.99)
Alanine Aminotransferase Day 1,821 (n=262,124) -0.95  (1.49) -0.75  (2.65)
Aspartate Aminotransferase Day 1,821 (n=262,124) 0.14  (0.85) -0.52  (1.52)
G-Glutamyl Transferase Day 1,821 (n=262,124) -5.63  (2.04) -4.65  (1.55)
Alkaline Phosphatase Day 1,905 (n=134, 68) -14.9  (2.82) -10.6  (3.19)
Alanine Aminotransferase Day 1,905 (n=134, 68) -2.35  (2.03) -5.74  (4.66)
Aspartate Aminotransferase Day 1,905 (n=134, 68) -0.49  (1.18) -3.00  (2.46)
G-Glutamyl Transferase Day 1,905 (n=134, 68) -6.76  (3.16) -3.09  (2.91)
Alkaline Phosphatase Day 1,989 (n=121,56) -12.4  (2.80) -13.0  (3.80)
Alanine Aminotransferase Day 1,989 (n=121,56) -1.41  (2.04) -4.98  (5.60)
Aspartate Aminotransferase Day 1,989 (n=121,56) 0.20  (1.24) -1.71  (2.98)
G-Glutamyl Transferase Day 1,989 (n=121,56) -3.66  (3.58) -4.00  (2.95)
Alkaline Phosphatase Day 2,073 (n=81,38) -10.6  (3.40) -4.24  (3.57)
Alanine Aminotransferase Day 2,073 (n=81,38) -0.56  (2.82) -8.08  (7.91)
Aspartate Aminotransferase Day 2,073 (n=81,38) 0.95  (1.68) -2.37  (4.26)
G-Glutamyl Transferase Day 2,073 (n=81,38) -10.2  (4.23) -4.92  (3.49)
Alkaline Phosphatase Day 2,185 (n=82,37) -14.2  (2.79) -7.76  (3.40)
Alanine Aminotransferase Day 2,185 (n=82,37) -2.56  (2.84) -7.43  (8.65)
Alanine Aminotransferase Day 2,185 (n=82,37) 0.60  (1.60) -1.43  (4.64)
G-Glutamyl Transferase Day 2,185 (n=82,37) -13.9  (3.81) -4.51  (2.95)
24.Primary Outcome
Title Mean BL Select Laboratory Parameters in the OL Period
Hide Description Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.
Time Frame BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period (treatment groups represent treatment received in the double-blind period). N = number of participants analyzed and n = the number of participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 378 161
Mean (Standard Deviation)
Unit of Measure: mg/dL
Total Bilirubin Day 365 (n=365, 157) 0.42  (0.18) 0.48  (0.23)
Blood Urea Nitrogen (BUN) Day 365 (n=365, 157) 16.05  (5.19) 15.09  (4.41)
Creatinine Day 365 (n=365, 157) 0.74  (0.17) 0.74  (0.17)
Serum Calcium Day 365 (n=365, 157) 9.26  (0.44) 9.26  (0.50)
Inorganic Phosphorous Day 365 (n=365, 157) 3.48  (0.57) 3.56  (0.54)
Serum Glucose Day 365 (n=365, 157) 96.63  (29.30) 98.78  (58.76)
Uric Acid Day 365 (n=365, 157) 4.80  (1.45) 4.83  (1.50)
Total Bilirubin Day 729 (n=328, 143) 0.42  (0.18) 0.48  (0.23)
BUN Day 729 (n=328, 143) 16.02  (5.23) 15.03  (4.40)
Creatinine Day 729 (n=328, 143) 0.74  (0.18) 0.73  (0.17)
Serum Calcium Day 729 (n=328, 143) 9.26  (0.44) 9.24  (0.50)
Inorganic Phosphorous Day 729 (n=328, 143) 3.50  (0.57) 3.55  (0.50)
Serum Glucose Day 729 (n=328, 143) 97.36  (30.59) 98.56  (60.79)
Uric Acid Day 729 (n=328, 143) 4.79  (1.41) 4.75  (1.34)
Total Bilirubin Day 1,093 (n=312, 138) 0.42  (0.18) 0.48  (0.22)
BUN Day 1,093 (n=312, 138) -0.36  (0.26) 0.00  (0.40)
Creatinine Day 1,093 (n=312, 138) 0.73  (0.17) 0.74  (0.17)
Serum Calcium Day 1,093 (n=312, 138) 0.04  (0.03) 0.02  (0.04)
Inorganic Phosphorous Day 1,093 (n=312, 138) 0.02  (0.04) 0.10  (0.05)
Serum Glucose Day 1,093 (n=312, 138) 96.49  (29.70) 97.65  (61.54)
Uric Acid Day 1,093 (n=312, 138) -0.15  (0.06) -0.32  (0.09)
Total Bilirubin Day 1,457 (n=292, 130) 0.42  (0.18) 0.49  (0.23)
BUN Day 1,457 (n=292, 130) 15.86  (5.28) 15.02  (4.36)
Creatinine Day 1,457 (n=292, 130) 0.73  (0.17) 0.74  (0.18)
Serum Calcium Day 1,457 (n=292, 130) 9.26  (0.45) 9.25  (0.46)
Inorganic Phosphorous Day 1,457 (n=292, 130) 3.49  (0.54) 3.54  (0.50)
Serum Glucose Day 1,457 (n=292, 130) 95.81  (28.90) 95.35  (55.47)
Uric Acid Day 1,457 (n=292, 130) 4.73  (1.40) 4.75  (1.32)
Total Bilirubin Day Day 1,821 (n=262,124) 0.42  (0.18) 0.50  (0.23)
BUN Day 1,821 (n=262,124) 15.93  (5.29) 14.88  (3.96)
Creatinine Day 1,821 (n=262,124) 0.73  (0.16) 0.74  (0.18)
Serum Calcium Day 1,821 (n=262,124) 9.25  (0.45) 9.25  (0.46)
Inorganic Phosphorous Day 1,821 (n=262,124) 3.49  (0.53) 3.54  (0.51)
Serum Glucose Day 1,821 (n=262,124) 96.81  (30.21) 98.59  (64.79)
Uric Acid Day 1,821 (n=262,124) 4.66  (1.29) 4.68  (1.31)
Total Bilirubin Day 1,905 (n=134, 68) 0.43  (0.18) 0.50  (0.25)
BUN Day 1,905 (n=134, 68) 16.15  (5.74) 14.77  (3.78)
Creatinine Day 1,905 (n=134, 68) 0.72  (0.16) 0.75  (0.16)
Serum Calcium Day 1,905 (n=134, 68) 9.30  (0.45) 9.30  (0.40)
Inorganic Phosphorous Day 1,905 (n=134, 68) 3.50  (0.56) 3.44  (0.52)
Serum Glucose Day 1,905 (n=134, 68) 96.82  (31.18) 101.1  (74.67)
Uric Acid Day 1,905 (n=134, 68) 4.70  (1.25) 4.93  (1.30)
Total Bilirubin Day 1,989 (n=121,56) 0.43  (0.18) 0.52  (0.27)
BUN Day 1,989 (n=121,56) 16.26  (5.68) 15.18  (3.88)
Creatinine Day 1,989 (n=121,56) 0.71  (0.14) 0.72  (0.15)
Serum Calcium Day 1,989 (n=121,56) 9.31  (0.44) 9.33  (0.42)
Inorganic Phosphorous Day 1,989 (n=121,56) 3.51  (0.57) 3.45  (0.53)
Serum Glucose Day 1,989 (n=121,56) 98.59  (33.41) 104.80  (81.64)
Uric Acid Day 1,989 (n=121,56) 4.72  (1.25) 4.99  (1.36)
Total Bilirubin Day 2,073 (n=81,38) 0.42  (0.19) 0.52  (0.30)
BUN Day 2,073 (n=81,38) 16.36  (5.83) 15.27  (3.91)
Creatinine Day 2,073 (n=81,38) 0.68  (0.13) 0.69  (0.13)
Serum Calcium Day 2,073 (n=81,38) 9.41  (0.36) 9.48  (0.38)
Inorganic Phosphorous Day 2,073 (n=81,38) 3.61  (0.58) 3.52  (0.60)
Serum Glucose Day 2,073 (n=81,38) 100.4  (31.96) 111.1  (97.97)
Uric Acid Day 2,073 (n=81,38) 4.58  (1.19) 4.60  (1.37)
Total Bilirubin Day 2,185 (n=82,37) 0.42  (0.18) 0.52  (0.30)
BUN Day 2,185 (n=82,37) 16.40  (5.86) 15.22  (3.95)
Creatinine Day 2,185 (n=82,37) 0.68  (0.13) 0.69  (0.13)
Serum Calcium Day 2,185 (n=82,37) 9.43  (0.41) 9.48  (0.38)
Inorganic Phosphorous Day 2,185 (n=82,37) 3.58  (0.58) 3.54  (0.61)
Serum Glucose Day 2,185 (n=82,37) 99.29  (30.71) 111.4  (99.31)
Uric Acid Day 2,185 (n=82,37) 4.61  (1.22) 4.60  (1.39)
25.Primary Outcome
Title Mean Change From BL in Select Laboratory Parameters in the OL Period
Hide Description All changes in participant laboratory parameters were monitored on each day of study drug administration.
Time Frame BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period (treatment groups represent treatment received in the double-blind period). N = number of participants analyzed and n = the number of participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 378 161
Mean (Standard Error)
Unit of Measure: mg/dL
Total Bilirubin Day 365 (n=365, 157) 0.06  (0.01) 0.00  (0.01)
Blood Urea Nitrogen (BUN) Day 365 (n=365, 157) 16.05  (5.19) 15.09  (4.41)
Creatinine Day 365 (n=365, 157) 0.74  (0.17) 0.74  (0.17)
Serum Calcium Day 365 (n=365, 157) 0.25  (0.02) 0.22  (0.04)
Inorganic Phosphorous Day 365 (n=365, 157) -0.02  (0.03) -0.12  (0.04)
Serum Glucose Day 365 (n=365, 157) -1.65  (1.26) -4.06  (4.29)
Uric Acid Day 365 (n=365, 157) 0.04  (0.05) -0.06  (0.07)
Total Bilirubin Day 729 (n=328, 143) 0.09  (0.01) 0.05  (0.02)
BUN Day 729 (n=328, 143) -0.38  (0.31) -0.06  (0.35)
Creatinine Day 729 (n=328, 143) 0.08  (0.01) 0.08  (0.01)
Serum Calcium Day 729 (n=328, 143) 0.14  (0.03) 0.18  (0.05)
Inorganic Phosphorous Day 729 (n=328, 143) -0.06  (0.03) -0.10  (0.05)
Serum Glucose Day 729 (n=328, 143) -1.77  (1.67) -4.74  (5.18)
Uric Acid Day 729 (n=328, 143) 0.11  (0.06) 0.00  (0.09)
Total Bilirubin Day 1,093 (n=312, 138) 0.05  (0.01) 0.01  (0.02)
BUN Day 1,093 (n=312, 138) -0.36  (0.26) 0.00  (0.40)
Creatinine Day 1,093 (n=312, 138) -0.00  (0.01) -0.03  (0.01)
Serum Calcium Day 1,093 (n=312, 138) 0.04  (0.03) 0.02  (0.04)
Inorganic Phosphorous Day 1,093 (n=312, 138) 0.02  (0.04) 0.10  (0.05)
Serum Glucose Day 1,093 (n=312, 138) 0.36  (1.63) -4.95  (4.84)
Uric Acid Day 1,093 (n=312, 138) -0.15  (0.06) -0.32  (0.09)
Total Bilirubin Day 1,457 (n=292, 130) 0.01  (0.01) -0.04  (0.02)
BUN Day 1,457 (n=292, 130) -0.48  (0.27) -0.47  (0.42)
Creatinine Day 1,457 (n=292, 130) 0.02  (0.01) -0.03  (0.01)
Serum Calcium Day 1,457 (n=292, 130) -0.08  (0.03) -0.08  (0.04)
Inorganic Phosphorous Day 1,457 (n=292, 130) -0.00  (0.04) 0.02  (0.05)
Serum Glucose Day 1,457 (n=292, 130) 0.43  (1.53) -0.12  (5.09)
Uric Acid Day 1,457 (n=292, 130) -0.19  (0.06) -0.43  (0.09)
Total Bilirubin Day Day 1,821 (n=262,124) 0.01  (0.01) -0.01  (0.04)
BUN Day 1,821 (n=262,124) -0.54  (0.28) 0.30  (0.44)
Creatinine Day 1,821 (n=262,124) -0.01  (0.01) -0.04  (0.02)
Serum Calcium Day 1,821 (n=262,124) -0.07  (0.03) -0.04  (0.04)
Inorganic Phosphorous Day 1,821 (n=262,124) 0.02  (0.04) 0.01  (0.05)
Serum Glucose Day 1,821 (n=262,124) 3.27  (1.86) -0.02  (5.51)
Uric Acid Day 1,821 (n=262,124) -0.13  (0.06) -0.30  (0.09)
Total Bilirubin Day 1,905 (n=134, 68) 0.01  (0.02) -0.05  (0.04)
BUN Day 1,905 (n=134, 68) -0.36  (0.39) 0.56  (0.57)
Creatinine Day 1,905 (n=134, 68) -0.04  (0.01) -0.03  (0.02)
Serum Calcium Day 1,905 (n=134, 68) -0.12  (0.04) -0.11  (0.05)
Inorganic Phosphorous Day 1,905 (n=134, 68) -0.03  (0.06) 0.11  (0.08)
Serum Glucose Day 1,905 (n=134, 68) 3.00  (2.96) -0.50  (9.71)
Uric Acid Day 1,905 (n=134, 68) -0.29  (0.09) -0.29  (0.12)
Total Bilirubin Day 1,989 (n=121,56) 0.01  (0.02) -0.03  (0.03)
BUN Day 1,989 (n=121,56) -0.31  (0.45) 0.09  (0.64)
Creatinine Day 1,989 (n=121,56) -0.01  (0.01) -0.02  (0.02)
Serum Calcium Day 1,989 (n=121,56) -0.10  (0.04) -0.08  (0.05)
Inorganic Phosphorous Day 1,989 (n=121,56) -0.07  (0.06) 0.08  (0.08)
Serum Glucose Day 1,989 (n=121,56) -1.58  (2.85) -2.70  (11.88)
Uric Acid Day 1,989 (n=121,56) -0.29  (0.09) -0.38  (0.14)
Total Bilirubin Day 2,073 (n=81,38) 0.04  (0.02) -0.100  (0.04)
BUN Day 2,073 (n=81,38) 0.33  (0.47) 0.84  (0.72)
Creatinine Day 2,073 (n=81,38) 0.05  (0.01) 0.04  (0.03)
Serum Calcium Day 2,073 (n=81,38) -0.10  (0.04) -0.20  (0.08)
Inorganic Phosphorous Day 2,073 (n=81,38) -0.11  (0.07) -0.11  (0.12)
Serum Glucose Day 2,073 (n=81,38) -0.74  (3.13) -18.2  (16.92)
Uric Acid Day 2,073 (n=81,38) -0.08  (0.11) -0.15  (0.16)
Total Bilirubin Day 2,185 (n=82,37) 0.05  (0.02) 0.00  (0.04)
BUN Day 2,185 (n=82,37) 0.51  (0.53) 0.18  (0.56)
Creatinine Day 2,185 (n=82,37) 0.03  (0.01) 0.04  (0.02)
Serum Calcium Day 2,185 (n=82,37) -0.27  (0.04) -0.19  (0.07)
Inorganic Phosphorous Day 2,185 (n=82,37) -0.14  (0.07) -0.13  (0.13)
Serum Glucose Day 2,185 (n=82,37) 6.85  (3.81) -8.86  (17.98)
Uric Acid Day 2,185 (n=82,37) -0.12  (0.10) -0.17  (0.14)
26.Primary Outcome
Title Mean BL Serum Electrolytes in the OL Period
Hide Description Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.
Time Frame BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period (treatment groups represent treatment received in the double-blind period). N = number of participants analyzed and n = the number of participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 378 161
Mean (Standard Deviation)
Unit of Measure: mEq/L
Serum Sodium Day 365 (n=365, 157) 139.9  (2.89) 140.7  (3.03)
Serum Potassium Day 365 (n=365, 157) 4.27  (0.37) 4.29  (0.43)
Serum Chloride Day 365 (n=365, 157) 104.1  (3.17) 105.0  (3.63)
Serum Sodium Day 729 (n=328, 143) 139.8  (2.97) 140.7  (3.06)
Serum Potassium Day 729 (n=328, 143) 4.27  (0.36) 4.30  (0.42)
Serum Chloride Day 729 (n=328, 143) 103.9  (3.13) 104.9  (3.65)
Serum Sodium Day 1,093 (n=312, 138) 139.9  (2.88) 140.7  (3.11)
Serum Potassium Day 1,093 (n=312, 138) 4.27  (0.36) 4.27  (0.39)
Serum Chloride Day 1,093 (n=312, 138) 104.0  (3.08) 104.9  (3.64)
Serum Sodium Day 1,457 (n=292, 130) 139.9  (2.83) 140.7  (3.16)
Serum Potassium Day 1,457 (n=292, 130) 4.27  (0.35) 4.27  (0.38)
Serum Chloride Day 1,457 (n=292, 130) 104.0  (3.06) 105.0  (3.64)
Serum Sodium Day 1,821 (n=262,124) 140.0  (2.84) 140.7  (3.11)
Serum Potassium Day 1,821 (n=262,124) 4.26  (0.36) 4.28  (0.40)
Serum Chloride Day 1,821 (n=262,124) 104.1  (3.08) 104.8  (3.60)
Serum Sodium Day 1,905 (n=134, 68) 139.6  (3.13) 140.5  (3.56)
Serum Potassium Day 1,905 (n=134, 68) 4.25  (0.37) 4.25  (0.42)
Serum Chloride Day 1,905 (n=134, 68) 103.9  (3.44) 104.9  (4.03)
Serum Sodium Day 1,989 (n=121,56) 139.5  (3.14) 140.1  (3.72)
Serum Potassium Day 1,989 (n=121,56) 4.27  (0.41) 4.24  (0.43)
Serum Chloride Day 1,989 (n=121,56) 103.8  (3.61) 104.8  (4.33)
Serum Sodium Day 2,073 (n=81,38) 138.2  (2.33) 139.0  (3.91)
Serum Potassium Day 2,073 (n=81,38) 4.31  (0.44) 4.27  (0.48)
Serum Chloride Day 2,073 (n=81,38) 102.3  (2.57) 103.0  (4.23)
Serum Sodium Day 2,185 (n=82,37) 138.2  (2.31) 138.9  (3.93)
Serum Potassium Day 2,185 (n=82,37) 4.30  (0.43) 4.28  (0.49)
Serum Chloride Day 2,185 (n=82,37) 102.3  (2.51) 102.9  (4.24)
27.Primary Outcome
Title Mean Change From BL in Serum Electrolytes in the OL Period
Hide Description All changes in participant laboratory parameters were monitored on each day of study drug administration.
Time Frame BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period (treatment groups represent treatment received in the double-blind period). N = number of participants analyzed and n = the number of participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 378 161
Mean (Standard Error)
Unit of Measure: mEq/L
Serum Sodium Day 365 (n=365, 157) -0.42  (0.17) -1.37  (0.27)
Serum Potassium Day 365 (n=365, 157) -0.01  (0.02) -0.06  (0.03)
Serum Chloride Day 365 (n=365, 157) 0.43  (0.14) -0.21  (0.25)
Serum Sodium Day 729 (n=328, 143) 0.71  (0.19) -0.29  (0.29)
Serum Potassium Day 729 (n=328, 143) -0.03  (0.02) -0.12  (0.04)
Serum Chloride Day 729 (n=328, 143) 0.63  (0.17) 0.15  (0.27)
Serum Sodium Day 1,093 (n=312, 138) -0.29  (0.21) -1.34  (0.34)
Serum Potassium Day 1,093 (n=312, 138) -0.05  (0.02) -0.08  (0.04)
Serum Chloride Day 1,093 (n=312, 138) -0.35  (0.18) -1.17  (0.31)
Serum Sodium Day 1,457 (n=292, 130) -0.18  (0.25) -0.88  (0.40)
Serum Potassium Day 1,457 (n=292, 130) -0.03  (0.03) -0.08  (0.04)
Serum Chloride Day 1,457 (n=292, 130) 104.0  (3.06) 105.0  (3.64)
Serum Sodium Day 1,821 (n=262,124) -0.68  (0.24) -1.29  (0.38)
Serum Potassium Day 1,821 (n=262,124) -0.08  (0.02) -0.15  (0.04)
Serum Chloride Day 1,821 (n=262,124) -0.19  (0.22) -0.69  (0.34)
Serum Sodium Day 1,905 (n=134, 68) -0.27  (0.36) -0.75  (0.54)
Serum Potassium Day 1,905 (n=134, 68) -0.06  (0.04) -0.06  (0.05)
Serum Chloride Day 1,905 (n=134, 68) 0.31  (0.33) -0.15  (0.53)
Serum Sodium Day 1,989 (n=121,56) -0.02  (0.40) -0.25  (0.66)
Serum Potassium Day 1,989 (n=121,56) -0.05  (0.04) -0.12  (0.06)
Serum Chloride Day 1,989 (n=121,56) 0.40  (0.38) -0.52  (0.60)
Serum Sodium Day 2,073 (n=81,38) 2.56  (0.32) 2.05  (0.71)
Serum Potassium Day 2,073 (n=81,38) -0.10  (0.05) -0.14  (0.08)
Serum Chloride Day 2,073 (n=81,38) 2.27  (0.40) 1.89  (0.72)
Serum Sodium Day 2,185 (n=82,37) 2.76  (0.34) 2.24  (0.68)
Serum Potassium Day 2,185 (n=82,37) -0.11  (0.05) -0.20  (0.08)
Serum Chloride Day 2,185 (n=82,37) 2.95  (0.40) 1.81  (0.72)
28.Secondary Outcome
Title Mean Number of Tender Joints and Swollen Joints at DB BL
Hide Description [Not Specified]
Time Frame BL (Day 0)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and treated participants in the DB period.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed by weight with participants weighing < 60 kg received 500 mg, subjects weighing 60 kg to 100 kg received 750 mg, and subjects weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29, and every 28 days thereafter for a total of 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of (10-30 mg/wk), although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of (10-30 mg/wk), although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 433 219
Mean (Standard Deviation)
Unit of Measure: Joints
Tender Joints 31.0  (13.2) 32.3  (13.6)
Swollen Joints 21.4  (8.8) 22.1  (8.8)
29.Secondary Outcome
Title Mean DB BL Participant Physical Pain Assessment, Participant Global Assessment, and Physician Global Assessment
Hide Description Participant physical pain assessment was determined at baseline on the Visual Analog Scale (VAS) of 0 mm to 100 mm where 0mm is no pain and 100mm is worst pain possible. The mean participant global assessment is a measure of overall disease burden and is a component of the ACR and evaluated using the VAS 100 mm. The physician global assessment is a measure of overall disease burden and is a component of the ACR and evaluated using the VAS 0mm to 100 mm with 0mm indicating no disease burden and 100mm indicating worse disease burden possible.
Time Frame BL (Day 0)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and treated participants in the DB period.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed by weight with participants weighing < 60 kg received 500 mg, subjects weighing 60 kg to 100 kg received 750 mg, and subjects weighing > 100 kg received 1 gram. Study medication was administered on Days 1, 15, 29, and every 28 days thereafter for a total of 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of (10-30 mg/wk), although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of (10-30 mg/wk), although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 433 219
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Participant Physical Pain Assessment 63.3  (21.1) 65.9  (20.6)
Participant Global Assessment 62.7  (21.2) 62.8  (21.6)
Physician Global Assessment 68.0  (16.0) 67.4  (17.0)
30.Secondary Outcome
Title BL Rheumatoid Factor (RF) Status for Participants Continuing in the OL Period
Hide Description This analysis determined whether participants in the OL period were RF positive or RF negative based on serum samples. A positive value for RF was > 20 IU/ml; a negative value for RF was ≤ 20 IU/mL.
Time Frame BL (Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in the OL period (treatment groups represent treatment received in the DB period).
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 378 161
Measure Type: Number
Unit of Measure: Participants
RF Negative 42 18
RF Positive 312 130
31.Secondary Outcome
Title ACR 20 Responders at Day 365
Hide Description ACR 20 response requires a patient 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, patient global assessment of disease, patient assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in 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 365
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Measure Type: Number
Unit of Measure: Participants
310 85
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX DB, MTX + Placebo DB
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 Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference
Estimated Value 33.4
Confidence Interval (2-Sided) 95%
25.1 to 41.7
Estimation Comments Estimated difference between ABA + MTX and MTX + PLA is the estimated difference between ABA+MTX and MTX + PLA in the proportion of participants achieving ACR 20 response at Day 365.
32.Secondary Outcome
Title ACR 20 Responders in the Double-Blind (DB) Period
Hide Description ACR 20 response requires a patient 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, patient global assessment of disease, patient assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in HAQ score.
Time Frame Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Measure Type: Number
Unit of Measure: Participants
Day 15 97 30
Day 29 155 51
Day 57 237 75
Day 85 262 80
Day 113 283 86
Day 141 291 93
Day 169 288 85
Day 225 318 91
Day 281 312 94
Day 365 310 85
33.Secondary Outcome
Title ACR 50 Responders at Day 169
Hide Description ACR 50 response requires a patient to have a 50% reduction in the number of swollen and tender joints, and a reduction of 50% in three of the following five parameters: physician global assessment of disease, patient global assessment of disease, patient assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in HAQ score. A participant achieved a sustained ACR 50 response if the participant had ACR 50 observed for at least 2 consecutive study visits.
Time Frame Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Measure Type: Number
Unit of Measure: Participants
169 36
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX DB, MTX + Placebo DB
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 Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference
Estimated Value 23.0
Confidence Interval (2-Sided) 95%
15.0 to 31.1
Estimation Comments Estimated difference between ABA + MTX and MTX + PLA is the estimated difference between ABA+MTX and MTX + PLA in the proportion of participants achieving ACR 50 response at Day 169.
34.Secondary Outcome
Title ACR 50 Responders at Day 365
Hide Description ACR 50 response requires a patient to have a 50% reduction in the number of swollen and tender joints, and a reduction of 50% in three of the following five parameters: physician global assessment of disease, patient global assessment of disease, patient assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in HAQ score.
Time Frame Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Measure Type: Number
Unit of Measure: Participants
205 39
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX DB, MTX + Placebo DB
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 Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference
Estimated Value 30.1
Confidence Interval (2-Sided) 95%
21.8 to 38.5
Estimation Comments Estimated difference between ABA + MTX and MTX + PLA is the estimated difference between ABA+MTX and MTX + PLA in the proportion of participants achieving ACR 50 response at Day 365.
35.Secondary Outcome
Title ACR 50 Responders in the DB Period
Hide Description ACR 50 response requires a patient to have a 50% reduction in the number of swollen and tender joints, and a reduction of 50% in three of the following five parameters: physician global assessment of disease, patient global assessment of disease, patient assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in HAQ score. A participant achieved a sustained ACR 50 response if the participant had ACR 50 observed for at least 2 consecutive study visits.
Time Frame Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Measure Type: Number
Unit of Measure: Participants
Day 15 12 2
Day 29 36 9
Day 57 87 16
Day 85 135 17
Day 113 148 27
Day 141 162 39
Day 169 169 36
Day 225 197 42
Day 281 200 38
Day 365 205 39
36.Secondary Outcome
Title ACR 70 Responders at Day 169
Hide Description ACR 70 response requires a patient to have a 70% reduction in the number of swollen and tender joints, and a reduction of 70% in three of the following five parameters: physician global assessment of disease, patient global assessment of disease, patient assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in HAQ score.
Time Frame Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Measure Type: Number
Unit of Measure: Participants
84 14
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX DB, MTX + Placebo DB
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 Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference
Estimated Value 13.3
Confidence Interval (2-Sided) 95%
7.0 to 19.5
Estimation Comments Estimated difference between ABA + MTX and MTX + PLA is the estimated difference between ABA + MTX and MTX + PLA in the proportion of participants achieving ACR 70 response at Day 169.
37.Secondary Outcome
Title ACR 70 Responders at Day 365
Hide Description ACR 70 response requires a patient to have a 70% reduction in the number of swollen and tender joints, and a reduction of 70% in three of the following five parameters: physician global assessment of disease, patient global assessment of disease, patient assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in HAQ score.
Time Frame Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Measure Type: Number
Unit of Measure: Participants
122 13
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX DB, MTX + Placebo DB
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 Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 22.7
Confidence Interval (2-Sided) 95%
15.6 to 29.8
Estimation Comments [Not Specified]
38.Secondary Outcome
Title ACR 70 Responders in the DB Period
Hide Description ACR 70 response requires a patient to have a 70% reduction in the number of swollen and tender joints, and a reduction of 70% in three of the following five parameters: physician global assessment of disease, patient global assessment of disease, patient assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in HAQ score.
Time Frame Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Measure Type: Number
Unit of Measure: Participants
Day 15 4 1
Day 29 8 2
Day 57 27 6
Day 85 54 7
Day 113 57 12
Day 141 75 12
Day 169 84 14
Day 225 103 16
Day 281 106 19
Day 365 122 13
39.Secondary Outcome
Title Number of Participants Achieving Major Clinical Response By Day 365
Hide Description A Major Clinical Response (MCR) is defined as maintenance of an ACR 70 response over a continuous 6-month period.
Time Frame Day 1 to Day 365. Data were collected monthly during the first 6 months and then every other month (with the exception of Day 337) during the second 6 months of the DB period.
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Measure Type: Number
Unit of Measure: Participants
60 4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX DB, MTX + Placebo DB
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 Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference
Estimated Value 12.3
Confidence Interval (2-Sided) 95%
7.3 to 17.2
Estimation Comments Estimated difference between ABA + MTX and MTX + PLA is the estimated difference between ABA+MTX and MTX + PLA in the proportion of participants achieving MCR.
40.Secondary Outcome
Title Mean BL and Disease Activity Score 28 (DAS-28; Erythrocyte Sedimentation Rate [ESR]) at Day 169 and Day 365
Hide Description The DAS 28 is an assessment of disease activity measured on a visual analog scale (VAS)of 100 mm. The scale reports from 1 to 10, with increasing number indicating increasing extent of disease progression. Scores for disease activity are defined as high (>5.1); low (≤3.2); remission (<2.6). Time-matched BL(Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.
Time Frame BL (Day 0), Day 169, Day 365, Day 169, Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis. Last Observation Carried Forward (LOCF) analysis. N = participants analyzed and n = participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
BL (Day 0) for Day 169 Cohort (n=366, 179) 6.82  (0.87) 6.84  (0.82)
BL (Day 0) for Day 169 Cohort (n=366, 179) 4.34  (1.38) 5.50  (1.35)
BL (Day 0) for Day 365 Cohort (n=375, 183) 6.82  (0.87) 6.83  (0.82)
BL (Day 0) for Day 365 Cohort (n=375, 183) 3.97  (1.40) 5.36  (1.32)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX DB, MTX + Placebo DB
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 Estimated Difference on Day 169
Estimated Value -1.15
Confidence Interval (2-Sided) 95%
-1.38 to -0.91
Estimation Comments Estimated difference between ABA + MTX and MTX + PLA on Day 169.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ABA + MTX DB, MTX + Placebo DB
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 Estimated Difference on Day 365
Estimated Value -1.39
Confidence Interval (2-Sided) 95%
-1.63 to -1.16
Estimation Comments Estimated difference between ABA + MTX and MTX + PLA on Day 365.
41.Secondary Outcome
Title Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, Discontinuation Due to SAEs, AEs, Related AEs, or Discontinued Due to AEs in the DB Period
Hide Description AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE was defined as any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame Day 1 to Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
All treated subjects in the DB period.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 433 219
Measure Type: Number
Unit of Measure: Participants
Deaths 1 1
SAEs 65 26
Related SAEs 15 1
Discontinuations Due to SAEs 10 3
AEs 378 184
Related AEs 214 104
Discontinued Due to AEs 18 4
42.Secondary Outcome
Title Mean DB BL and Mean Change From BL in Joint Space Narrowing (JSN) and Total Score (TS)
Hide Description To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and joint space narrowing (JSN). The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage. Change from baseline = Post-baseline - Baseline value.
Time Frame BL (Day 0), Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and treated participants in the DB period with radiographic data available at baseline and Day 365. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 391 195
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Baseline Mean JSN 22.79  (20.16) 23.02  (20.36)
Mean Change From Baseline JSN Day 365 0.58  (1.54) 1.18  (2.58)
Baseline Mean TS 44.47  (37.33) 44.85  (37.72)
Mean Change From Baseline TS Day 365 1.21  (2.94) 2.32  (5.04)
43.Secondary Outcome
Title Mean DB BL Physical Component Summary of Health-Related Quality of Life (SF-36)
Hide Description The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful. Time-matched BL(Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.
Time Frame BL (Day 0), Day 169, Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population.Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis. Last Observation Carried Forward (LOCF) analysis. N = participants analyzed and n = participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
BL (Day 0) for Day 169 Cohort (n= 416, 207) 30.49  (7.18) 30.61  (7.42)
BL (Day 0) for Day 365 Cohort (n=417, 207) 30.51  (7.17) 30.62  (7.42)
44.Secondary Outcome
Title Adjusted Mean Change From BL in the Physical Component Summary of Health-Related Quality of Life (SF-36) in the DB Period
Hide Description The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.
Time Frame BL (Day 0), Day 169, Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population.Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis. Last Observation Carried Forward (LOCF) analysis. N = participants analyzed and n = participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Mean (Standard Error)
Unit of Measure: Units on a Scale
Day 169 (n=416, 207) 8.82  (0.42) 4.77  (0.59)
Day 365 (n=417, 207) 9.12  (0.43) 4.97  (0.61)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX DB, MTX + Placebo DB
Comments Adjustment based on ANCOVA model with treatment 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 Adjusted Mean Difference at Day 169
Estimated Value 4.06
Confidence Interval (2-Sided) 95%
2.64 to 5.57
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ABA + MTX DB, MTX + Placebo DB
Comments Adjustment based on ANCOVA model with treatment 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 Adjusted Mean Difference at Day 365
Estimated Value 4.15
Confidence Interval (2-Sided) 95%
2.69 to 5.62
Estimation Comments [Not Specified]
45.Secondary Outcome
Title Participants in the DB Period Achieving an Extended Major Clinical Response
Hide Description An extended major clinical response (MCR) was defined as a continuous ACR 70 response over any nine month treatment period with study medications. ACR 70 response criteria requires a patient to have a 70% reduction in the number of swollen and tender joints, and a reduction of 70% in three of the following five parameters: physician global assessment of disease, patient global assessment of disease, patient assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in HAQ score.
Time Frame Day 1 to Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Measure Type: Number
Unit of Measure: Participants
26 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABA + MTX DB, MTX + Placebo DB
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference
Estimated Value 5.7
Confidence Interval (2-Sided) 95%
2.4 to 9.0
Estimation Comments Estimated difference between ABA + MTX and MTX + PLA is the estimated difference between ABA+MTX and MTX + PLA in the proportion of participants achieving extended MCR.
46.Secondary Outcome
Title Mean BL DAS-28 C-Reactive Protein (CRP) and ESR in the DB Period
Hide Description The mean baseline CRP and ESR in the DB period on Day 169 and Day 365 was evaluated for all treated participants. Time-matched BL(Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.
Time Frame BL (Day 0), Day 169, Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population.Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis. Last Observation Carried Forward (LOCF) analysis. N = participants analyzed and n = participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Mean (Standard Deviation)
Unit of Measure: mg / mL
BL (Day 0) CRP for Day 169 Cohort (n=418, 211) 6.37  (0.83) 6.36  (0.82)
BL (Day 0) ESR for Day 169 Cohort (n=418, 211) 6.82  (0.87) 6.84  (0.82)
BL (Day 0) CRP for Day 365 Cohort (n=424, 212) 6.38  (0.83) 6.35  (0.82)
BL (Day 0) ESR for Day 365 Cohort (n=424, 212) 6.82  (0.87) 6.83  (0.82)
47.Secondary Outcome
Title Adjusted Mean Change From BL in DAS-28 CRP and ESR in the DB Period
Hide Description The mean change from baseline in CRP and ESR in the DB period was evaluated for all treated participants. Adjustment based on ANCOVA model with treatment as factor and baseline value as covariate.
Time Frame BL (Day 0), Day 169, Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the closure of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis. N = number of participants analyzed and n = the number of participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Mean (Standard Error)
Unit of Measure: mg / mL
DAS-28 CRP Day 169 (n=418, 211) -2.38  (0.06) -1.29  (0.09)
DAS-28 ESR Day 169 (n=418, 211) -2.48  (0.07) -1.33  (0.10)
DAS-28 CRP Day 365 (n=424, 212) -2.71  (0.06) -1.41  (0.09)
DAS-28 ESR Day 365 (n=424, 212) -2.85  (0.07) -1.46  (0.10)
48.Secondary Outcome
Title Mean BL Soluble Interleukin-2 Receptors (sIL2-r) in the DB Period
Hide Description The mean baseline sIL2-r in the DB period was evaluated from serum samples for all treated participants.
Time Frame BL (Day 0), Day 169, Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
All treated subjects in the DB period. N = number of participants analyzed and n = the number of participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Mean (Standard Deviation)
Unit of Measure: mg / mL
Day 169 (n=370, 171) 1776.0  (946.5) 1603.0  (933.1)
Day 365 (n=235, 106) 1674.0  (835.1) 1601.0  (1076.0)
49.Secondary Outcome
Title Mean Change From BL in Soluble Interleukin-2 Receptors (sIL2-r) in the DB Period
Hide Description The mean change from baseline in sIL2-r in the DB period was evaluated for all treated participants.
Time Frame BL (Day 0), Day 169, Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
All treated subjects in the DB period.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Mean (Standard Error)
Unit of Measure: mg / mL
Day 169 (n=370, 171) -519.00  (23.72) -85.50  (32.78)
Day 365 (n=235, 106) -562.00  (40.82) -290.00  (87.97)
50.Secondary Outcome
Title ACR Core Component: Mean Number of Tender Joints at All Post-BL Visits in the DB Period
Hide Description Time-matched BL(Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.
Time Frame Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis. Last observation carried forward (LOCF) analysis. N = participants analyzed and n = participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Mean (Standard Deviation)
Unit of Measure: Joints
BL (Day 0) for Day 15 Cohort (n=416, 210) 25.19  (14.62) 27.93  (14.27)
BL (Day 0) for Day 29 Cohort (n=419, 211) 21.14  (14.69) 24.11  (14.97)
BL (Day 0) for Day 57 Cohort (n=421, 210) 16.70  (14.06) 21.41  (14.15)
BL (Day 0) for Day 85 Cohort (n=417, 208) 14.84  (13.98) 20.58  (15.61)
BL (Day 0) for Day 113 Cohort (n=415, 210) 13.55  (13.35) 19.83  (15.29)
BL (Day 0) for Day 141 Cohort (n=420, 211) 12.59  (13.39) 19.78  (15.74)
BL (Day 0) for Day 169 Cohort (n=420, 211) 11.69  (12.37) 18.70  (15.42)
BL (Day 0) for Day 225 Cohort (n=419, 212) 10.42  (12.04) 18.22  (15.46)
BL (Day 0) for Day 281Cohort (n=419, 211) 9.92  (11.37) 17.10  (16.04)
BL (Day 0) for Day 365 Cohort (n=424, 212) 9.96  (11.87) 18.31  (15.72)
51.Secondary Outcome
Title ACR Core Component: Mean Number of Swollen Joints at All Post-BL Visits in the DB Period
Hide Description The mean number of swollen joints in the DB period was evaluated based on the swollen joint core component of the ACR scoring system where increasing score indicates increasing level of severity. Time-matched BL(Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.
Time Frame Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis. Last observation carried forward (LOCF) analysis. N = participants analyzed and n = participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Mean (Standard Deviation)
Unit of Measure: joints
BL (Day 0) for Day 15 Cohort (n=416, 210) 16.40  (8.63) 18.49  (9.92)
BL (Day 0) for Day 29 Cohort (n=419, 211) 14.04  (9.26) 16.03  (9.23)
BL (Day 0) for Day 57 Cohort (n=421, 210) 11.02  (8.64) 14.77  (9.85)
BL (Day 0) for Day 85 Cohort (n=417, 208) 9.76  (8.99) 14.56  (10.83)
BL (Day 0) for Day 113 Cohort (n=415, 210) 8.73  (8.64) 13.93  (10.69)
BL (Day 0) for Day 141 Cohort (n=420, 211) 7.84  (8.10) 13.28  (10.70)
BL (Day 0) for Day 169 Cohort (n=420, 211) 7.54  (7.77) 13.14  (11.05)
BL (Day 0) for Day 225 Cohort (n=419, 212) 6.80  (7.57) 12.78  (11.06)
BL (Day 0) for Day 281 Cohort (n=419, 211) 6.50  (7.52) 12.46  (10.98)
BL (Day 0) for Day 365 Cohort (n=424, 212) 6.31  (7.16) 12.69  (10.84)
52.Secondary Outcome
Title ACR Core Component: Mean Participant Pain Assessment at All Post-BL Visits in the DB Period
Hide Description Participant self-reported pain 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.
Time Frame Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis. Last observation carried forward (LOCF) analysis. N = participants analyzed and n = participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Day 15 (n=413, 210) 52.39  (22.85) 60.08  (21.90)
Day 29 (n=418, 211) 47.03  (23.84) 54.69  (23.86)
Day 57 (n=419, 209) 40.34  (24.29) 50.11  (25.16)
Day 85 (n=417, 207) 35.97  (24.01) 48.36  (25.53)
Day 113 (n=418, 210) 34.31  (23.61) 48.60  (26.99)
Day 141 (n=420, 211) 33.93  (25.47) 48.26  (27.19)
Day 169 (n=421, 211) 32.69  (24.32) 49.21  (27.13)
Day 225 (n=418, 211) 31.39  (24.01) 47.20  (26.77)
Day 281 (n=419, 210) 31.06  (24.58) 46.18  (27.23)
Day 365 (n=424, 212) 29.78  (24.20) 48.17  (27.82)
53.Secondary Outcome
Title ACR Core Component: Mean Participant Physical Function Assessment at All Post-BL Visits in the DB Period
Hide Description The HAQ-DI includes 20 questions to assess physical function in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and common activities. The domain questions are evaluated on a 4-point scale: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do. HAQ-DI=sum of worst scores in each domain dividied by the number of domains answered. HAQ-DI ranges from 0 to a maximum overall score of 3.0. Clinically meaningful HAQ response was defined as an improvement of at least 0.3 units from baseline in HAQ DI.
Time Frame Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis. Last observation carried forward (LOCF) analysis. N = participants analyzed and n = participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Day 15 (n=405, 206) 1.51  (0.64) 1.58  (0.56)
Day 29 (n=406, 207) 1.41  (0.64) 1.47  (0.60)
Day 57 (n=412, 205) 1.29  (0.65) 1.42  (0.63)
Day 85 (n=407, 203) 1.18  (0.68) 1.32  (0.65)
Day 113 (n=409, 206) 1.16  (0.67) 1.35  (0.68)
Day 141 (n=411, 207) 1.13  (0.71) 1.35  (0.70)
Day 169 (n=413, 207) 1.11  (0.70) 1.31  (0.69)
Day 225 (n=409, 207) 1.06  (0.70) 1.35  (0.70)
Day 281 (n=408, 207) 1.05  (0.70) 1.31  (0.68)
Day 365 (n=415, 208) 1.04  (0.70) 1.34  (0.70)
54.Secondary Outcome
Title ACR Core Component: Mean Participant Global Assessment at All Post-BL Visits in the DB Period
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.
Time Frame Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis. Last observation carried forward (LOCF) analysis. N = participants analyzed and n = participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Day 15 (n=413, 210) 50.90  (22.42) 56.66  (22.33)
Day 29 (n=418, 211) 45.26  (22.72) 53.11  (22.81)
Day 57 (n=419, 209) 39.78  (23.02) 49.34  (23.98)
Day 85 (n=417, 207) 35.07  (23.37) 46.82  (24.71)
Day 113 (n=418, 210) 33.98  (22.59) 47.26  (25.69)
Day 141 (n=420, 211) 33.52  (24.06) 47.52  (26.57)
Day 169 (n=421, 211) 32.37  (23.26) 47.93  (26.24)
Day 225 (n=418, 210) 30.63  (22.48) 46.06  (26.21)
Day 281 (n=419, 211) 29.98  (23.25) 44.45  (26.13)
Day 365 (n=424, 212) 28.95  (23.60) 45.62  (26.92)
55.Secondary Outcome
Title ACR Core Component: Mean Physician Global Assessment at All Post-BL Visits in the DB Period
Hide Description Physician 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 very good global RA assessment and 100mm representing very poor global RA assessment.
Time Frame Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses of efficacy were based on the intent-to-treat population. Due to the non-compliance of a single site, 9 participants in the abatacept group and 5 in the placebo group were not included in this analysis. Last observation carried forward (LOCF) analysis. N = participants analyzed and n = participants with measurements for that time point.
Arm/Group Title ABA + MTX DB MTX + Placebo DB
Hide Arm/Group Description:
Abatacept was dosed intravenously by weight with 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 14 doses. Each dose was infused intravenously over approximately 30 minutes on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337. Participants also received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity.
Control group receiving MTX treatment in combination with placebo. Participants received MTX at a minimum dose of 10-30 mg/wk, although doses of < 10 mg/wk were acceptable if due to toxicity. Placebo and MTX were administered IV on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, and 337.
Overall Number of Participants Analyzed 424 214