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Trial record 75 of 137 for:    "Connective Tissue Disease" | "Abatacept"

Abatacept With Methotrexate- Phase IIB

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ClinicalTrials.gov Identifier: NCT00162266
Recruitment Status : Completed
First Posted : September 13, 2005
Results First Posted : June 1, 2012
Last Update Posted : June 1, 2012
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: Abatacept (BMS-188667)
Drug: Placebo
Enrollment 524
Recruitment Details  
Pre-assignment Details Of 524 subjects who were enrolled in this study, 185 were not randomized (1 reason unknown; 2 adverse event; 9 withdrawal of consent; 160 failure to meet inclusion and/or exclusion criteria; 1 death; 12 for other reasons).
Arm/Group Title Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX) Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate Double-Blind (DB) Placebo + Methotrexate Open-Label (OL) Abatacept (10 mg / kg)
Hide Arm/Group Description Participants in the DB study received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period. Participants in the DB study received a weight-tiered dose of 2 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period. Participants in the DB study received a placebo that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period. Following a 5-month interim (where the placebo group was split into 2mg/kg abatacept or placebo and participants in 2 original abatacept continued at same dose), participants who enrolled in OL period received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by an intravenous (IV) infusion over approximately 30 minutes. Participants weighing < 60 kg received abatacept 500 mg, participants weighing ≥ 60 kg and ≤ 100 kg received abatacept 750 mg, and participants > 100 kg received abatacept 1 g.
Period Title: Double-Blind Period
Started 115 105 119 0
Completed Day 1 to Day 181 98 80 78 0
Completed 90 74 71 0
Not Completed 25 31 48 0
Reason Not Completed
Adverse Event             5             9             11             0
Death             0             1             0             0
Lost to Follow-up             1             2             0             0
Other Reason             1             0             1             0
Lack of Efficacy             13             17             30             0
Withdrawal by Subject             5             2             6             0
Period Title: Open-Label Period
Started 0 0 0 219
Completed 0 0 0 82
Not Completed 0 0 0 137
Reason Not Completed
Death             0             0             0             7
Adverse Event             0             0             0             46
Lack of Efficacy             0             0             0             26
Lost to Follow-up             0             0             0             3
Withdrawal by Subject             0             0             0             31
Administrative Reason By Sponsor             0             0             0             9
Other Reasons             0             0             0             15
Arm/Group Title Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX) Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate Double-Blind (DB) Placebo + Methotrexate Total
Hide Arm/Group Description Participants in the DB study received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period. Participants in the DB study received a weight-tiered dose of 2 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period. Participants in the DB study received a placebo that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period. Total of all reporting groups
Overall Number of Baseline Participants 115 105 119 339
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 115 participants 105 participants 119 participants 339 participants
55.8  (12.5) 54.4  (11.3) 54.7  (12.0) 55.0  (11.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 105 participants 119 participants 339 participants
Female
86
  74.8%
66
  62.9%
79
  66.4%
231
  68.1%
Male
29
  25.2%
39
  37.1%
40
  33.6%
108
  31.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 115 participants 105 participants 119 participants 339 participants
White 100 91 104 295
Black 6 0 3 9
Other 9 14 12 35
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 115 participants 105 participants 119 participants 339 participants
77.8  (18.6) 78.7  (21.4) 79.9  (17.6) 78.8  (19.2)
Rheumatoid Factor Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 115 participants 105 participants 119 participants 339 participants
Negative 14 15 27 56
Positive 99 90 90 279
[1]
Measure Description: Status was not recorded for 4 participants.
Number of Tender Joints  
Mean (Standard Deviation)
Unit of measure:  Joints
Number Analyzed 115 participants 105 participants 119 participants 339 participants
30.8  (12.2) 28.2  (12.0) 29.2  (13.0) 29.4  (12.4)
Number of Swollen Joints  
Mean (Standard Deviation)
Unit of measure:  Joints
Number Analyzed 115 participants 105 participants 119 participants 339 participants
21.3  (8.4) 20.2  (8.9) 21.8  (8.8) 21.1  (8.7)
C-Reactive Protein (CRP) Serum Level  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 115 participants 105 participants 119 participants 339 participants
2.9  (2.8) 3.2  (2.5) 3.2  (3.2) 3.1  (2.9)
Duration of Participant Rheumatoid Arthritis (RA)  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 115 participants 105 participants 119 participants 339 participants
9.7  (9.8) 9.7  (8.1) 8.9  (8.3) 9.4  (8.8)
1.Primary Outcome
Title Number of Responders to American College of Rheumatology 20% Improvement Criteria (ACR 20) at Day 180 of the Double-Blind (DB) Period
Hide Description ACR 20 response requires a participant to have a 20% reduction in the number of swollen and tender joints, and a reduction of 20% in three of the following five parameters: physician global assessment of disease, participant global assessment of disease, participant assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in Health Assessment Questionnaire 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 180
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population. Participants who discontinued the study due to lack of efficacy (ie, worsening rheumatoid arthritis) were considered ACR 20 nonresponders at all subsequent time points. For all subjects who discontinued for other reasons, their last ACR 20 response was carried forward.
Arm/Group Title DB Abatacept 10 mg/kg + Methotrexate DB Abatacept 2 mg/kg + Methotrexate DB Placebo + Methotrexate
Hide Arm/Group Description:
Participants received a weight-tiered dose of 10 mg/kg of abatacept, administered intravenously(IV) monthly plus methotrexate. Participants were maintained on a stable dose of methotrexate(10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and methotrexate (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a weight-tiered dose of 2 mg/kg of abatacept administered IV monthly plus methotrexate. Participants were maintained on a stable dose of methotrexate (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and methotrexate (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold, or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a placebo that was administered IV monthly plus methotrexate. Participants were maintained on a stable dose of methotrexate (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and methotrexate(maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold, or azathioprine) during Days 181 to 360 of the DB period.
Overall Number of Participants Analyzed 115 105 119
Measure Type: Number
Unit of Measure: Participants
70 44 42
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DB Abatacept 10 mg/kg + Methotrexate, DB Placebo + Methotrexate
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
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 25.6
Confidence Interval (2-Sided) 95%
12.8 to 38.4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DB Abatacept 2 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.31
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 6.6
Confidence Interval (2-Sided) 95%
-6.2 to 19.4
Estimation Comments [Not Specified]
2.Primary Outcome
Title Participants Receiving Concomitant Disease Modifying Rheumatic Drugs and Biologics in Open-Label (OL) Period
Hide Description The number of participants receiving concomitant rheumatoid arthritis treatment with disease modifying rheumatic drugs and/or biologics.
Time Frame Day 360 to Day 3,060
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants.
Arm/Group Title OL Abatacept: Original 10 mg / kg Group OL Abatacept: Original 2 mg / kg Group OL Abatacept: Original Placebo Group
Hide Arm/Group Description:
Participants in the double-blind period received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by IV infusion over approximately 30 minutes. Participants weighing < 60 kg received abatacept 500 mg, participants weighing ≥ 60 kg and ≤ 100 kg received abatacept 750 mg, and participants > 100 kg received abatacept 1 g. Participants in the present study received an open-label weight-tiered dose of abatacept 10 mg/kg.
Participants in the double-blind period received a weight-tiered dose of 2 mg/kg of abatacept that was administered monthly by IV infusion over approximately 30 minutes. Participants in the present study received an open-label weight-tiered dose of abatacept 10 mg/kg.
Participants in the double-blind period received a placebo that was administered monthly by IV infusion over approximately 30 minutes. Participants in the present study received an open-label weight-tiered dose of abatacept 10 mg/kg.
Overall Number of Participants Analyzed 84 68 67
Measure Type: Number
Unit of Measure: Participants
Methotrexate 84 68 67
Corticosteroids (oral and/or injectable) 72 57 56
Nonsteroidal antiinfllammatory drugs 78 63 64
Azanthioprine 1 0 1
Chloroquine 0 1 1
Cyclosporine 2 1 0
Gold Sodium Thiomalate 0 1 0
Hydroxychloroquine 2 3 2
Leflunamide 2 0 1
Sulfasalazine 0 0 1
Adalimumab 0 1 0
Etanercept 0 1 0
Infliximab 2 1 0
3.Primary Outcome
Title Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) in OL Period
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with treatment.SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Related AE/SAE=Certain,Probable,Possible,or Missing relationship to drug.
Time Frame Day 360 to Day 3060
Hide Outcome Measure Data
Hide Analysis Population Description
All treated OL participants.
Arm/Group Title OL Abatacept (10 mg / kg)
Hide Arm/Group Description:
OL participants received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by an intravenous (IV) infusion over approximately 30 minutes. Participants weighing < 60 kg received abatacept 500 mg, participants weighing ≥ 60 kg and ≤ 100 kg received abatacept 750 mg, and participants > 100 kg received abatacept 1 g.
Overall Number of Participants Analyzed 219
Measure Type: Number
Unit of Measure: Participants
AEs 211
Related AEs 144
Discontinued Due to AEs 44
SAEs 117
Related SAEs 37
Discontinued Due to SAEs 33
Deaths 8
4.Primary Outcome
Title Number of Participants With AEs of Special Interest in 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 were 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. Peri-Infusional AEs were defined as those that occurred within 24 hours after the start of the infusion.
Time Frame Day 360 to Day 3060
Hide Outcome Measure Data
Hide Analysis Population Description
All treated OL participants.
Arm/Group Title OL Abatacept (10 mg / kg)
Hide Arm/Group Description:
OL participants received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by an intravenous (IV) infusion over approximately 30 minutes. Participants weighing < 60 kg received abatacept 500 mg, participants weighing ≥ 60 kg and ≤ 100 kg received abatacept 750 mg, and participants > 100 kg received abatacept 1 g.
Overall Number of Participants Analyzed 219
Measure Type: Number
Unit of Measure: Participants
Infections/Infestations 179
Malignant Neoplasms 20
Autoimmune Disorders 20
Acute Infusional AEs 20
Peri-Infusional AEs 47
5.Primary Outcome
Title Baseline Serum Immunoglobulin A (IgA) Over Time in OL Period
Hide Description Time-matched baseline (Day 0) values and post-baseline values were presented for each post-baseline visit and represent only that cohort of participants with measurements available at that post-baseline assessment. Mean Change from Baseline data for these cohorts are presented in Outcome Measure 6.
Time Frame Baseline (Day 0) and Days 360, 720,1080, 1440, and 1800
Hide Outcome Measure Data
Hide Analysis Population Description
All treated OL participants. Participants were grouped according to the treatment they received in DB study. n=the number of participants with measurements for that time point.
Arm/Group Title OL Abatacept: Original 10 mg / kg Group OL Abatacept: Original 2 mg / kg Group OL Abatacept: Original Placebo Group
Hide Arm/Group Description:
Participants in the double-blind period received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by IV infusion over approximately 30 minutes. Participants weighing < 60 kg received abatacept 500 mg, participants weighing ≥ 60 kg and ≤ 100 kg received abatacept 750 mg, and participants > 100 kg received abatacept 1 g. Participants in the present study received an open-label weight-tiered dose of abatacept 10 mg/kg.
Participants in the double-blind period received a weight-tiered dose of 2 mg/kg of abatacept that was administered monthly by IV infusion over approximately 30 minutes. Participants in the present study received an open-label weight-tiered dose of abatacept 10 mg/kg.
Participants in the double-blind period received a placebo that was administered monthly by IV infusion over approximately 30 minutes. Participants in the present study received an open-label weight-tiered dose of abatacept 10 mg/kg.
Overall Number of Participants Analyzed 84 68 67
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline for Day 360 cohort (n=74, 59, 60) 308.09  (152.27) 341.54  (148.48) 264.22  (133.90)
Baseline for Day 720 cohort (n=71, 53, 53) 290.25  (146.27) 338.58  (151.76) 256.64  (132.78)
Baseline for Day 1080 cohort (n=59, 45, 45) 287.27  (140.22) 321.02  (153.81) 266.89  (143.48)
Baseline for Day 1440 cohort (n=54, 37, 37) 287.09  (136.50) 327.27  (162.13) 250.11  (127.88)
Baseline for Day 1800 cohort (n=50, 38, 34) 292.78  (146.91) 327.34  (163.27) 244.71  (118.03)
6.Primary Outcome
Title Mean Change From Baseline (BL) in IgA Over Time in OL Period
Hide Description Blood samples for immunoglobulin assessments were obtained to determine change from baseline in serum IgA. Baseline data for these time-matched cohorts are presented in Outcome Measure 5.
Time Frame Baseline (Day 0) and Days 360, 720, 1080, 1440, and 1800
Hide Outcome Measure Data
Hide Analysis Population Description
All treated OL participants. Participants were grouped according to the treatment they received in the DB study. n=the number of participants with measurements for that time point.
Arm/Group Title OL Abatacept: Original 10 mg / kg Group OL Abatacept: Original 2 mg / kg Group OL Abatacept: Original Placebo Group
Hide Arm/Group Description:
Participants in the double-blind period received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by IV infusion over approximately 30 minutes. Participants weighing < 60 kg received abatacept 500 mg, participants weighing ≥ 60 kg and ≤ 100 kg received abatacept 750 mg, and participants > 100 kg received abatacept 1 g. Participants in the present study received an open-label weight-tiered dose of abatacept 10 mg/kg.
Participants in the double-blind period received a weight-tiered dose of 2 mg/kg of abatacept that was administered monthly by IV infusion over approximately 30 minutes. Participants in the present study received an open-label weight-tiered dose of abatacept 10 mg/kg.
Participants in the double-blind period received a placebo that was administered monthly by IV infusion over approximately 30 minutes. Participants in the present study received an open-label weight-tiered dose of abatacept 10 mg/kg.
Overall Number of Participants Analyzed 84 68 67
Mean (Standard Error)
Unit of Measure: mg/dL
Change from BL at Day 360 (n=74, 59, 60) -38.24  (5.95) -25.66  (7.83) 5.00  (6.72)
Change from BL at Day 720 (n=71, 53, 53) -28.20  (8.61) -45.06  (9.27) -20.89  (7.73)
Change from BL at Day 1080 (n=59, 45, 45) -33.10  (13.08) -52.87  (12.86) -15.87  (11.18)
Change from BL at Day 1440 (n=54, 37, 37) -30.52  (9.75) -52.49  (16.32) -4.41  (12.28)
Change from BL at Day 1800 (n=50, 38, 34) -20.06  (26.97) -65.95  (16.26) -25.68  (12.18)
7.Primary Outcome
Title Baseline Immunoglobulin G (IgG) Over Time in OL Period
Hide Description Time-matched baseline (Day 0) values and post-baseline vales were presented for each post-baseline visit and represent only that cohort of participants with measurements available at that post-baseline assessment. Mean Change from Baseline data for these cohorts are presented in Outcome Measure 8.
Time Frame Baseline (Day 0) and Days 360, 720, 1080, 1440 and 1800
Hide Outcome Measure Data
Hide Analysis Population Description
All treated OL participants. Participants were grouped according to the treatment they received in the DB study. n=the number of participants with measurements for that time point.
Arm/Group Title OL Abatacept: Original 10 mg / kg Group OL Abatacept: Original 2 mg / kg Group OL Abatacept: Original Placebo Group
Hide Arm/Group Description:
Participants in the DB period received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by IV infusion over approximately 30 minutes. Participants weighing < 60 kg received abatacept 500 mg, participants weighing ≥ 60 kg and ≤ 100 kg received abatacept 750 mg, and participants > 100 kg received abatacept 1 g. Participants in the present study received an OL weight-tiered dose of abatacept 10 mg/kg.
Participants in the DB period received a weight-tiered dose of 2 mg/kg of abatacept that was administered monthly by IV infusion over approximately 30 minutes. Participants in the present study received an OL weight-tiered dose of abatacept 10 mg/kg.
Participants in the double-blind period received a placebo that was administered monthly by IV infusion over approximately 30 minutes. Participants in the present study received an open-label weight-tiered dose of abatacept 10 mg/kg.
Overall Number of Participants Analyzed 84 68 67
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline for Day 360 cohort (n=75, 59, 60) 1130.31  (295.28) 1086.05  (263.41) 1079.00  (345.72)
Baseline for Day 720 cohort (n=72, 53, 53) 1138.58  (303.24) 1093.23  (318.24) 1076.40  (333.08)
Baseline for Day 1080 cohort (n=60, 45, 45) 1145.15  (305.51) 1053.91  (264.53) 1136.27  (372.58)
Baseline for Day 1440 cohort (n=55, 37, 37) 1154.58  (315.00) 1095.49  (261.86) 1135.43  (381.72)
Baseline for Day 1800 cohort (n=51, 38, 34) 1152.63  (305.01) 1092.76  (260.85) 1137.21  (368.39)
8.Primary Outcome
Title Mean Change From Baseline (BL) in IgG Over Time in OL Period
Hide Description Blood samples for immunoglobulin assessments were obtained to determine change from baseline in serum IgG. Baseline data for these cohorts are presented in Outcome Measure 7.
Time Frame Baseline (Day 0) and Days 360, 720, 1080, 1440, and 1800
Hide Outcome Measure Data
Hide Analysis Population Description
All treated OL participants. Participants were grouped according to the treatment they received in the DB study. n=the number of participants with measurements for that time point.
Arm/Group Title OL Abatacept: Original 10 mg / kg Group OL Abatacept: Original 2 mg / kg Group OL Abatacept: Original Placebo Group
Hide Arm/Group Description:
Participants in the DB period received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by IV infusion over approximately 30 minutes. Participants weighing < 60 kg received abatacept 500 mg, participants weighing ≥ 60 kg and ≤ 100 kg received abatacept 750 mg, and participants > 100 kg received abatacept 1 g. Participants in the present study received an OL weight-tiered dose of abatacept 10 mg/kg.
Participants in the DB period received a weight-tiered dose of 2 mg/kg of abatacept that was administered monthly by IV infusion over approximately 30 minutes. Participants in the present study received an OL weight-tiered dose of abatacept 10 mg/kg.
Participants in the DB period received a placebo that was administered monthly by IV infusion over approximately 30 minutes. Participants in the present study received an OL weight-tiered dose of abatacept 10 mg/kg.
Overall Number of Participants Analyzed 84 68 67
Mean (Standard Error)
Unit of Measure: mg/dL
Change from BL at Day 360 (n=75, 59, 60) -181.92  (19.78) -110.71  (21.46) -15.12  (21.71)
Change from BL at Day 720 (n=72, 53, 53) -183.04  (28.58) -168.55  (31.82) -137.06  (31.62)
Change from BL at Day 1080 (n=60, 45, 45) -199.58  (33.68) -229.91  (26.75) -150.40  (33.97)
Change from BL at Day 1440 (n=55, 37, 37) -228.11  (28.90) -279.14  (33.43) -147.46  (45.84)
Change from BL at Day 1800 (n=51, 38, 34) -217.43  (39.52) -206.21  (39.10) -187.94  (44.40)
9.Primary Outcome
Title Baseline Immunoglobulin M (IgM) Over Time in OL Period
Hide Description Time-matched baseline (Day 0) values and post-baseline values were presented for each post-baseline visit and represent only that cohort of participants with measurements available at that post-baseline assessment. Mean Change from Baseline data for these cohorts are presented in Outcome Measure 10.
Time Frame Baseline (Day 0) and Days 360, 720,1080,1440, and 1800
Hide Outcome Measure Data
Hide Analysis Population Description
All treated OL participants. Participants were grouped according to the treatment they received in the DB study. n=the number of participants with measurements for that time point.
Arm/Group Title OL Abatacept: Original 10 mg / kg Group OL Abatacept: Original 2 mg / kg Group OL Abatacept: Original Placebo Group
Hide Arm/Group Description:
Participants in the DB period received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by IV infusion over approximately 30 minutes. Participants weighing < 60 kg received abatacept 500 mg, participants weighing ≥ 60 kg and ≤ 100 kg received abatacept 750 mg, and participants > 100 kg received abatacept 1 g. Participants in the present study received an OL weight-tiered dose of abatacept 10 mg/kg.
Participants in the DB period received a weight-tiered dose of 2 mg/kg of abatacept that was administered monthly by IV infusion over approximately 30 minutes. Participants in the present study received an OL weight-tiered dose of abatacept 10 mg/kg.
Participants in the DB period received a placebo that was administered monthly by IV infusion over approximately 30 minutes. Participants in the present study received an OL weight-tiered dose of abatacept 10 mg/kg.
Overall Number of Participants Analyzed 84 68 67
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline for Day 360 cohort (n=74, 59, 60) 147.76  (76.05) 134.29  (66.81) 125.10  (52.12)
Baseline for Day 720 cohort (n=71, 53, 53) 147.76  (76.31) 137.79  (69.93) 123.25  (52.79)
Baseline for Day 1080 cohort (n=59, 45, 45) 144.75  (78.89) 127.36  (68.06) 129.04  (54.79)
Baseline for Day 1440 cohort (n=54, 37, 37) 141.69  (77.90) 136.22  (70.90) 133.51  (58.04)
Baseline for Day 1800 cohort (n=45, 33, 32) 133.22  (61.79) 124.15  (67.07) 124.63  (58.69)
10.Primary Outcome
Title Mean Change From Baseline (BL) in IgM in OL Period
Hide Description Blood samples for immunoglobulin assessments were obtained to determine change from baseline in serum IgM. Baseline data for these time-matched cohorts are presented in Outcome Measure 9.
Time Frame Baseline (Day 0) and Days 360, 720, 1080, 1440, and 1800
Hide Outcome Measure Data
Hide Analysis Population Description
All treated OL participants. Participants were grouped according to the treatment they received in the double-blind (DB) study. n = the number of participants with measurements for that time point.
Arm/Group Title OL Abatacept: Original 10 mg/kg Group OL Abatacept: Original 2 mg/kg Group OL Abatacept: Original Placebo Group
Hide Arm/Group Description:
Participants in the DB period received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by intravenous IV infusion over approximately 30 minutes. Participants weighing < 60 kg received abatacept 500 mg, participants weighing ≥ 60 kg and ≤ 100 kg received abatacept 750 mg, and participants > 100 kg received abatacept 1 g. Participants in the present study received an OL weight-tiered dose of abatacept 10 mg/kg.
Participants in the DB period received a weight-tiered dose of 2 mg/kg of abatacept that was administered monthly by IV infusion over approximately 30 minutes. Participants in the present study received an OL weight-tiered dose of abatacept 10 mg/kg.
Participants in the DB period received a placebo that was administered monthly by IV infusion over approximately 30 minutes. Participants in the present study received an OL weight-tiered dose of abatacept 10 mg/kg.
Overall Number of Participants Analyzed 84 68 67
Mean (Standard Error)
Unit of Measure: mg/dL
Change from BL at Day 360 (n=74, 59, 60) -5.81  (3.49) 3.22  (4.36) 11.17  (3.89)
Change from BL at Day 720 (n=71, 53, 53) 12.68  (7.32) 0.11  (4.76) 6.45  (6.11)
Change from BL at Day 1080 (n=59, 45, 45) 0.37  (6.69) 1.93  (6.61) 27.93  (11.62)
Change from BL at Day 1440 (n=54, 37, 37) 2.52  (7.07) 0.68  (8.99) 14.46  (9.52)
Change from BL at Day 1,800 (n=45, 33, 32) 7.84  (6.89) 9.06  (7.55) 6.72  (8.80)
11.Primary Outcome
Title Number of Participants With Hematology Values Meeting Marked Abnormality Criteria in OL Period
Hide Description [Not Specified]
Time Frame Day 360 to Day 3060
Hide Outcome Measure Data
Hide Analysis Population Description
All treated OL participants.
Arm/Group Title OL Abatacept (10 mg / kg)
Hide Arm/Group Description:
OL participants received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by IV infusion over approximately 30 minutes. Participants weighing < 60 kg received abatacept 500 mg, participants weighing ≥ 60 kg and ≤ 100 kg received abatacept 750 mg, and participants > 100 kg received abatacept 1 g.
Overall Number of Participants Analyzed 217
Measure Type: Number
Unit of Measure: Participants
Low Hemoglobin (> 13.0 grams/dL; n=216) 21
Low Hematocrit (< 35%; n=216) 11
Low Platelet Count (<145*10^9 cells/L; n=214) 1
High Platelet Count (>400*10^9 cells/L; n=214) 1
Low Leukocytes (<3.60 *10^3 cells/µL; n=216) 12
High Leukocytes (>10.30*10^3 cells/µL; n=216) 49
Low Neutrophils + Bands (<2.0*10^3 c/uL; n=217) 1
Low Absolute Lymphocytes(<1.0*10^3cells/µL; n=217) 48
High Absolute Lymphocytes(>3.5*10^3cells/µL;n=217) 0
High Absolute Monocytes (>720*10^3cells/µL; n=217) 0
High Absolute Basophils(>0.2*10^3 cells/µL; n=217) 1
High Absolute Eosinophils(>0.4*10^3cells/µL;n=217) 21
12.Primary Outcome
Title Number of Participants With Liver and Kidney Function Values Meeting Marked Abnormality Criteria in OL Period
Hide Description [Not Specified]
Time Frame Day 360 to Day 3060
Hide Outcome Measure Data
Hide Analysis Population Description
All treated OL participants.
Arm/Group Title OL Abatacept (10 mg / kg)
Hide Arm/Group Description:
OL participants received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by an intravenous (IV) infusion over approximately 30 minutes. Participants weighing < 60 kg received abatacept 500 mg, participants weighing ≥ 60 kg and ≤ 100 kg received abatacept 750 mg, and participants > 100 kg received abatacept 1 g.
Overall Number of Participants Analyzed 217
Measure Type: Number
Unit of Measure: Participants
High Alkaline Phosphatase (>117 IU/L) 1
High Aspartate Aminotransferase (>38 IU/L) 6
High Alanine Aminotransferase (>30 IU/L) 5
High G-Glutamyl Transferase (>61 IU/L) 20
High Total Bilirubin (>1.1 mg/dL) 0
High Blood Urea Nitrogen (>21.3 mg/dL) 14
High Creatinine (>1.30 mg/dL) 13
13.Primary Outcome
Title Number of Participants With Electrolyte Values Meeting Marked Abnormality Criteria in OL Period
Hide Description [Not Specified]
Time Frame Day 360 to Day 3060
Hide Outcome Measure Data
Hide Analysis Population Description
All treated OL participants.
Arm/Group Title OL Abatacept (10 mg / kg)
Hide Arm/Group Description:
OL participants received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by IV infusion over approximately 30 minutes. Participants weighing <60 kg received abatacept 500 mg, participants weighing ≥60 kg and ≤100 kg received abatacept 750 mg, and participants >100 kg received abatacept 1 g.
Overall Number of Participants Analyzed 217
Measure Type: Number
Unit of Measure: Participants
Low Serum Sodium (<135 mEq/L; n=217) 4
High Serum Sodium (>145 mEq/L; n=217) 10
Low Serum Potassium (<3.5 mEq/L; n=217) 8
High Serum Potassium (>5.0 mEq/L; n=217) 10
Low Serum Chloride (<97 mEq/L; n=217) 8
High Serum Chloride (>106 mEq/L; n=217) 3
Low Total Calcium (<8.6 mg/dL; n=217) 0
High Total Calcium (>10.2 mg/dL; n=217) 3
Low Inorganic Phosphorus (<2.7 mg/dL; n=217) 5
High Inorganic Phosphorus (> 4.5 mg/dL; n=217) 11
14.Primary Outcome
Title Number of Participants With Glucose, Protein, Metabolites, and Urinalysis Values Meeting Marked Abnormality Criteria in OL Period
Hide Description [Not Specified]
Time Frame Day 360 to Day 3060
Hide Outcome Measure Data
Hide Analysis Population Description
All treated OL participants.
Arm/Group Title OL Abatacept (10 mg / kg)
Hide Arm/Group Description:
OL participants received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by I) infusion over approximately 30 minutes. Participants weighing <60 kg received abatacept 500 mg, participants weighing ≥60 kg and ≤100 kg received abatacept 750 mg, and participants >100 kg received abatacept 1 g.
Overall Number of Participants Analyzed 217
Measure Type: Number
Unit of Measure: Participants
Low Serum Glucose (< 70 mg/dL; n=217) 33
High Serum Glucose (> 110 mg/dL; n=217) 30
Low Fasting Serum Glucose (< 70 mg/dL; n=1) 0
High Fasting Serum Glucose (> 110 mg/dL; n=1) 0
Low Total Protein (< 6.2 grams/dL; n=217) 12
High Total Protein (>8.3 grams/dL; n=217) 1
Low Albumin (<3.5 grams/dL; n=217) 7
High Uric Acid (>7.6 mg/dL; n=217) 2
High Urine Protein (> trace; n=217) 29
High Urine Glucose (> trace; n=217) 32
High Urine Blood (> trace; n=217) 47
High Urine White Blood Cell Count (> trace; n=162) 74
High Urine Red Blood Cell Count (> trace; n=162) 51
15.Secondary Outcome
Title Number of ACR 20 Responders in DB Period
Hide Description ACR 20 response requires a participant to have a 20% reduction in the number of swollen and tender joints, and a reduction of 20% in three of the following five parameters: physician global assessment of disease, participant global assessment of disease, participant assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in 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 Days 15, 30, 60, 90, 120, 150,180, 240, 300, and 360
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 infusion of study medication
Arm/Group Title DB Abatacept 10 mg/kg + Methotrexate DB Abatacept 2 mg/kg + Methotrexate DB Placebo + Methotrexate
Hide Arm/Group Description:
Participants in the DB study received a weight-tiered dose of 10 mg/kg of abatacept administered monthly IV plus methotrexateParticipants were maintained on a stable dose of methotrexate (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and methotrexate (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a weight-tiered dose of 2 mg/kg of abatacept administered monthly IV plus methotrexate. Participants were maintained on a stable dose of methotrexate(10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and methotrexate (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a placebo administered monthly IV plus methotrexate. Participants were maintained on a stable dose of methotrexate (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and methotrexate(maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Overall Number of Participants Analyzed 115 105 119
Measure Type: Number
Unit of Measure: Participants
Day 15 30 9 24
Day 30 48 22 36
Day 60 65 35 41
Day 90 62 40 42
Day 120 71 47 45
Day 150 67 46 42
Day 180 70 44 42
Day 240 72 43 42
Day 300 73 41 41
Day 360 72 44 43
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DB Abatacept 10 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 15
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.283
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 5.9
Confidence Interval (2-Sided) 95%
-4.9 to 16.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DB Abatacept 2 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 15
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value -11.6
Confidence Interval (2-Sided) 95%
-20.9 to -2.3
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DB Abatacept 10 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 30
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.067
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 11.5
Confidence Interval (2-Sided) 95%
-0.8 to 23.8
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection DB Abatacept 2 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 30
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.113
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value -9.3
Confidence Interval (2-Sided) 95%
-20.8 to 2.2
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection DB Abatacept 10 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 60
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 22.1
Confidence Interval (2-Sided) 95%
9.3 to 34.8
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection DB Abatacept 2 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 60
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.86
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-13.5 to 11.3
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection DB Abatacept 10 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 90
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 18.6
Confidence Interval (2-Sided) 95%
5.9 to 31.4
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection DB Abatacept 2 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 90
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.664
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
-9.8 to 15.4
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection DB Abatacept 10 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 120
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 23.9
Confidence Interval (2-Sided) 95%
11.1 to 36.7
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection DB Abatacept 2 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 120
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.292
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 6.9
Confidence Interval (2-Sided) 95%
-6.0 to 19.9
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection DB Abatacept 10 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 150
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 23.0
Confidence Interval (2-Sided) 95%
10.2 to 35.8
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection DB Abatacept 2 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 150
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.193
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 8.5
Confidence Interval (2-Sided) 95%
-4.3 to 21.3
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection DB Abatacept 10 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 180
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 25.6
Confidence Interval (2-Sided) 95%
12.8 to 38.4
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection DB Abatacept 2 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 180
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.31
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 6.6
Confidence Interval 95%
-6.2 to 19.4
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection DB Abatacept 10 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 240
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 27.3
Confidence Interval (2-Sided) 95%
14.5 to 40.1
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection DB Abatacept 2 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 240
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.384
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 5.7
Confidence Interval (2-Sided) 95%
-7.1 to 18.4
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection DB Abatacept 10 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 300
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 29.0
Confidence Interval (2-Sided) 95%
16.2 to 41.8
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection DB Abatacept 2 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 300
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.476
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 4.6
Confidence Interval (2-Sided) 95%
-8.0 to 17.2
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection DB Abatacept 10 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 360
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 26.5
Confidence Interval (2-Sided) 95%
13.7 to 39.3
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection DB Abatacept 2 mg/kg + Methotrexate, DB Placebo + Methotrexate
Comments Response on Day 360
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.377
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 5.8
Confidence Interval (2-Sided) 95%
-7.0 to 18.6
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Number of ACR 50 Responders in DB Period
Hide Description ACR 50 response requires a participant 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, participant global assessment of disease, participant 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 30; Day 60; Day 90; Day 120; Day 150; Day 180; Day 240; Day 300; Day 360
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 infusion of study medication
Arm/Group Title Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX) Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate Double-Blind (DB) Placebo + Methotrexate
Hide Arm/Group Description:
Participants in the DB study received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a weight-tiered dose of 2 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a placebo that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Overall Number of Participants Analyzed 115 105 119
Measure Type: Number
Unit of Measure: Participants
Day 15 2 0 3
Day 30 16 4 7
Day 60 25 14 18
Day 90 28 18 15
Day 120 38 18 18
Day 150 42 18 19
Day 180 42 24 14
Day 240 41 22 24
Day 300 45 23 18
Day 360 48 24 24
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 15
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.679
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-4.5 to 2.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 15
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.101
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value -2.5
Confidence Interval (2-Sided) 95%
-5.5 to 0.5
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 30
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.039
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 8.0
Confidence Interval (2-Sided) 95%
0.4 to 15.7
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 30
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.474
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value -2.1
Confidence Interval (2-Sided) 95%
-7.7 to 3.6
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 60
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.192
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 6.6
Confidence Interval (2-Sided) 95%
-3.3 to 16.5
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 60
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.702
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-11.0 to 7.4
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 90
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 11.7
Confidence Interval (2-Sided) 95%
1.8 to 21.7
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 90
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.339
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 4.5
Confidence Interval (2-Sided) 95%
-4.8 to 13.8
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 120
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 17.9
Confidence Interval (2-Sided) 95%
7.0 to 28.9
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 120
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.682
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 2.0
Confidence Interval (2-Sided) 95%
-7.6 to 11.7
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 150
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 20.6
Confidence Interval (2-Sided) 95%
9.3 to 31.8
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 150
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.813
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-8.6 to 10.9
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 180
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 24.8
Confidence Interval (2-Sided) 95%
13.8 to 35.7
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 180
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.027
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 11.1
Confidence Interval (2-Sided) 95%
1.2 to 20.9
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 240
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 15.5
Confidence Interval (2-Sided) 95%
4.0 to 27.0
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 240
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.885
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-9.8 to 11.4
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 300
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 24.0
Confidence Interval (2-Sided) 95%
12.6 to 35.4
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 300
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.19
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 6.8
Confidence Interval (2-Sided) 95%
-3.4 to 16.9
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 360
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 21.6
Confidence Interval (2-Sided) 95%
9.7 to 33.4
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 360
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.625
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 2.7
Confidence Interval (2-Sided) 95%
-8.1 to 13.5
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Number of ACR 70 Responders in DB Period
Hide Description ACR 70 response requires a participant 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, participant global assessment of disease, participant assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in HAQ score. A participant achieved a sustained ACR 70 response if the participant had ACR 70 observed for at least 2 consecutive study visits.
Time Frame Day 15; Day 30; Day 60; Day 90; Day 120; Day 150; Day 180; Day 240; Day 300; Day 360
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 infusion of study medication
Arm/Group Title Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX) Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate Double-Blind (DB) Placebo + Methotrexate
Hide Arm/Group Description:
Participants in the DB study received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a weight-tiered dose of 2 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a placebo that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Overall Number of Participants Analyzed 115 105 119
Measure Type: Number
Unit of Measure: Participants
Day 15 0 0 0
Day 30 4 3 0
Day 60 10 4 0
Day 90 10 5 1
Day 120 15 6 4
Day 150 16 6 4
Day 180 19 11 2
Day 240 21 9 6
Day 300 27 11 3
Day 360 24 13 9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 30
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 3.5
Confidence Interval 95%
0.2 to 6.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 30
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.063
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 2.9
Confidence Interval (2-Sided) 95%
-0.2 to 5.9
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 60
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 8.7
Confidence Interval (2-Sided) 95%
3.5 to 13.9
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 60
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.032
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 3.8
Confidence Interval (2-Sided) 95%
0.3 to 7.3
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 90
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 7.9
Confidence Interval (2-Sided) 95%
2.4 to 13.3
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 90
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 3.9
Confidence Interval (2-Sided) 95%
-0.3 to 8.2
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 120
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 9.7
Confidence Interval (2-Sided) 95%
2.7 to 16.7
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.395
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 2.4
Confidence Interval 95%
-3.1 to 7.8
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 150
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 10.6
Confidence Interval (2-Sided) 95%
3.4 to 17.7
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 150
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.395
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 2.4
Confidence Interval (2-Sided) 95%
-3.1 to 7.8
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 180
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 14.8
Confidence Interval (2-Sided) 95%
7.5 to 22.2
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 180
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 8.8
Confidence Interval (2-Sided) 95%
2.7 to 14.9
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 240
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 13.2
Confidence Interval (2-Sided) 95%
5.0 to 21.4
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 240
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.292
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 3.5
Confidence Interval (2-Sided) 95%
-3.0 to 10.1
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 300
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 21.0
Confidence Interval (2-Sided) 95%
12.4 to 29.5
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 300
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 8.0
Confidence Interval (2-Sided) 95%
1.6 to 14.3
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 360
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 13.3
Confidence Interval (2-Sided) 95%
4.4 to 22.2
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Response on Day 360
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.227
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate of Difference
Estimated Value 4.8
Confidence Interval (2-Sided) 95%
-3.0 to 12.6
Estimation Comments [Not Specified]
18.Secondary Outcome
Title ACR Numeric Values (ACR-N)
Hide Description The ACR-N is calculated for each participant by taking the lowest percentage improvement in (1) swollen joint count or (2) tender joint count or (3) the median of the remaining 5 components of the ACR response (participant’s assessment of disease activity; participant’s global assessment of pain; physician’s assessment of disease activity; participant’s assessment of physical function; an acute phase reactant value - CRP). Negative numbers indicate worsening.
Time Frame Day 15; Day 30; Day 60; Day 90; Day 120; Day 150; Day 180; Day 240; Day 300; Day 360
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 infusion of study medication
Arm/Group Title Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX) Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate Double-Blind (DB) Placebo + Methotrexate
Hide Arm/Group Description:
Participants in the DB study received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a weight-tiered dose of 2 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a placebo that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Overall Number of Participants Analyzed 115 105 119
Mean (Standard Deviation)
Unit of Measure: units on a scale
Day 15 (n=113, 104, 118) 11.09  (15.53) 5.26  (10.37) 9.07  (14.76)
Day 30 (n=115, 104, 117) 20.45  (23.41) 12.06  (18.11) 13.20  (17.85)
Day 60 (n=114, 105, 119) 28.85  (26.78) 17.69  (22.83) 17.09  (20.90)
Day 90 (n=115, 105, 118) 29.03  (27.38) 21.12  (26.10) 16.93  (21.61)
Day 120 (n=114, 105, 115) 33.80  (29.35) 22.87  (26.10) 19.26  (23.70)
Day 150 (n=114, 103, 118) 36.34  (30.29) 22.69  (24.15) 19.37  (24.74)
Day 180 (n=114, 104, 118) 37.65  (30.39) 24.67  (29.03) 17.29  (22.02)
Day 240 (n=115, 104, 119) 38.34  (31.49) 23.49  (27.51) 20.71  (25.97)
Day 300 (n=114, 105, 119) 39.69  (31.08) 21.82  (27.99) 18.69  (23.53)
Day 360 (n=115, 105, 119) 40.87  (31.69) 24.55  (29.37) 20.49  (26.14)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Day 15 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2676
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.02
Confidence Interval (2-Sided) 95%
-1.56 to 5.61
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Day 15 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0418
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.80
Confidence Interval (2-Sided) 95%
-7.46 to -0.14
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Day 30 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0061
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.25
Confidence Interval (2-Sided) 95%
2.08 to 12.41
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Day 30 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6713
Comments ANOVA model: AUC = treatment
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.14
Confidence Interval (2-Sided) 95%
-6.45 to 4.16
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Day 60 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 11.75
Confidence Interval (2-Sided) 95%
5.67 to 17.84
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Day 60 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8495
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
-5.62 to 6.82
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Day 90 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 12.10
Confidence Interval (2-Sided) 95%
5.63 to 18.56
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Day 90 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.19
Confidence Interval (2-Sided) 95%
-2.44 to 10.81
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Day 120 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 14.54
Confidence Interval (2-Sided) 95%
7.28 to 21.81
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Day 120 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3141
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.60
Confidence Interval (2-Sided) 95%
-3.43 to 10.64
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Day 150 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 16.96
Confidence Interval (2-Sided) 95%
8.49 to 25.43
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Day 150 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3552
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.32
Confidence Interval (2-Sided) 95%
-3.73 to 10.37
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Day 180 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 20.36
Confidence Interval (2-Sided) 95%
10.19 to 30.54
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Day 180 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0451
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.38
Confidence Interval (2-Sided) 95%
0.16 to 14.60
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Day 240 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 17.63
Confidence Interval (2-Sided) 95%
8.83 to 26.44
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Day 240 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4669
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.78
Confidence Interval (2-Sided) 95%
-4.73 to 10.28
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Day 300 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 21.00
Confidence Interval (2-Sided) 95%
10.51 to 31.48
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Day 300 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 3.13
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.13
Confidence Interval (2-Sided) 95%
-4.15 to 10.41
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Day 360 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 20.38
Confidence Interval (2-Sided) 95%
10.20 to 30.56
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Day 360 Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2989
Comments [Not Specified]
Method ANOVA
Comments ANOVA model: AUC = treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.06
Confidence Interval (2-Sided) 95%
-3.61 to 11.72
Estimation Comments Estimate= Model AUC for abatacept+methotrexate - Model AUC for placebo+methotrexate
19.Secondary Outcome
Title ACR-N Area Under The Curve (AUC) on Day 180 and Day 360
Hide Description The AUC for ACR-N is the measure of the area under the curve of the mean change from baseline in ACR-N. The trapezoidal rule was used to compute the AUC. The ACR-N AUC was compared between the two abatacept treatment groups and the placebo group using an analysis of variance (ANOVA) for 6- and 12-month data (Day 180 and Day 360). This allowed for the assessment of subject response throughout the study. See Measure Description in Outcome Measure 18 for a definition of ACR-N.
Time Frame Baseline and Day 180; Baseline and Day 360
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX) Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate Double-Blind (DB) Placebo + Methotrexate
Hide Arm/Group Description:
Participants in the DB study received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a weight-tiered dose of 2 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a placebo that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Overall Number of Participants Analyzed 115 105 119
Mean (Standard Error)
Unit of Measure: percentage*days
Day 180 5021.70  (317.9) 3242.54  (332.7) 2889.07  (312.5)
Day 360 12035.1  (711.7) 7447.87  (744.8) 6393.49  (699.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Comparison at Day 180
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments ANOVA model: AUC = treatment
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2132.63
Confidence Interval (2-Sided) 95%
1067.32 to 3197.94
Estimation Comments Estimate = Model AUC for Aripiprazole+MTX - Model AUC for PLACEBO+MTX
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Comparison at Day 180
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4393
Comments ANOVA model: AUC = treatment
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 353.47
Confidence Interval (2-Sided) 95%
-544.46 to 1251.41
Estimation Comments Estimate = Model AUC for Aripiprazole+MTX - Model AUC for PLACEBO+MTX
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Comparison at Day 360
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments ANOVA model: AUC = treatment
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5641.60
Confidence Interval (2-Sided) 95%
2823.46 to 8459.74
Estimation Comments Estimate = Model AUC for Aripiprazole+MTX - Model AUC for PLACEBO+MTX
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Comparison at Day 360
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3029
Comments ANOVA model: AUC = treatment
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1054.38
Confidence Interval (2-Sided) 95%
-955.59 to 3064.35
Estimation Comments Estimate = Model AUC for Aripiprazole+MTX - Model AUC for PLACEBO+MTX
20.Secondary Outcome
Title Individual Components of ACR Criteria--Mean Percentage Change From Baseline at Day 180
Hide Description Percentage change = 100*(Baseline value – value at specific visit) / Baseline value. The American College of Rheumatology (ACR) response criteria, based on a core set of variables which includes a tender joint count, a swollen joint count, patient-reported pain scale (Subject Assessment of Physical Function [SAPF]), patient and physician global assessments of disease activity (Subject Global Assessment [SGA] and Physician Global Assessment [PGA]), patient assessment of functional ability, and an acute phase reactant (C-Reactive Protein [CRP])
Time Frame Baseline, Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed = Participants who received at least 1 infusion of study medication; n = subset of participants who had given measurement at both time points.
Arm/Group Title Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX) Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate Double-Blind (DB) Placebo + Methotrexate
Hide Arm/Group Description:
Participants in the DB study received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a weight-tiered dose of 2 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a placebo that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Overall Number of Participants Analyzed 115 105 119
Mean (Standard Error)
Unit of Measure: percentage change
Tender Joints (n=114, 104, 118) 59.8  (3.6) 43.2  (4.1) 31.9  (5.0)
Swollen Joints (n=114, 104, 118) 55.3  (3.5) 45.3  (4.1) 33.5  (4.3)
Pain (n=109, 102, 118) 46.2  (4.1) 22.1  (5.8) 8.2  (7.0)
SAPF (n=107, 98, 110) 41.2  (4.6) 21.6  (6.5) 13.7  (5.5)
Subject Global Assessment (n=111, 103, 118) 40.8  (4.7) 9.1  (10.4) 17.5  (4.1)
Physician Global Assessment (n=111, 103, 116) 51.9  (3.4) 38.7  (4.4) 25.1  (3.5)
C-Reactive Protein (n=108, 98, 114) 31.8  (6.3) 16.4  (7.0) -23.4  (11.0)
21.Secondary Outcome
Title Individual Components of ACR Criteria--Mean Percentage Change From Baseline at Day 360
Hide Description Percentage change = 100*(Baseline value – value at specific visit) / Baseline value. The American College of Rheumatology (ACR) response criteria, based on a core set of variables which includes a tender joint count, a swollen joint count, patient-reported pain scale (Subject Assessment of Physical Function [SAPF]), patient and physician global assessments of disease activity (Subject Global Assessment [SGA] and Physician Global Assessment [PGA]), patient assessment of functional ability, and an acute phase reactant (C-Reactive Protein [CRP])
Time Frame Baseline, Day 360
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed = Participants who received at least 1 infusion of study medication; n = subset of participants who had given measurement at both time points.
Arm/Group Title Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX) Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate Double-Blind (DB) Placebo + Methotrexate
Hide Arm/Group Description:
Participants in the DB study received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a weight-tiered dose of 2 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a placebo that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Overall Number of Participants Analyzed 115 105 119
Mean (Standard Error)
Unit of Measure: percentage change
Tender Joints (n=114, 104, 118) 66.4  (3.8) 43.6  (4.3) 30.0  (5.3)
Swollen Joints (n=114, 104, 118) 59.7  (3.7) 46.4  (4.5) 36.2  (4.4)
Pain (n=109, 102, 118) 44.9  (4.7) 26.2  (5.9) 65.2  (12.6)
SAPF (n=107, 98, 110) 42.3  (4.3) 22.9  (5.0) 10.3  (5.9)
Subject Global Assessment (n=111, 103, 118) 41.0  (5.1) 16.0  (8.9) 2.0  (19.1)
Physician Global Assessment (n=111, 103, 116) 53.5  (3.4) 37.9  (4.2) 24.1  (3.8)
C-Reactive Protein (n=108, 98, 114) 27.6  (9.9) 11.0  (9.5) -31.3  (12.6)
22.Secondary Outcome
Title Mean Changes From Baseline in the Short Form 36 (SF-36) Physical and Mental Health Component Summary Scores (PCS and MCS) at Day 180 and Day 360
Hide Description SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0=worst score (or quality of life) and 100=best score.
Time Frame Baseline, Day 180, Day 360
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=total number of participants in each treatment group. n=number of treated Participants with measurement at baseline and given timepoint.
Arm/Group Title Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX) Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate Double-Blind (DB) Placebo + Methotrexate
Hide Arm/Group Description:
Participants in the DB study received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a weight-tiered dose of 2 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a placebo that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Overall Number of Participants Analyzed 115 105 119
Mean (Standard Error)
Unit of Measure: units on a scale
PCS, Mean Change at Day 180 (n=115, 104, 119) 8.3  (0.9) 4.6  (0.7) 3.0  (0.6)
MCS, Mean Change at Day 180 (n=115, 104, 119) 5.0  (1.0) 2.7  (1.2) 3.2  (1.0)
PCS, Mean Change at Day 360 (n=115, 104, 119) 8.1  (0.9) 5.3  (0.8) 2.8  (0.7)
PCS, Mean Change at Day 360 (n=115, 104, 119) 5.7  (1.0) 3.5  (1.1) 3.0  (0.9)
23.Secondary Outcome
Title Adjusted Mean Percent Changes From Baseline in the Modified Health Assessment Questionnaire (mHAQ) at Day 180 and Day 360
Hide Description A shortened version of the Health Assessment Questionnaire (HAQ), which uses only 8 instead of the 20 original items and is used to assess motor performance in everyday activities, such as dressing, turning a faucet on/off, and getting in and out of a car. Percent change from baseline = (baseline - post baseline value) / baseline value x 100.
Time Frame Baseline, Day 180, Day 360
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=total number of participants in each treatment group. n=number of treated Participants with measurement at baseline and given timepoint.
Arm/Group Title Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX) Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate Double-Blind (DB) Placebo + Methotrexate
Hide Arm/Group Description:
Participants in the DB study received a weight-tiered dose of 10 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a weight-tiered dose of 2 mg/kg of abatacept that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Participants in the DB study received a placebo that was administered monthly by an intravenous (IV) plus methotrexate (MTX).Participants were maintained on a stable dose of MTX (10-30 mg/wk) during Days 1 to 180 of the DB period; adjustments in corticosteroids (maximum 10 mg/day) and MTX (maximum 30 mg/wk) were permitted (as well as addition of either hydroxychloroquine, sulfasalazine, gold or azathioprine) during Days 181 to 360 of the DB period.
Overall Number of Participants Analyzed 115 105 119
Mean (Standard Error)
Unit of Measure: Percentage of Change on mHAQ scale
Mean Percentage Change at Day 180 (n=107, 98, 110) 41.39  (5.43) 21.41  (5.67) 13.73  (5.35)
Mean PercentageChange at Day 360 (n=109, 100, 111) 42.49  (5.05) 22.74  (5.27) 10.26  (5.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Day 180
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA: % change = pretreatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 27.66
Confidence Interval (2-Sided) 95%
12.67 to 42.66
Estimation Comments Estimate = adjusted % change (BMS10mg/kg+MTX or BMS 2mg/kg+MTX) - adjusted change for placebo+MTX
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Day 180
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3253
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: % change = pretreatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.68
Estimation Comments Estimate = adjusted % change (BMS10mg/kg+MTX or BMS 2mg/kg+MTX) - adjusted change for placebo+MTX
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Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 10 mg/kg + Methotrexate (MTX), Double-Blind (DB) Placebo + Methotrexate
Comments Day 360
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: % change = pretreatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 32.24
Confidence Interval (2-Sided) 95%
16.14 to 48.33
Estimation Comments Estimate = adjusted % change (BMS10mg/kg+MTX or BMS 2mg/kg+MTX) - adjusted change for placebo+MTX
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Statistical Analysis Overview Comparison Group Selection Double-Blind (DB) Abatacept 2 mg/kg + Methotrexate, Double-Blind (DB) Placebo + Methotrexate
Comments Day 360
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0869
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: % change = pretreatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 12.48
Confidence Interval (2-Sided) 95%
-1.82 to 26.78
Estimation Comments Estimate = adjusted % change (BMS10mg/kg+MTX or BMS 2mg/kg+MTX) - adjusted change for placebo+MTX
24.Secondary Outcome
Title Number of Participants With At Least One New Active Joint (Tender Joints and Swollen Joints) at Day 180 and Day 360
Hide Description [Not Specified]
Time Frame Day 180, Day 360
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Double