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Trial record 43 of 137 for:    "Connective Tissue Disease" | "Abatacept"

Efficacy and Safety Study of Abatacept Subcutaneous Plus Methotrexate in Inducing Remission in Adults With Very Early Rheumatoid Arthritis

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ClinicalTrials.gov Identifier: NCT01142726
Recruitment Status : Completed
First Posted : June 11, 2010
Results First Posted : October 17, 2014
Last Update Posted : January 14, 2016
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: Abatacept
Drug: Methotrexate
Drug: Abatacept placebo
Drug: Methotrexate placebo
Enrollment 511
Recruitment Details  
Pre-assignment Details A total of 511 patients were enrolled in the study, and 351 were randomized. The primary reasons that 160 enrolled patients were not randomized were failure to meet study criteria (130/160) and withdrawal of consent (20/160).
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description Participants received abatacept, 125 mg subcutaneously, plus methotrexate (MTX), 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept subcutaneous (SC) 125 mg/week and MTX. Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Period Title: Treatment Phase: Day 1 Through Month 12
Started 119 116 116
Completed 103 91 96
Not Completed 16 25 20
Reason Not Completed
Adverse Event             5             8             5
Withdrawal by Subject             4             9             3
Lost to Follow-up             1             2             1
Poor compliance/noncompliance             1             0             0
Lack of Efficacy             5             6             11
Period Title: Withdrawal Phase: Months 12 up to 24
Started 84 66 75
Completed 14 10 17
Not Completed 70 56 58
Reason Not Completed
Adverse Event             0             0             1
Withdrawal by Subject             1             1             2
Pregnancy             1             0             1
Lost to Follow-up             2             0             0
No longer met study criteria             1             0             0
Lack of Efficacy             65             54             53
non-specified             0             1             1
Period Title: Re-Exposure Phase: Months 24 up to 30
Started 55 48 43
Completed 54 46 40
Not Completed 1 2 3
Reason Not Completed
Adverse Event             0             0             1
Withdrawal by Subject             1             1             1
Pregnancy             0             0             1
Lack of Efficacy             0             1             0
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo Total
Hide Arm/Group Description Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period Total of all reporting groups
Overall Number of Baseline Participants 119 116 116 351
Hide Baseline Analysis Population Description
All randomized patients who received at least 1 dose of double-blind study medication in the Treatment Period
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 119 participants 116 participants 116 participants 351 participants
46.4  (13.20) 45.4  (11.92) 49.1  (12.36) 47.0  (12.57)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 119 participants 116 participants 116 participants 351 participants
Female
95
  79.8%
89
  76.7%
89
  76.7%
273
  77.8%
Male
24
  20.2%
27
  23.3%
27
  23.3%
78
  22.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 119 participants 116 participants 116 participants 351 participants
White 100 95 102 297
Asian 14 13 9 36
Black/African American 2 4 2 8
American Indian/Alaska native 1 1 1 3
Other 2 3 2 7
Duration of rheumatoid arthritis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 119 participants 116 participants 116 participants 351 participants
0.58  (0.500) 0.59  (0.522) 0.50  (0.488) 0.56  (0.504)
Disease Activity Score 28 based on C-reactive protein (DAS28-CRP)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 119 participants 116 participants 116 participants 351 participants
5.528  (1.2501) 5.463  (1.1493) 5.315  (1.3330) 5.435  (1.2465)
[1]
Measure Description: The DAS28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient’s global assessment of health (ranging from very good to very bad). These measures are then fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
Health Assessment Questionnaire Disability Index (HAQ-DI) score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 119 participants 116 participants 116 participants 351 participants
1.452  (0.6778) 1.419  (0.6587) 1.383  (0.6493) 1.419  (0.6609)
[1]
Measure Description: The HAQ-DI assesses patients' functional ability by rating their abilities over the previous week. It includes at least 2 questions from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities. Patients rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The sum of the categories score (the highest scored item in the category) is divided by the number of categories answered, yielding a score from 0-3.
Rheumatoid factor status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 119 participants 116 participants 116 participants 351 participants
Positive 113 111 110 334
Negative 6 5 6 17
Tender joint count  
Mean (Standard Deviation)
Unit of measure:  Joints
Number Analyzed 119 participants 116 participants 116 participants 351 participants
24.3  (15.74) 23.9  (14.47) 21.7  (14.00) 23.3  (14.77)
Swollen joint count  
Mean (Standard Deviation)
Unit of measure:  Joints
Number Analyzed 119 participants 116 participants 116 participants 351 participants
16.5  (12.43) 17.2  (12.88) 15.7  (11.78) 16.5  (12.35)
1.Primary Outcome
Title Percentage of Participants Who Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18
Hide Description DAS28-CRP remission defined as <2.6; TP=treatment phase; WP=withdrawal phase. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient’s global assessment of health (ranging from very good to very bad). These measures are then fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
Time Frame Randomization to Months 12 and 18
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. Percentage calculated as a/b, where a=number of patients who achieved remission at Month 12 and at both Months 12 and 18, and b=number of patients in the analysis. n=number evaluable
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:
Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Overall Number of Participants Analyzed 119 116
Measure Type: Number
Unit of Measure: Percentage of participants
Month 12 (TP Day 365) (n=115, 115) 60.9 45.2
Both Months 12 & 18 (WP Day 169) (n=115, 115) 14.8 7.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept, 125 mg, Plus Methotrexate, 2.5 mg, Methotrexate, 2.5 mg, Plus Abatacept Placebo
Comments Power estimate assumed 2-sided alpha level of 5% and that 60% of abatacept (ABA)+methotrexate (MX) patients (pts) would be in DAS28-CRP remission at Month 12 compared with 38% of MX monotherapy pts. Also assumed that 48% of ABA monotherapy pts would be in DAS28-CRP remission at Month 12, yielding an expected treatment difference from MX of 10% in favor of ABA monotherapy; 116 pts randomized to ABA monotherapy would yield a half-length of the 95% CI around that 10% treatment difference of 13.5%.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments [Not Specified]
Method Regression, Logistic
Comments Statistical testing of the 2 coprimary efficacy endpoints was conducted in a hierarchical fashion to maintain the overall Type I error rate at 5%.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.01
Confidence Interval (2-Sided) 95%
1.18 to 3.43
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.55
Estimation Comments At Month 12
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Abatacept, 125 mg, Plus Methotrexate, 2.5 mg, Methotrexate, 2.5 mg, Plus Abatacept Placebo
Comments Conditional on statistical significance of the 1st coprimary efficacy analysis (CEA), a sample of 116 patients per arm would provide 98% power for the 2nd CEA comparison of the percentage of patients in DAS28-CRP remission at Months 12 and 18 between the abatacept (ABA)+methotrexate (MTX) arm and the MTX monotherapy arm for intent-to treat population. This sample size calculation assumed 30% remission in the ABA+MTX arm and 8% in the monotherapy arm at Month 18 and a 2-sided alpha level of 5%.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.045
Comments [Not Specified]
Method Regression, Logistic
Comments Statistical testing of the 2 coprimary efficacy endpoints was conducted in a hierarchical fashion to maintain the overall Type I error rate at 5%.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.51
Confidence Interval (2-Sided) 95%
1.02 to 6.18
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.15
Estimation Comments At Months 12 and 18
2.Secondary Outcome
Title Percentage of Participants Who Received Monotherapy and Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18
Hide Description TP=treatment period; WP=withdrawal period. Remission defined as DAS28-CRP<2.6. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient’s global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
Time Frame Randomization to Months 12 and 18
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of double-blind monotherapy in the Treatment Period. Percentage calculated as a/b, where a=number of patients who achieved remission at Month 12 and at both Months 12 and 18, and b=number of patients in the analysis. n=number evaluable
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Overall Number of Participants Analyzed 116 116
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
At Month 12 (TP Day 365) (n=113, 115)
42.5
(33.36 to 51.59)
45.2
(36.12 to 54.31)
At both Months 12 &18 (WP Day 169) (n=113, 115)
12.4
(6.31 to 18.46)
7.8
(2.92 to 12.73)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept, 125 mg, Plus Methotrexate Placebo, Methotrexate, 2.5 mg, Plus Abatacept Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.55 to 1.57
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.25
Estimation Comments At Month 12
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Abatacept, 125 mg, Plus Methotrexate Placebo, Methotrexate, 2.5 mg, Plus Abatacept Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.04
Confidence Interval (2-Sided) 95%
0.81 to 5.14
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.96
Estimation Comments At Months 12 and 18
3.Secondary Outcome
Title Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population
Hide Description TP=treatment period; WP=withdrawal period. Remission defined as DAS28-CRP<2.6. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient’s global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
Time Frame Randomization to Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. Percentage calculated as a/b, where a=number of patients who achieved remission at Day x, and b=number of patients in the analysis (intent to treat).
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:
Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Overall Number of Participants Analyzed 119 116 116
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
TP Day 29
13.4
(7.32 to 19.57)
8.6
(3.51 to 13.73)
6.0
(1.70 to 10.37)
TP Day 57
24.4
(16.66 to 32.08)
11.2
(5.47 to 16.95)
9.5
(4.15 to 14.81)
TP Day 85
36.1
(27.50 to 44.77)
21.6
(14.07 to 29.03)
17.2
(10.37 to 24.12)
TP Day 113
37.8
(29.10 to 46.53)
29.3
(21.03 to 37.59)
19.0
(11.83 to 26.10)
TP Day 141
45.4
(36.43 to 54.32)
29.3
(21.03 to 37.59)
25.0
(17.12 to 32.88)
TP Day 169
45.4
(36.43 to 54.32)
32.8
(24.22 to 41.30)
26.7
(18.67 to 34.78)
TP Day 197
52.1
(43.13 to 61.08)
36.2
(27.46 to 44.95)
25.9
(17.89 to 33.83)
TP Day 225
57.1
(48.25 to 66.03)
40.5
(31.58 to 49.45)
30.2
(21.82 to 38.53)
TP Day 253
62.2
(53.47 to 70.90)
37.9
(29.10 to 46.76)
30.2
(21.82 to 38.53)
TP 281
51.3
(42.28 to 60.24)
42.2
(33.25 to 51.23)
32.8
(24.22 to 41.30)
TP 309
56.3
(47.39 to 65.21)
37.9
(29.10 to 46.76)
36.2
(27.46 to 44.95)
TP Day 337
63.0
(54.35 to 71.70)
43.1
(34.09 to 52.12)
33.6
(25.02 to 42.22)
TP 365
61.3
(52.60 to 70.09)
43.1
(34.09 to 52.12)
45.7
(36.62 to 54.75)
WP Day 29
51.3
(42.28 to 60.24)
36.2
(27.46 to 44.95)
27.6
(19.45 to 35.72)
WP Day 57
40.3
(31.52 to 49.15)
25.0
(17.12 to 32.88)
18.1
(11.10 to 25.11)
WP Day 85
31.1
(22.78 to 39.41)
18.1
(11.10 to 25.11)
18.1
(11.10 to 25.11)
WP Day 169
19.3
(12.23 to 26.42)
12.9
(6.82 to 19.04)
9.5
(4.15 to 14.81)
WP Day 253
17.6
(10.80 to 24.50)
9.5
(4.15 to 14.81)
13.8
(7.52 to 20.07)
WP Day 365
9.2
(4.04 to 14.45)
6.0
(1.70 to 10.37)
6.0
(1.70 to 10.37)
4.Secondary Outcome
Title Adjusted Mean Change From Baseline in Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) at Months 6, 12, and 18
Hide Description TP=treatment period; WP=withdrawal period. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient’s global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
Time Frame Baseline to Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. n=number evaluable
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:
Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Overall Number of Participants Analyzed 119 116 116
Mean (Standard Error)
Unit of Measure: Units on a scale
Month 6 (TP Day 169) (n=102, 96, 101) -2.72  (0.12) -2.33  (0.12) -1.93  (0.12)
Month 12 (TP Day 365) (n=95, 84, 91) -3.09  (0.13) -2.75  (0.13) -2.58  (0.13)
Month 18 (WP Day 169) (n=41, 31, 32) -1.54  (0.26) -1.51  (0.29) -1.06  (0.29)
5.Secondary Outcome
Title Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) at Months 12 and 18
Hide Description TP=treatment period; WP=withdrawal period. SDAI-defined remission= ≤3.3. The SDAI is the simple linear sum of 5 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) (based on a 28-joint assessment); patient's and physician's global assessments of disease activity (assessed on 0-10 cm visual analog scale, on which higher scores=greater affection due to disease activity); and C-reactive protein level (mg/dL). SDAI total score=0-86. SDAI <=3.3 indicates disease remission, >3.4 to 11=low disease activity, >11 to 26=moderate disease activity, and >26=high disease activity. TJC is assessed and recorded at each visit, with no swelling=0, swelling=1. SJC is assessed through identification of joints that are painful under pressure or to passive motion. TJC is recorded on the joint assessment form at each visit, with no tenderness =0, tenderness = 1. Higher score indicates greater affection due to disease activity.
Time Frame Randomization to Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. Percentage calculated as a/b, where a=number of patients who achieved remission at Months 12 and 18, and b=number of patients in the analysis.
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:
Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Overall Number of Participants Analyzed 119 116 116
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Month 12 (TP Day 365)
42.0
(33.15 to 50.89)
29.3
(21.03 to 37.59)
25.0
(17.12 to 32.88)
Month 18 (WP Day 169)
10.9
(5.32 to 16.53)
8.6
(3.51 to 13.73)
6.9
(2.29 to 11.51)
6.Secondary Outcome
Title Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time
Hide Description TP=treatment period; WP=withdrawal period. The SDAI is the simple linear sum of 5 outcome parameters: swollen joint count (SJC) and tender joint count (TJC) (based on a 28-joint assessment); patient's and physician's global assessments of disease activity (assessed on 0-10 cm visual analog scale, on which higher scores=greater affection due to disease activity); and C-reactive protein level (mg/dL). SDAI total score=0-86. SJC is assessed and recorded at each visit, with no swelling=0, swelling=1 (higher score indicates greater swelling). TJC is assessed at each visit through identification of joints that are painful under pressure or to passive motion, with no tenderness=0, tenderness=1 (higher score indicates greater affection due to disease activity)..
Time Frame Randomization to Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population. n= number of participants with both post baseline and baseline measurements.
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:
Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Overall Number of Participants Analyzed 119 116 116
Mean (Standard Error)
Unit of Measure: Units on a scale
TP Day 29 (n=109, 101, 107) -13.11  (1.33) -12.14  (1.37) -10.12  (1.33)
TP Day 57 (n=108, 101, 103) -18.90  (1.25) -15.83  (1.28) -15.99  (1.26)
TP Day 85 (n=108, 99, 103) -24.13  (1.16) -20.51  (1.20) -19.55  (1.17)
TP Day 113 (n=103, 98, 101) -25.47  (1.12) -23.56  (1.15) -21.02  (1.13)
TP Day 141 (n=104, 96, 104) -27.15  (1.10) -25.99  (1.13) -22.14  (1.10)
TP Day 169 (n=102, 96, 100) -28.42  (1.08) -26.20  (1.11) -22.80  (1.09)
TP Day 197 (n=103, 97, 96) -29.66  (1.01) -27.57  (1.03) -24.37  (1.02)
TP Day 225 (n=99, 94, 92) -30.13  (1.04) -28.39  (1.06) -24.73  (1.06)
TP Day 253 (n=98, 94, 91) -31.14  (1.04) -28.10  (1.06) -25.80  (1.05)
TP 281 (n=96, 93, 89) -30.98  (1.10) -28.16  (1.12) -26.23  (1.12)
TP 309 (n=91, 87, 92) -30.82  (1.16) -27.79  (1.18) -26.36  (1.17)
TP Day 337 (n=93, 84, 87) -31.11  (1.15) -29.34  (1.19) -27.26  (1.17)
TP 365 (n=95, 84, 91) -31.24  (1.17) -28.88  (1.21) -28.34  (1.19)
WP Day 29 (n=73, 59, 64) -30.42  (1.32) -28.05  (1.39) -23.52  (1.36)
WP Day 57 (n=69, 54, 59) -27.68  (1.59) -24.17  (1.74) -17.94  (1.68)
WP Day 85 (n=67, 47, 52) -22.00  (2.18) -21.55  (2.57) -17.54  (2.44)
WP Day 169 (n=41, 31, 32) -17.43  (2.82) -19.13  (3.25) -13.64  (3.19)
7.Secondary Outcome
Title Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time
Hide Description HAQ response defined as a reduction of at least 0.3 units from baseline in score on the Health Assessment Questionnaire Disability Index (HAQ-DI), which assesses patients' functional ability by rating their abilities over the previous week. The HAQ-DI includes at least 2 questions from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities. Patients rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The sum of the categories score (the highest scored item in the category) is divided by the number of categories answered, yielding a score from 0-3. When aids, devices, or help is indicated by the patient, the score for the category item is raised from a 0 or a 1 to a 2, but if the patient's highest score for a subcategory is a 3, it stays a 3.
Time Frame Randomization to Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. Percentage calculated as a/b, where a=number of patients who achieved remission at Day x, and b=number of patients in the analysis.
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:
Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Overall Number of Participants Analyzed 119 116 116
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
TP Day 29
42.0
(33.15 to 50.89)
31.0
(22.62 to 39.45)
21.6
(14.07 to 29.03)
TP Day 57
55.5
(46.53 to 64.39)
44.0
(34.93 to 53.00)
37.9
(29.10 to 46.76)
TP Day 85
63.0
(54.35 to 71.70)
45.7
(36.62 to 54.75)
41.4
(32.42 to 50.34)
TP Day 113
63.0
(54.35 to 71.70)
49.1
(40.04 to 58.24)
45.7
(36.62 to 54.75)
TP Day 141
62.2
(53.47 to 70.90)
51.7
(42.63 to 60.82)
44.0
(34.93 to 53.00)
TP Day 169
63.9
(55.23 to 72.50)
56.0
(47.00 to 65.07)
41.4
(32.42 to 50.34)
TP Day 197
66.4
(57.90 to 74.87)
59.5
(50.55 to 68.42)
41.4
(32.42 to 50.34)
TP Day 225
66.4
(57.90 to 74.87)
57.8
(48.77 to 66.75)
38.8
(29.93 to 47.66)
TP Day 253
68.9
(60.59 to 77.22)
55.2
(46.12 to 64.22)
45.7
(36.62 to 54.75)
TP Day 281
64.7
(56.12 to 73.29)
56.9
(47.88 to 65.91)
46.6
(37.47 to 55.63)
TP Day 309
65.5
(57.01 to 74.08)
56.9
(47.88 to 65.91)
46.6
(37.47 to 55.63)
TP Day 337
64.7
(56.12 to 73.29)
55.2
(46.12 to 64.22)
46.6
(37.47 to 55.63)
TP Day 365
67.2
(58.79 to 75.66)
52.6
(43.50 to 61.67)
44.0
(34.93 to 53.00)
WP Day 29
52.1
(43.13 to 61.08)
39.7
(30.75 to 48.56)
37.1
(28.28 to 45.86)
WP Day 57
43.7
(34.79 to 52.61)
34.5
(25.83 to 43.13)
26.7
(18.67 to 34.78)
WP Day 85
39.5
(30.71 to 48.28)
28.4
(20.24 to 36.66)
23.3
(15.59 to 30.97)
WP Day 169
22.7
(15.16 to 30.21)
16.4
(9.64 to 23.11)
10.3
(4.80 to 15.89)
WP Day 253
15.1
(8.69 to 21.56)
9.5
(4.15 to 14.81)
6.9
(2.29 to 11.51)
WP Day 365
10.1
(4.67 to 15.49)
6.9
(2.29 to 11.51)
5.2
(1.14 to 9.20)
8.Secondary Outcome
Title Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time
Hide Description The Health Assessment Questionnaire Disability Index (HAQ-DI) assesses patients' functional ability by rating their abilities over the previous week. The HAQ-DI includes at least 2 questions from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities. Patients rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The sum of the categories score (the highest scored item in the category) is divided by the number of categories answered, yielding a score from 0-3. When aids, devices, or help is indicated by the patient, the score for the category item is raised from a 0 or a 1 to a 2, but if the patient's highest score for a subcategory is a 3, it stays a 3.
Time Frame Randomization to Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. n=number evaluable
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:
Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Overall Number of Participants Analyzed 119 116 116
Mean (Standard Error)
Unit of Measure: Units on a scale
TP Day 29 (n=104, 103, 91) -0.33  (0.05) -0.21  (0.05) -0.09  (0.05)
TP Day 57 (n=102, 100, 93) -0.48  (0.05) -0.38  (0.05) -0.32  (0.05)
TP Day 85 (n=105, 97, 88) -0.64  (0.05) -0.45  (0.05) -0.40  (0.05)
TP Day 113 (n=105, 98, 90) -0.67  (0.05) -0.55  (0.05) -0.50  (0.05)
TP Day 141 (n=100, 98, 88) -0.72  (0.05) -0.53  (0.05) -0.46  (0.06)
TP Day 169 (n=95, 95, 85) -0.74  (0.05) -0.59  (0.05) -0.52  (0.06)
TP Day 197 (n=99, 96, 83) -0.78  (0.05) -0.62  (0.06) -0.54  (0.06)
TP Day 225 (n=98, 95, 83) -0.79  (0.06) -0.67  (0.06) -0.56  (0.06)
TP Day 253 (n=96, 91, 84) -0.82  (0.05) -0.65  (0.06) -0.63  (0.06)
TP Day 281 (n=90, 93, 81) -0.82  (0.06) -0.65  (0.06) -0.62  (0.06)
TP Day 309 (n=89, 88, 82) -0.81  (0.06) -0.67  (0.06) -0.66  (0.06)
TP Day 337 (n=88, 85, 80) -0.84  (0.06) -0.70  (0.06) -0.70  (0.06)
TP Day 365 (n=90, 82, 77) -0.87  (0.06) -0.73  (0.06) -0.72  (0.06)
WP Day 29 (n=70, 55, 55) -0.85  (0.06) -0.67  (0.07) -0.63  (0.07)
WP Day 57 (n=66, 53, 54) -0.67  (0.07) -0.58  (0.08) -0.39  (0.08)
WP Day 85 (n=65, 45, 46) -0.54  (0.08) -0.48  (0.09) -0.37  (0.09)
WP Day 169 (n=34, 28, 26) -0.52  (0.10) -0.49  (0.11) -0.33  (0.12)
9.Secondary Outcome
Title Adjusted Mean Change From Baseline at Months 6, 12, and 18 in Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores of Short Form-36 (SF-36)
Hide Description TP=treatment period; WP=withdrawal period. The SF-36 is a 36-item self-administered questionnaire developed to assess health-related quality of life (QOL) and comprises 8 domains, including 4 physical (physical health, bodily pain, physical functioning and physical role limitations) and 4 mental (mental health, vitality, social functioning, and emotional role limitation) subscales. Responses are used to derive physical and mental component summary scores, ranging from 0 to 100, with higher scores indicating better QOL (0=Poorest Health; 100=Best Health). Mean change from baseline=postbaseline value-baseline value; a higher value signifies improvement.
Time Frame Randomization to Months 6, 12, and 18
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. n=number evaluable
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:

Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period

Abatacept: Injection, subcutaneous, 125 mg by syringe, once weekly, 12 months

Methotrexate: Tablets, oral, 2.5 mg, once weekly, 12 months

Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period

Abatacept: Injection, subcutaneous, 125 mg by syringe, once weekly, 12 months

Methotrexate placebo: Tablets, oral, to match 2.5-mg tablet, once weekly, 12 months

Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period

Methotrexate: Tablets, oral, 2.5 mg, once weekly, 12 months

Abatacept placebo: Injection, subcutaneous, to match 125 mg by syringe, once weekly, 12 months

Overall Number of Participants Analyzed 119 116 116
Mean (Standard Error)
Unit of Measure: Units on a scale
PCS score TP Day 169 (n=106, 95, 96) 11.68  (0.82) 9.16  (0.86) 7.47  (0.85)
PCS score TP Day 365 (n=94, 88, 91) 13.91  (0.93) 10.23  (0.97) 10.92  (0.95)
PCS score WP Day 169 (n=48, 36, 37) 6.16  (1.45) 4.59  (1.65) 6.27  (1.63)
MCS score TP Day 169 (n=106, 95, 96) 6.11  (0.92) 3.99  (0.97) 4.69  (0.95)
MCS score TP Day 365 (n=94, 88, 91) 7.67  (1.04) 5.48  (1.08) 7.23  (1.06)
MCS score WP Day 169 (n=48, 36, 37) 2.75  (1.44) 4.36  (1.64) 2.23  (1.63)
10.Secondary Outcome
Title Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI)
Hide Description TP=treatment period; WP=withdrawal period. Change from Baseline=Postbaseline-baseline value. MRI was used to assess joint damage progression at Months 6, 12, and 18. If >20% of joints with a missing score for a parameter (erosion, osteitis, and synovitis), the MRI score of each parameter was considered missing. If ≤20% of joints had a missing score for a parameter, the MRI score for that parameter from the missing joints was carried forward from the previous MRI assessment, or carried backward from the next MRI assessment, if missing score occurred at baseline. MRI total score ranged from 0 (best outcome) to 4 (worst outcome). A gadolinium-enhanced MRI of the dominant hand-wrist was performed on all randomized patients at 5 points. The hand/wrist assessed to have more synovitis was selected initially and used for all subsequent evaluations. The MRI examination was standardized to ensure sufficient image quality for the evaluation of radiographic progression of rheumatoid arthritis.
Time Frame Randomization to Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. n=the number of patients with both baseline and postbaseline measurements.
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:

Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period

Abatacept: Injection, subcutaneous, 125 mg by syringe, once weekly, 12 months

Methotrexate: Tablets, oral, 2.5 mg, once weekly, 12 months

Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period

Abatacept: Injection, subcutaneous, 125 mg by syringe, once weekly, 12 months

Methotrexate placebo: Tablets, oral, to match 2.5-mg tablet, once weekly, 12 months

Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period

Methotrexate: Tablets, oral, 2.5 mg, once weekly, 12 months

Abatacept placebo: Injection, subcutaneous, to match 125 mg by syringe, once weekly, 12 months

Overall Number of Participants Analyzed 119 116 116
Mean (Standard Error)
Unit of Measure: Units on a scale
Osteitis TP Day 169 (n=93, 94, 89) -2.03  (0.47) -1.13  (0.47) -0.73  (0.48)
Osteitis TP Day 365 (n=83, 74, 78) -2.32  (0.46) -1.30  (0.46) -0.90  (0.46)
Osteitis WP Day 169 (n=31, 30, 25) -1.94  (0.88) 0.98  (0.89) -0.33  (0.96)
Erosion TP Day 169 (n=93, 94, 89) 0.26  (0.28) 1.15  (0.28) 1.15  (0.28)
Erosion TP Day 365 (n=83, 74, 78) 0.34  (0.35) 1.57  (0.36) 1.56  (0.36)
Erosion WP Day 169 (n=31, 30, 25) 0.20  (0.47) 2.16  (0.48) 1.89  (0.50)
Synovitis TP Day 169 (n=93, 94, 89) -1.82  (0.21) -0.93  (0.21) -0.78  (0.21)
Synovitis TP Day 365 (n=83, 74, 78) -2.38  (0.29) -1.36  (0.30) -0.77  (0.30)
Synovitis WP Day 169 (n=31, 30, 25)) -1.71  (0.45) -0.95  (0.45) -0.71  (0.49)
11.Secondary Outcome
Title Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to SAEs, Related Adverse Events (AEs), and Discontinuations Due to AEs During the Treatment Period
Hide Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug.
Time Frame Day 1 to up to 56 days following the last dosing day (Day 365); all deaths during study period, including those that occurred >56 days after last dose in Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:
Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Overall Number of Participants Analyzed 119 116 116
Measure Type: Number
Unit of Measure: Participants
Deaths 0 0 2
SAEs 8 14 9
Related SAEs 3 3 1
Discontinuations due to SAEs 2 5 3
Related AEs 53 48 51
Discontinuations due to AEs 4 8 5
12.Secondary Outcome
Title Adverse Events (AEs) of Interest During the Treatment Period
Hide Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug. AEs of special interest are events potentially associated with the drug or disease under study.
Time Frame Day 1 to 56 days following last dosing day (Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:
Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Overall Number of Participants Analyzed 119 116 116
Measure Type: Number
Unit of Measure: Participants
Infections 68 64 69
Malignancy 1 2 1
Autoimmune disorders (prespecified) 1 2 3
Local injection site reactions (prespecified) 2 0 0
13.Secondary Outcome
Title Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period
Hide Description Lower limit of normal (LLN); Upper limit of normal (ULN); Pretreatment (preRX). Criteria for marked abnormality: Platelet count (*10^9 c/µL) <0.67*LLN or >1.5*ULN, or if preRX<LLN, use 0.5*preRX and <100,000/mm^3; potassium, serum (mEq) <0.9*LLN or >1.1*ULN, or if preRX <LLN, use <0.9*preRX or >ULN if preRX>ULN, use >1.1*preRX or <LLN; blood urea nitrogen (mg/dL) >2*preRX; creatinine (mg/dL) >1.5*preRX; ALT (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; AST (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; ALP (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; G-glutamyl transferase U/L) >2*ULN, or if preRX>ULN, use >3*preRX; glucose, fasting (mg/dL) <0.8*LLN or >1.5*ULN, or if preRX<LLN use <0.8*preRX or >ULN if preRX >ULN, use >2.0*preRX or OR <LLN; glucose, serum (mg/dL) <65 or >220; uric acid (mg/dL)>1.5*ULN, or if preRX, use >2*preRX; albumin (g/dL) <0.9*LLN, or if preRX<LLN, use <0.75*preRX; hemoglobin (g/dL)>3 decrease from preRX; hematocrit (%) < 0.75*preRX.
Time Frame Day 1 up to 56 days following the last dosing day in the Treatment Period (Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. n=number evaluable
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:
Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Overall Number of Participants Analyzed 119 116 116
Measure Type: Number
Unit of Measure: Participants
Platelet count (high) (n=119, 116, 115) 2 0 0
Potassium, serum (low) 1 1 1
Blood urea nitrogen (high) 4 1 2
Creatinine (high) 2 1 3
Alanine aminotransferase (ALT)(high) 3 0 2
Aspartate aminotransferase (AST)(high) 2 0 1
G-glutamyl transferase (GGT) (high) 3 1 1
Glucose, fasting (low) (n=78, 72, 75) 2 0 2
Glucose, fasting (high) (n=78, 72, 75) 1 2 1
Glucose, serum (low) (n=84, 78, 75) 5 6 2
Glucose, serum (high) (n=84, 78, 75) 1 4 3
Uric acid (high) 0 1 0
Albumin (low) 1 1 4
Hemoglobin (low) (n=119, 116, 115) 0 2 0
Hematocrit (low) (n=119, 116, 115) 0 2 0
14.Secondary Outcome
Title Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time During Withdrawal Period- Treated Participants in Remission at Month 12
Hide Description WP=withdrawal period. Remission defined as DAS28-CRP<2.6. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.). Percentage= number of participants with remission divided by number of participants who were analyzed (all treated participants who were in remission at end of treatment period and entered the Withdrawal Period)
Time Frame End of Treatment Period (Month 12) to End of Withdrawal Period (Month 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Treated participants who were in remission at Month 12 (DAS28-CRP<2.6) and entered the Withdrawal Period were analyzed.( N=number of participants analyzed).
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:
Participants received abatacept, 125 mg subcutaneously, plus methotrexate (MTX), 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Overall Number of Participants Analyzed 73 50 53
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
WP Day 29
73.3
(65.46 to 85.23)
72.0
(59.55 to 84.45)
54.7
(41.32 to 68.12)
WP Day 57
58.9
(47.62 to 70.19)
56.0
(42.24 to 69.76)
32.1
(19.51 to 44.64)
WP Day 85
42.5
(31.13 to 53.80)
40.0
(26.42 to 53.58)
35.8
(22.94 to 48.76)
WP Day 169
26.0
(15.96 to 36.09)
30.0
(17.30 to 42.70)
17.0
(6.87 to 27.09)
WP Day 253
20.5
(11.28 to 29.82)
22.0
(10.52 to 33.48)
20.8
(9.84 to 31.67)
WP Day 365
12.3
(4.79 to 19.87)
14.0
(4.38 to 23.62)
11.3
(2.79 to 19.85)
15.Secondary Outcome
Title Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period
Hide Description TP=treatment period; WP=withdrawal period. SDAI-defined remission= ≤3.3. The SDAI is the simple linear sum of 5 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) (based on a 28-joint assessment); patient's and physician's global assessments of disease activity (assessed on 0-10 cm visual analog scale, on which higher scores=greater affection due to disease activity); and C-reactive protein level (mg/dL). SDAI total score=0-86. SDAI <=3.3 indicates disease remission, >3.4 to 11=low disease activity, >11 to 26=moderate disease activity, and >26=high disease activity. TJC is assessed and recorded at each visit, with no swelling=0, swelling=1. SJC is assessed through identification of joints that are painful under pressure or to passive motion. TJC is recorded on the joint assessment form at each visit, with no tenderness =0, tenderness = 1. Higher score indicates greater affection due to disease activity. Percent=number with remission/number evaluated (ITT)
Time Frame Randomization to Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis population: Included all randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. Participants were grouped according to the treatment regimen to which they were randomized.N= number evaluated.
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:
Participants received abatacept, 125 mg subcutaneously, plus methotrexate (MTX), 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Overall Number of Participants Analyzed 119 116 116
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
TP Day 29
4.2
(1.38 to 9.53)
3.4
(0.95 to 8.59)
1.7
(0.21 to 6.09)
TP Day 57
9.2
(4.71 to 15.94)
6.0
(2.46 to 12.04)
1.7
(0.21 to 6.09)
TP Day 85
17.6
(10.80 to 24.50)
8.6
(3.51 to 13.73)
6.0
(1.70 to 10.37)
TP Day 113
23.5
(15.91 to 31.15)
17.2
(10.37 to 24.12)
7.8
(2.89 to 12.63)
TP Day 141
31.9
(23.56 to 40.31)
23.3
(15.59 to 30.97)
10.3
(4.80 to 15.89)
TP Day 169
31.1
(22.78 to 39.41)
20.7
(13.32 to 28.06)
11.2
(5.47 to 16.95)
TP Day 197
33.6
(25.13 to 42.10)
21.6
(14.07 to 29.03)
12.9
(6.82 to 19.04)
TP Day 225
38.7
(29.91 to 47.40)
25.9
(17.89 to 33.83)
14.7
(8.22 to 21.09)
TP Day 253
37.8
(29.10 to 46.53)
25.0
(17.12 to 32.88)
13.8
(7.52 to 20.07)
TP Day 281
37.8
(29.10 to 46.53)
26.7
(18.67 to 34.78)
18.1
(11.10 to 25.11)
TP Day 309
40.3
(31.52 to 49.15)
26.7
(18.67 to 34.78)
19.0
(11.83 to 26.10)
TP Day 337
41.2
(32.33 to 50.02)
31.0
(22.62 to 39.45)
19.0
(11.83 to 26.10)
TP Day 365
42.0
(33.15 to 50.89)
29.3
(21.03 to 37.59)
25.0
(17.12 to 32.88)
WP Day 29
38.7
(29.91 to 47.40)
26.7
(18.67 to 34.78)
14.7
(8.22 to 21.09)
WP Day 57
26.9
(18.92 to 34.86)
20.7
(13.32 to 28.06)
10.3
(4.80 to 15.89)
WP Day 85
21.0
(13.69 to 28.33)
15.5
(8.93 to 22.11)
14.7
(8.22 to 21.09)
WP Day 169
11.8
(5.98 to 17.55)
9.5
(4.15 to 14.81)
6.9
(2.29 to 11.51)
WP Day 253
11.8
(5.98 to 17.55)
9.5
(4.15 to 14.81)
7.8
(2.89 to 12.63)
WP Day 365
6.7
(2.22 to 11.22)
4.3
(0.61 to 8.01)
4.3
(0.61 to 8.01)
16.Secondary Outcome
Title Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) and Discontinuations Due to AEs During the Full Study (All Periods)
Hide Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Includes data up to last active dose date +56 days if the participant discontinued the Treatment Period or did not enter the Withdrawal Period, up to the day of discontinuation in the Withdrawal Period for participants discontinuing the Withdrawal Period without entering the Re-exposure Period (RP), up to Day 729 visit (Month 24) for participants who complete the Withdrawal Period, and up to 56 days post last active dose in Re-exposure Period for participants entering the Re-exposure Period.
Time Frame Day 1 to 56 days post last dose in the study, up to Month 30
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Hide Analysis Population Description
All randomized participants who received at least 1 dose of study medication were analyzed.
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:
Participants received abatacept, 125 mg subcutaneously, plus methotrexate (MTX), 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Overall Number of Participants Analyzed 119 116 116
Measure Type: Number
Unit of Measure: participants
Death 0 0 2
SAE 11 15 15
Discontinued Due to AE 4 8 7
17.Secondary Outcome
Title Adverse Events (AEs) of Interest During the Withdrawal Period
Hide Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. AEs of special interest are events potentially associated with the drug or disease under study. Includes events with an onset date on or after 57 days post last dosing day (active abatacept or active MTX whichever is the later) in the Treatment Period and up to end of Withdrawal Period. Treatment groups represent treatment received during the Treatment Period.
Time Frame Last dose in TP + 57 days, up to Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period and entered the Withdrawal Period. Treatment groups represent treatment during the TP.
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:
Participants received abatacept, 125 mg subcutaneously, plus methotrexate (MTX), 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Overall Number of Participants Analyzed 84 66 75
Measure Type: Number
Unit of Measure: participants
Infections 8 6 10
Malignancy 1 0 1
Autoimmune disorders (prespecified) 0 0 1
Local injection site reactions(prespecified) 0 0 0
18.Secondary Outcome
Title Adverse Events (AEs) of Interest During the Re-exposure Period
Hide Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. AEs of special interest are events potentially associated with the drug or disease under study. Includes data up to 56 days post the last dosing day (active abatacept or active MTX, whichever is the later) in the Re-exposure Period. Treatment groups represent Treatment received during Treatment Period.
Time Frame First dose in Re-exposure period up to last dose of Re-exposure Period + 56 days
Hide Outcome Measure Data
Hide Analysis Population Description
Includes data up to 56 days post the last dosing day (active abatacept or active MTX, whichever is the later) in the Re-exposure Period. Treatment groups represent Treatment received during Treatment Period.
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:
Participants received abatacept, 125 mg subcutaneously, plus methotrexate (MTX), 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Overall Number of Participants Analyzed 55 48 43
Measure Type: Number
Unit of Measure: participants
Infections 17 8 12
Malignancy 0 0 0
Autoimmune Disorders (prespecified) 0 0 0
Local Injection site reactions (prespecified) 0 0 0
19.Secondary Outcome
Title Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Withdrawal Period
Hide Description LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Criteria for marked abnormality on laboratory test results: Platelet count (*10^9 c/µL) <0.67*LLN or >1.5*ULN, or if preRX<LLN, use 0.5*preRX and <100,000/mm^3; potassium, serum (mEq) <0.9*LLN or >1.1*ULN, or if preRX <LLN, use <0.9*preRX or >ULN if preRX>ULN, use >1.1*preRX or <LLN; blood urea nitrogen (mg/dL) >2*preRX; creatinine (mg/dL) >1.5*preRX; ALT (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; AST (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; ALP (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; G-glutamyl transferase (GGT) (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; glucose, fasting (mg/dL) <0.8*LLN or >1.5*ULN, or if preRX<LLN use <0.8*preRX or >ULN if preRX >ULN, use >2.0*preRX or OR <LLN; glucose, serum (mg/dL) <65 or >220; uric acid (mg/dL)>1.5*ULN, or if preRX, use >2*preRX; albumin (g/dL) <0.9*LLN, or if preRX<LLN, use <0.75*preRX; hemoglobin (g/dL)>3 decrease from preRX; hematocrit (%) < 0.75*preRX.
Time Frame Last dose in TP + 57 days, up to Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug in the Treatment Period, entered the Withdrawal Period, and had values available. n=number evaluable
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:
Participants received abatacept, 125 mg subcutaneously, plus methotrexate (MTX), 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Overall Number of Participants Analyzed 60 52 48
Measure Type: Number
Unit of Measure: participants
Hemoglobin Low (n=60, 52, 48) 1 2 0
Creatinine High (n=60, 52, 48) 1 2 2
Alanine aminotransferase (ALT) High (n=60, 52, 48) 1 0 0
GGT High (n=60, 52, 48) 1 0 0
Fasting Glucose High (30, 28, 25) 0 2 1
Glucose Low (n=36,31,27) 5 3 0
Glucose High (n=36, 31, 27) 0 1 1
20.Secondary Outcome
Title Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period
Hide Description LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Criteria for marked abnormality on laboratory test results: Platelet count (*10^9 c/µL) <0.67*LLN or >1.5*ULN, or if preRX<LLN, use 0.5*preRX and <100,000/mm^3; potassium, serum (mEq) <0.9*LLN or >1.1*ULN, or if preRX <LLN, use <0.9*preRX or >ULN if preRX>ULN, use >1.1*preRX or <LLN; blood urea nitrogen (mg/dL) >2*preRX; creatinine (mg/dL) >1.5*preRX; ALT (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; AST (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; ALP (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; G-glutamyl transferase U/L) >2*ULN, or if preRX>ULN, use >3*preRX; glucose, fasting (mg/dL) <0.8*LLN or >1.5*ULN, or if preRX<LLN use <0.8*preRX or >ULN if preRX >ULN, use >2.0*preRX or OR <LLN; glucose, serum (mg/dL) <65 or >220; uric acid (mg/dL)>1.5*ULN, or if preRX, use >2*preRX; albumin (g/dL) <0.9*LLN, or if preRX<LLN, use <0.75*preRX; hemoglobin (g/dL)>3 decrease from preRX; hematocrit (%) < 0.75*preRX.
Time Frame Start of re-exposure period to 56 days post last dose, up to Month 30
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants entering the Re-exposure Period and having measurements available were analyzed. n=evaluable. Treatment groups represent Treatment received during Treatment Period.
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description:
Participants received abatacept, 125 mg subcutaneously, plus methotrexate (MTX), 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Overall Number of Participants Analyzed 55 48 43
Measure Type: Number
Unit of Measure: participants
Hematocrit Low (n=55,47,43) 0 1 0
Hemoglobin Low (n=55,48, 43) 0 2 0
Creatinine High (n=55, 48, 43) 0 1 0
ALT High (n=55, 48, 43) 2 0 2
ALP High (n=55, 48, 43) 1 0 0
AST High (n=55, 48, 43) 2 0 1
GGT High (n=55, 48, 43) 2 0 1
Fasting Glucose Low (n=33, 32, 28) 1 0 0
Fasting Glucose High (n=33, 32, 28) 0 2 1
Glucose Low (n=27,24,18) 0 2 0
Glucose High (n=27,24,18) 0 0 0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Hide Arm/Group Description Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period. Participants with a LDAS defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of RA symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC 125 mg/week and MTX. Safety data was collected from Day 1 to 56 days post last dose. Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Participants with a LDAS defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. Participants who experienced a worsening of RA symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. Safety data was collected from Day 1 to 56 days post last dose. Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Participants with a LDAS defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of RA symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. Safety data was collected from Day 1 to 56 days post last dose.
All-Cause Mortality
Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/119 (9.24%)   15/116 (12.93%)   15/116 (12.93%) 
Blood and lymphatic system disorders       
Anaemia  1  0/119 (0.00%)  1/116 (0.86%)  0/116 (0.00%) 
Pancytopenia  1  1/119 (0.84%)  0/116 (0.00%)  0/116 (0.00%) 
Cardiac disorders       
Myocardial infarction  1  0/119 (0.00%)  1/116 (0.86%)  0/116 (0.00%) 
Myocarditis post infection  1  0/119 (0.00%)  1/116 (0.86%)  0/116 (0.00%) 
Gastrointestinal disorders       
Small intestinal obstruction  1  0/119 (0.00%)  0/116 (0.00%)  1/116 (0.86%) 
Incarcerated inguinal hernia  1  0/119 (0.00%)  0/116 (0.00%)  1/116 (0.86%) 
General disorders       
Strangulated hernia  1  0/119 (0.00%)  1/116 (0.86%)  0/116 (0.00%) 
Hepatobiliary disorders       
Cholelithiasis  1  0/119 (0.00%)  0/116 (0.00%)  1/116 (0.86%) 
Cholangitis  1  1/119 (0.84%)  0/116 (0.00%)  0/116 (0.00%) 
Cholecystitis  1  1/119 (0.84%)  0/116 (0.00%)  1/116 (0.86%) 
Infections and infestations       
Urinary tract infection  1  0/119 (0.00%)  0/116 (0.00%)  1/116 (0.86%) 
Herpes zoster  1  0/119 (0.00%)  1/116 (0.86%)  0/116 (0.00%) 
Pneumonia  1  1/119 (0.84%)  1/116 (0.86%)  0/116 (0.00%) 
Viral infection  1  0/119 (0.00%)  1/116 (0.86%)  0/116 (0.00%) 
Abscess limb  1  0/119 (0.00%)  1/116 (0.86%)  0/116 (0.00%) 
Pyelonephritis  1  0/119 (0.00%)  0/116 (0.00%)  1/116 (0.86%) 
Injury, poisoning and procedural complications       
Post procedural complication  1  1/119 (0.84%)  0/116 (0.00%)  0/116 (0.00%) 
Hand fracture  1  0/119 (0.00%)  1/116 (0.86%)  0/116 (0.00%) 
Tendon rupture  1  1/119 (0.84%)  0/116 (0.00%)  0/116 (0.00%) 
Overdose  1  3/119 (2.52%)  1/116 (0.86%)  2/116 (1.72%) 
Investigations       
Hepatic enzyme increased  1  1/119 (0.84%)  0/116 (0.00%)  1/116 (0.86%) 
Transaminases increased  1  1/119 (0.84%)  0/116 (0.00%)  0/116 (0.00%) 
Musculoskeletal and connective tissue disorders       
Osteoarthritis  1  1/119 (0.84%)  0/116 (0.00%)  0/116 (0.00%) 
Rheumatoid arthritis  1  0/119 (0.00%)  0/116 (0.00%)  1/116 (0.86%) 
Foot deformity  1  0/119 (0.00%)  0/116 (0.00%)  1/116 (0.86%) 
Bursitis  1  0/119 (0.00%)  0/116 (0.00%)  1/116 (0.86%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Invasive ductal breast carcinoma  1  0/119 (0.00%)  0/116 (0.00%)  1/116 (0.86%) 
Uterine cancer  1  0/119 (0.00%)  0/116 (0.00%)  1/116 (0.86%) 
Bowen's disease  1  0/119 (0.00%)  1/116 (0.86%)  0/116 (0.00%) 
Prostate cancer  1  1/119 (0.84%)  0/116 (0.00%)  0/116 (0.00%) 
Colon adenoma  1  0/119 (0.00%)  0/116 (0.00%)  1/116 (0.86%) 
Basal cell carcinoma  1  1/119 (0.84%)  0/116 (0.00%)  0/116 (0.00%) 
Carcinoid tumour pulmonary  1  0/119 (0.00%)  1/116 (0.86%)  0/116 (0.00%) 
Uterine neoplasm  1  0/119 (0.00%)  0/116 (0.00%)  1/116 (0.86%) 
Nervous system disorders       
Carotid artery occlusion  1  0/119 (0.00%)  1/116 (0.86%)  0/116 (0.00%) 
Sciatica  1  0/119 (0.00%)  1/116 (0.86%)  1/116 (0.86%) 
Psychiatric disorders       
Depression  1  0/119 (0.00%)  1/116 (0.86%)  0/116 (0.00%) 
Renal and urinary disorders       
Renal failure  1  0/119 (0.00%)  0/116 (0.00%)  1/116 (0.86%) 
Reproductive system and breast disorders       
Endometrial disorder  1  0/119 (0.00%)  1/116 (0.86%)  0/116 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Respiratory failure  1  0/119 (0.00%)  0/116 (0.00%)  1/116 (0.86%) 
Emphysema  1  0/119 (0.00%)  1/116 (0.86%)  0/116 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Abatacept, 125 mg, Plus Methotrexate Placebo Methotrexate, 2.5 mg, Plus Abatacept Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   81/119 (68.07%)   64/116 (55.17%)   78/116 (67.24%) 
Gastrointestinal disorders       
Gastritis  1  4/119 (3.36%)  1/116 (0.86%)  7/116 (6.03%) 
Nausea  1  18/119 (15.13%)  8/116 (6.90%)  16/116 (13.79%) 
Mouth ulceration  1  6/119 (5.04%)  5/116 (4.31%)  2/116 (1.72%) 
Gastrooesophageal reflux disease  1  6/119 (5.04%)  1/116 (0.86%)  1/116 (0.86%) 
Diarrhoea  1  5/119 (4.20%)  8/116 (6.90%)  4/116 (3.45%) 
Abdominal pain upper  1  5/119 (4.20%)  6/116 (5.17%)  6/116 (5.17%) 
Vomiting  1  6/119 (5.04%)  3/116 (2.59%)  1/116 (0.86%) 
Infections and infestations       
Pharyngitis  1  3/119 (2.52%)  6/116 (5.17%)  7/116 (6.03%) 
Urinary tract infection  1  14/119 (11.76%)  15/116 (12.93%)  15/116 (12.93%) 
Influenza  1  5/119 (4.20%)  9/116 (7.76%)  6/116 (5.17%) 
Sinusitis  1  9/119 (7.56%)  4/116 (3.45%)  2/116 (1.72%) 
Gastroenteritis  1  6/119 (5.04%)  3/116 (2.59%)  8/116 (6.90%) 
Nasopharyngitis  1  28/119 (23.53%)  20/116 (17.24%)  22/116 (18.97%) 
Bronchitis  1  8/119 (6.72%)  6/116 (5.17%)  10/116 (8.62%) 
Upper respiratory tract infection  1  15/119 (12.61%)  15/116 (12.93%)  20/116 (17.24%) 
Nervous system disorders       
Headache  1  8/119 (6.72%)  8/116 (6.90%)  7/116 (6.03%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  4/119 (3.36%)  9/116 (7.76%)  7/116 (6.03%) 
Vascular disorders       
Hypertension  1  4/119 (3.36%)  2/116 (1.72%)  6/116 (5.17%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01142726     History of Changes
Other Study ID Numbers: IM101-226
2010-018674-20 ( EudraCT Number )
First Submitted: June 3, 2010
First Posted: June 11, 2010
Results First Submitted: September 25, 2014
Results First Posted: October 17, 2014
Last Update Posted: January 14, 2016