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Trial record 39 of 137 for:    "Connective Tissue Disease" | "Abatacept"

Abatacept Versus Adalimumab Head-to-Head

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ClinicalTrials.gov Identifier: NCT00929864
Recruitment Status : Completed
First Posted : June 30, 2009
Results First Posted : January 3, 2014
Last Update Posted : February 4, 2014
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Investigator);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: Abatacept
Drug: Adalimumab
Enrollment 869
Recruitment Details 28-October-2009 to 23-November-2012. Study conducted in biologic-naive participants with Rheumatoid Arthritis (RA) who have failed on methotrexate therapy.
Pre-assignment Details 869 enrolled; 648 randomized; 646 randomized and treated. Reasons for not randomized: 4 pregnancy; 23 lost to follow-up; 133 administrative reasons by Sponsor; 4 no longer met study criteria; 7 other; 50 had reasons missing. Two participants randomized/not treated: no longer met study criteria. Randomization stratified by DAS28-CRP>5.1, <=5.1
Arm/Group Title 125 mg Abatacept SC Weekly 40 mg Adalimumab SC Biweekly
Hide Arm/Group Description Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX. Adalimumab 40 mg, biweekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Period Title: Overall Study
Started 318 328
Completed 252 245
Not Completed 66 83
Reason Not Completed
Death             1             1
Adverse Event             11             30
Lack of Efficacy             19             16
Lost to Follow-up             7             12
Withdrawal by Subject             20             9
No longer met criteria             2             1
Poor or non-compliance             3             3
Pregnancy             0             3
Administrative reason by Sponsor             1             1
Non-specified             2             7
Arm/Group Title Abatacept Adalimumab Total
Hide Arm/Group Description Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX. Adalimumab 40 mg, bi-weekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX. Total of all reporting groups
Overall Number of Baseline Participants 318 328 646
Hide Baseline Analysis Population Description
All randomized and treated participants who started the 12 month period.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 318 participants 328 participants 646 participants
51.4  (12.6) 51.0  (12.8) 51.2  (12.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 318 participants 328 participants 646 participants
Female
259
  81.4%
270
  82.3%
529
  81.9%
Male
59
  18.6%
58
  17.7%
117
  18.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 318 participants 328 participants 646 participants
North America 230 235 465
South America 88 93 181
1.Primary Outcome
Title The Proportion of Participants Meeting the American College of Rheumatology (ACR) Criteria of 20% Improvement (ACR20) After 12 Months of Treatment - Intent to Treat Population
Hide Description Proportion(%)=number of participants meeting criteria (n) divided by number of participants who received drug (N). The ACR score indicates degree of improvement in a patient's rheumatoid arthritis (RA), based on guidelines set forth by the ACR and represents a percentage. To qualify a ACR20 score, patient must have >=20% fewer tender joints and >=20% fewer swollen joints and show 20% improvement from baseline in at least 3 of: patient overall assessment of his/her RA, physician global assessment of the patient’s RA, patient self-assessment of pain, patient self-assessment of physical functioning, and results of an erythrocyte sedimentation rate or C-reactive protein (CRP) test (to assess inflammation). Baseline was Day 1. Randomization was stratified using screening Disease Activity Score-28 (DAS28) CRP, a composite of 4 variables: number of tender joints/28, number of swollen joints/28, CRP in mg/L and participant assessment of disease activity with visual analogue scale.
Time Frame Day 1 to Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat (ITT) analysis population was defined as all participants randomized into the study who received at least one dose of study drug. n/N = 206/318 and 208/328 in the abatacept and adalimumab arms, respectively.
Arm/Group Title Abatacept Adalimumab
Hide Arm/Group Description:
Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Adalimumab 40 mg, bi-weekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Overall Number of Participants Analyzed 318 328
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
64.8
(59.5 to 70.0)
63.4
(58.2 to 68.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept, Adalimumab
Comments The null and alternative hypotheses are H0: T – C<= δ vs. Ha:T - C > δ, where T is the treatment effect of abatacept, C is the effect of active control (adalimumab),and δ is non-inferiority margin. Abatacept is defined as δ non-inferior to adalimumab when H0 is rejected. More specifically, if the lower bound of the 95% two-sided confidence interval for C-T is greater than δ,, then that Abatacept is δ non-inferior to adalimumab can be claimed.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Analysis tested for non-inferiority. Abatacept will be considered non-inferior to adalimumab if the upper limit of the 95% two-sided CI of difference in ACR20 response rates between the adalimumab arm and the abatacept arm is smaller than or equal to 12%. Estimate and 95% confidence interval (CI) for difference based on minimum risk weights method with randomization stratification of screening Disease Activity Score-28 (DAS28) c-reactive protein (CRP).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method minimum risk weights method
Comments adjusted for randomization stratification of screening Disease Activity Score-28 (DAS28) c-reactive protein (CRP).
Method of Estimation Estimation Parameter Difference from adalimumab at Day 365
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
-5.6 to 9.2
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Proportion of Participants With Local Injection Site Reactions Adverse Events (Pre-specified) Reported During 12 Month Period - ITT Population
Hide Description n=number of participants with a pre-specified local injection site reaction event, N=number of participants at risk. Proportion (%) = n/N. 12 Months includes data up to 56 days post last dose of the first 12 months Period or start of the first dose of second 12 months period.
Time Frame Day 1 to 12 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis population was defined as all participants randomized into the study who received at least one dose of study drug. n/N = 12/318, 30/328 in abatacept and adalimumab, respectively. CI based on normal approximation.
Arm/Group Title Abatacept Adalimumab
Hide Arm/Group Description:
Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Adalimumab 40 mg, bi-weekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Overall Number of Participants Analyzed 318 328
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
3.8
(1.68 to 5.87)
9.1
(6.03 to 12.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept, Adalimumab
Comments Analysis is p-value of difference in proportions. n=number of participants with event, N=number of participants at risk. Proportion = n/N. In order to maintain the overall type I error rate of 0.05 for testing both the primary non-inferiority hypothesis and the key secondary local injection site reaction (LISR) hypothesis, the LISR hypothesis was tested at the 5% significance level only after the primary non-inferiority hypothesis is established at the 5% level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value -5.37
Confidence Interval (2-Sided) 95%
-9.13 to -1.62
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Incidence Rate of Local Injection Site Reactions (Pre-specified) Reported During 24 Month Period - ITT Population
Hide Description Incidence Rate: (incidence/100 person-years) = number of participants with event * 100 /exposure (person-years) Exposure (person-years) = the sum over all participants of the exposure per participant in the 24 months (censored at the time of first occurrence of AE) expressed in days, divided by 365.25. The 24 Month Period includes data up to 56 days post the last dose in the 24 month period. Poisson distribution used to construct the 95% CIs.
Time Frame Day 1 to Day 729
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population: all participants randomized into the study who received at least one dose of study drug. Participants with a pre-specified local injection site event at 24 Months: 13, 34, in abatacept and adalimumab arms, respectively. 24 Month Exposure=579.21, 532.99, respectively.
Arm/Group Title Abatacept Adalimumab
Hide Arm/Group Description:
Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Adalimumab 40 mg, bi-weekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Overall Number of Participants Analyzed 318 328
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: incidence/100 person years
2.24
(1.20 to 3.84)
6.38
(4.42 to 8.91)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept, Adalimumab
Comments Analysis of incidence rate at 24 months. Point estimate and 95% CI. Poisson distribution was used to construct the 95% CIs.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from adalimumab
Estimated Value -4.13
Confidence Interval (2-Sided) 95%
-6.55 to -1.72
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Proportion of Participants Without Radiographic Progression in Total Score Less Than or Equal to the Smallest Detectable Change (SDC) From Baseline to Months 12 and 24 Using Modified Van Der Heijde Total Sharp Score (mSvdHS) - ITT Population
Hide Description Plain radiographs of hands and feet taken at baseline (BL), Day 365, and Day 729. BL and Day 365 radiographs were re-read concurrent with Day 729 films by readers blinded to sequence and treatment (a second pre-specified reading campaign). SDC defined as amount of change for which anything smaller could not be reliably distinguished from random error in measurement of simultaneously read films. Non-progression defined: change from BL (Day 1, prior to dosing) in total score less than, equal to (<=) SDC(2.2). Proportion n/m (%)=number meeting criteria (n); number analyzed (m). SDC calculated as SD/sqrt(2)*1.96/sqrt(2)with standard deviation (SD) of paired differences of change from BL in total score between 2 readers; squared root(sqrt). mSvdHS=summary of erosion severity in 32 hand and 12 foot joints. Hand joints scored 0 to 5; foot joints 0 to 10 with 0=no erosion and higher numbers indicating greater erosion severity. BL: radiographic data within 14 days or less of first dose.
Time Frame Baseline to Day 729
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population: all subjects randomized into the study who received at least one dose of study drug. Number analyzed: m=number of ITT participants with both BL and post-BL total score: Day 365: m=295, 297;Day 729 m=257 and 260, in abatacept and adalimumab arms, respectively. n=number without progression. CI based on normal approximation.
Arm/Group Title Abatacept Adalimumab
Hide Arm/Group Description:
Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Adalimumab 40 mg, bi-weekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Overall Number of Participants Analyzed 295 297
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Day 365 n=259, 263; m=295, 297
87.8
(84.1 to 91.5)
88.6
(84.9 to 92.2)
Day 729 n=218, 218; m=257, 260
84.8
(80.4 to 89.2)
83.8
(79.4 to 88.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept, Adalimumab
Comments This analysis is for Day 365.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method minimum risk weights method
Comments Adjusted for randomization stratification of screening Disease Activity Score-28 (DAS28) c-reactive protein (CRP).
Method of Estimation Estimation Parameter Difference from adalimumab at Day 365
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-6.5 to 3.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Abatacept, Adalimumab
Comments This analysis is for Day 729.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method minimum risk weights method
Comments Adjusted for randomization stratification of screening Disease Activity Score-28 (DAS28) c-reactive protein (CRP).
Method of Estimation Estimation Parameter Difference from adalimumab at Day 729
Estimated Value 0.9
Confidence Interval (2-Sided) 95%
-5.5 to 7.3
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Incidence Rate of Serious Adverse Events (SAEs), Serious Infections, Pre-specified Opportunistic Infections, and Discontinuation for Any Cause at 12 Months of Treatment - ITT Population
Hide Description Pre-specified opportunistic infections include: pneumonia, tuberculosis, herpes zoster, combined opportunistic infections, all hospitalized infections. Incidence Rate: incidence/100 person-years: numerator was number of unique events within this period (up to 56 days post-last dose of first 12 months or start of first dose of second 12 months); denominator was overall total exposure (person-years) within this period, calculated as sum over all participants of exposure (in days) divided by 365.25. The resulting incidence rate was multiplied by 100 to express rate per 100 person-years. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE is 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.
Time Frame Day 1 to Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat (ITT) analysis population was defined as all subjects randomized into the study who received at least one dose of study drug. Poisson distribution was used to construct the 95% CIs.
Arm/Group Title Abatacept Adalimumab
Hide Arm/Group Description:
Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Adalimumab 40 mg, bi-weekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Overall Number of Participants Analyzed 318 328
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: incidence/100 person-years
SAE (number with event=32, 30)
11.06
(7.57 to 15.62)
10.26
(6.92 to 14.65)
Serious Infections (number with event=7, 9)
2.32
(0.93 to 4.79)
2.99
(1.37 to 5.68)
Opportunistic infections (number with event=1, 1)
0.33
(0.01 to 1.83)
0.33
(0.01 to 1.85)
Discontinuation (number with event=44, 59)
14.79
(10.74 to 19.85)
20.11
(15.31 to 25.94)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept, Adalimumab
Comments Analysis for incidence rate of SAE at 12 months. Point estimate and 95% CI for treatment difference. Poisson distribution was used to construct the 95% CIs.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from adalimumab
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
-4.51 to 6.11
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Abatacept, Adalimumab
Comments Analysis for incidence rate of Serious Infections and Infestations at 12 months. Point estimate and 95% CI for treatment difference. Poisson distribution was used to construct the 95% CIs.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from adalimumab
Estimated Value -0.67
Confidence Interval (2-Sided) 95%
-3.27 to 1.94
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Abatacept, Adalimumab
Comments Analysis for incidence rate of Opportunistic Infections at 12 months. Point estimate and 95% CI for treatment difference. Poisson distribution was used to construct the 95% CIs.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from adalimumab
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.92 to 0.91
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Abatacept, Adalimumab
Comments Analysis for incidence rate of discontinuation for any cause at 12 months. Point estimate and 95% CI for treatment difference. Poisson distribution was used to construct the 95% CIs.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from adalimumab
Estimated Value -5.32
Confidence Interval (2-Sided) 95%
-12.06 to 1.41
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Incidence Rate of Serious Adverse Events (SAEs), Serious Infections, Pre-specified Opportunistic Infections, and Discontinuation for Any Cause at 24 Months of Treatment - ITT Population
Hide Description Pre-specified opportunistic infections include: pneumonia, tuberculosis, herpes zoster, combined opportunistic infections, and all hospitalized infections. Incidence Rate: incidence/100 person-years: numerator was number of unique events within this period (up to 56 days post the last dose of the 24 Months period); denominator was overall total exposure (person-years) within this period, which was calculated as the sum over all participants of exposure (in days) divided by 365.25. The resulting incidence rate was multiplied by 100 to express the rate per 100 person-years. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE is 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.
Time Frame Day 1 to Day 729
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat (ITT) analysis population was defined as all subjects randomized into the study who received at least one dose of study drug. Poisson distribution was used to construct the 95% CIs.
Arm/Group Title Abatacept Adalimumab
Hide Arm/Group Description:
Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Adalimumab 40 mg, bi-weekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Overall Number of Participants Analyzed 318 328
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: incidence/100 person-years
SAE Incidence Rate (number with event=44, 54)
13.8
(10.04 to 17.63)
16.5
(12.45 to 20.48)
Serious Infections (number with event=12, 19)
3.8
(1.68 to 5.87)
5.8
(3.26 to 8.32)
Opportunistic infections (number with event=2, 5)
0.6
(0.00 to 1.50)
1.5
(0.20 to 2.85)
Discontinuation (number with event=66, 83)
20.8
(16.30 to 25.21)
25.3
(20.60 to 30.01)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept, Adalimumab
Comments Analysis for incidence rate of SAE at 24 months. Point estimate and 95% CI for treatment difference. Poisson distribution was used to construct the 95% CIs.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from adalimumab
Estimated Value -1.91
Confidence Interval (2-Sided) 95%
-5.43 to 1.61
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Abatacept, Adalimumab
Comments Analysis for incidence rate of Serious infections and infestations Adverse Events at 24 months. Point estimate and 95% CI for treatment difference. Poisson distribution was used to construct the 95% CIs.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from adalimumab
Estimated Value -1.24
Confidence Interval (2-Sided) 95%
-3.12 to 0.63
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Abatacept, Adalimumab
Comments Analysis for incidence rate of opportunistic infections at 24 months. Point estimate and 95% CI for treatment difference. Poisson distribution was used to construct the 95% CIs.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method minimum risk weights method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from adalimumab
Estimated Value -0.52
Confidence Interval (2-Sided) 95%
-1.39 to 0.36
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Abatacept, Adalimumab
Comments Analysis for incidence rate of discontinuations (all cause) at 24 months. Point estimate and 95% CI for treatment difference. Poisson distribution was used to construct the 95% CIs.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from adalimumab
Estimated Value -3.10
Confidence Interval (2-Sided) 95%
-7.13 to 0.92
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Proportion of Participants With Induction of Autoantibodies During the 12 Months and 24 Months Periods - ITT Population
Hide Description The induction of autoantibodies was defined as participant’s antinuclear antibodies (ANA) or anti-double stranded deoxyribonucleic acid (dsDNA) converting from a negative status at baseline to a positive status at a post-baseline measurement time point (Day 365 or Day 729). Proportion (%) = n/m, where n=number of participants with positive ANA or dsDNA at a time point and m=number of participants who had negative ANA or dsDNA at baseline. Blood samples were first tested for ANA by indirect fluorescent assay using HEp-2 Cell Line Substrate, and when positive, samples were further tested for anti-dsDNA by indirect fluorescent assay using Crithidia Luciliae Substrate.
Time Frame Day 1 to Day 729
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population was defined as all participants randomized into the study who received at least one dose of study drug; number analyzed was ITT participants with data at each time point and who had negative ANA or dsDNA at baseline (m)
Arm/Group Title Abatacept Adalimumab
Hide Arm/Group Description:
Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Adalimumab 40 mg, bi-weekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Overall Number of Participants Analyzed 318 328
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Day 365 ANA; n=12, 28; m=229, 210
5.2
(2.4 to 8.1)
13.3
(8.7 to 17.9)
Day 365 anti-dsDNA; n=1, 29; m=299, 293
0.3
(0.0 to 1.0)
9.9
(6.5 to 13.3)
Day 729 ANA; n=12, 24; m=190, 163
6.3
(2.9 to 9.8)
14.7
(9.3 to 20.2)
Day 729 anti-dsDNA; n=0, 29; m=248, 237
0.0
(0.0 to 0.0)
12.2
(8.1 to 16.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abatacept, Adalimumab
Comments Analysis for ANA at Day 365. Point estimate and 95% CI for treatment difference.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from adalimumab
Estimated Value -8.1
Confidence Interval (2-Sided) 95%
-13.9 to -2.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Abatacept, Adalimumab
Comments Analysis for ANA at Day 729. Point estimate and 95% CI for treatment difference
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from adalimumab
Estimated Value -8.4
Confidence Interval (2-Sided) 95%
-15.3 to -1.5
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Abatacept, Adalimumab
Comments Analysis for dsDNA at Day 365. Point estimate and 95% CI for treatment difference.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from adalimumab
Estimated Value -9.6
Confidence Interval (2-Sided) 95%
-13.4 to -5.7
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Abatacept, Adalimumab
Comments Analysis for dsDNA at Day 729. Point estimate and 95% CI for treatment difference.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference from adalimumab
Estimated Value -12.2
Confidence Interval (2-Sided) 95%
-16.9 to -7.6
Estimation Comments [Not Specified]
Time Frame Includes data up to 56 days post the last dose in the 24 months period.
Adverse Event Reporting Description Note: One participant in the abatacept arm had an SAE with no preferred term identified. Therefore, there were 44 participants with SAEs reported in the Outcome measure on the Rate of SAEs but since a preferred term was not identified, a total of 43 are identified in the SAEs below.
 
Arm/Group Title Abatacept Adalimumab
Hide Arm/Group Description Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX. Adalimumab 40 mg, bi-weekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
All-Cause Mortality
Abatacept Adalimumab
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Abatacept Adalimumab
Affected / at Risk (%) Affected / at Risk (%)
Total   43/318 (13.52%)   54/328 (16.46%) 
Blood and lymphatic system disorders     
Pancytopenia  1  1/318 (0.31%)  0/328 (0.00%) 
Anaemia  1  0/318 (0.00%)  1/328 (0.30%) 
Cardiac disorders     
Cardiac arrest  1  1/318 (0.31%)  0/328 (0.00%) 
Cardiomyopathy  1  0/318 (0.00%)  1/328 (0.30%) 
Palpitations  1  0/318 (0.00%)  1/328 (0.30%) 
Myocardial infarction  1  1/318 (0.31%)  0/328 (0.00%) 
Acute coronary syndrome  1  0/318 (0.00%)  1/328 (0.30%) 
Coronary artery disease  1  1/318 (0.31%)  0/328 (0.00%) 
Angina unstable  1  1/318 (0.31%)  0/328 (0.00%) 
Tachycardia  1  1/318 (0.31%)  0/328 (0.00%) 
Angina pectoris  1  2/318 (0.63%)  1/328 (0.30%) 
Cardiac failure congestive  1  1/318 (0.31%)  1/328 (0.30%) 
Ear and labyrinth disorders     
Vertigo  1  0/318 (0.00%)  1/328 (0.30%) 
Endocrine disorders     
Goitre  1  0/318 (0.00%)  1/328 (0.30%) 
Gastrointestinal disorders     
Abdominal hernia  1  1/318 (0.31%)  0/328 (0.00%) 
Gastritis  1  1/318 (0.31%)  1/328 (0.30%) 
Lower gastrointestinal haemorrhage  1  1/318 (0.31%)  0/328 (0.00%) 
Diaphragmatic hernia  1  0/318 (0.00%)  1/328 (0.30%) 
Abdominal pain  1  1/318 (0.31%)  1/328 (0.30%) 
Hiatus hernia  1  1/318 (0.31%)  0/328 (0.00%) 
Small intestinal obstruction  1  1/318 (0.31%)  0/328 (0.00%) 
Pancreatitis  1  1/318 (0.31%)  1/328 (0.30%) 
Pancreatitis acute  1  0/318 (0.00%)  1/328 (0.30%) 
General disorders     
Hernia obstructive  1  0/318 (0.00%)  1/328 (0.30%) 
Non-cardiac chest pain  1  1/318 (0.31%)  3/328 (0.91%) 
Drug withdrawal syndrome  1  1/318 (0.31%)  0/328 (0.00%) 
Chest pain  1  2/318 (0.63%)  0/328 (0.00%) 
Hepatobiliary disorders     
Cholelithiasis  1  2/318 (0.63%)  1/328 (0.30%) 
Cholecystitis acute  1  3/318 (0.94%)  0/328 (0.00%) 
Biliary colic  1  1/318 (0.31%)  0/328 (0.00%) 
Cholecystitis  1  1/318 (0.31%)  1/328 (0.30%) 
Cholecystitis chronic  1  0/318 (0.00%)  1/328 (0.30%) 
Infections and infestations     
Helicobacter gastritis  1  1/318 (0.31%)  0/328 (0.00%) 
Diverticulitis  1  0/318 (0.00%)  2/328 (0.61%) 
Gastroenteritis  1  1/318 (0.31%)  1/328 (0.30%) 
Groin abscess  1  0/318 (0.00%)  1/328 (0.30%) 
Cellulitis  1  0/318 (0.00%)  1/328 (0.30%) 
Oral candidiasis  1  1/318 (0.31%)  0/328 (0.00%) 
Clostridial infection  1  0/318 (0.00%)  1/328 (0.30%) 
Pneumonia  1  3/318 (0.94%)  4/328 (1.22%) 
Pulmonary tuberculosis  1  0/318 (0.00%)  1/328 (0.30%) 
Arthritis bacterial  1  0/318 (0.00%)  3/328 (0.91%) 
Bursitis infective staphylococcal  1  0/318 (0.00%)  1/328 (0.30%) 
Peritonsillar abscess  1  1/318 (0.31%)  0/328 (0.00%) 
Abscess limb  1  1/318 (0.31%)  0/328 (0.00%) 
Disseminated tuberculosis  1  0/318 (0.00%)  1/328 (0.30%) 
Histoplasmosis disseminated  1  0/318 (0.00%)  1/328 (0.30%) 
Bronchitis  1  0/318 (0.00%)  1/328 (0.30%) 
Chest wall abscess  1  0/318 (0.00%)  1/328 (0.30%) 
Meningitis  1  0/318 (0.00%)  1/328 (0.30%) 
Pneumonia mycoplasmal  1  1/318 (0.31%)  0/328 (0.00%) 
Soft tissue infection  1  1/318 (0.31%)  0/328 (0.00%) 
Urinary tract infection  1  3/318 (0.94%)  0/328 (0.00%) 
Injury, poisoning and procedural complications     
Animal bite  1  0/318 (0.00%)  1/328 (0.30%) 
Humerus fracture  1  0/318 (0.00%)  1/328 (0.30%) 
Hip fracture  1  0/318 (0.00%)  1/328 (0.30%) 
Investigations     
Human papilloma virus test positive  1  1/318 (0.31%)  0/328 (0.00%) 
Metabolism and nutrition disorders     
Hypoglycaemia  1  0/318 (0.00%)  1/328 (0.30%) 
Musculoskeletal and connective tissue disorders     
Intervertebral disc protrusion  1  0/318 (0.00%)  1/328 (0.30%) 
Muscular weakness  1  1/318 (0.31%)  0/328 (0.00%) 
Cervical spinal stenosis  1  1/318 (0.31%)  1/328 (0.30%) 
Arthritis  1  0/318 (0.00%)  2/328 (0.61%) 
Joint effusion  1  1/318 (0.31%)  0/328 (0.00%) 
Osteoarthritis  1  1/318 (0.31%)  1/328 (0.30%) 
Osteoporotic fracture  1  0/318 (0.00%)  1/328 (0.30%) 
Arthralgia  1  1/318 (0.31%)  0/328 (0.00%) 
Neck pain  1  0/318 (0.00%)  1/328 (0.30%) 
Rotator cuff syndrome  1  2/318 (0.63%)  0/328 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Leukaemia  1  1/318 (0.31%)  0/328 (0.00%) 
Prostate cancer  1  1/318 (0.31%)  0/328 (0.00%) 
Malignant melanoma  1  0/318 (0.00%)  1/328 (0.30%) 
Small cell lung cancer stage unspecified  1  0/318 (0.00%)  1/328 (0.30%) 
Squamous cell carcinoma of skin  1  2/318 (0.63%)  0/328 (0.00%) 
Transitional cell carcinoma  1  0/318 (0.00%)  2/328 (0.61%) 
Squamous cell carcinoma  1  1/318 (0.31%)  0/328 (0.00%) 
Benign pancreatic neoplasm  1  0/318 (0.00%)  1/328 (0.30%) 
Breast cancer  1  0/318 (0.00%)  1/328 (0.30%) 
Lung neoplasm malignant  1  1/318 (0.31%)  0/328 (0.00%) 
Uterine cancer  1  1/318 (0.31%)  0/328 (0.00%) 
Basal cell carcinoma  1  0/318 (0.00%)  2/328 (0.61%) 
Diffuse large B-cell lymphoma  1  1/318 (0.31%)  0/328 (0.00%) 
Nervous system disorders     
Convulsion  1  1/318 (0.31%)  0/328 (0.00%) 
Lacunar infarction  1  1/318 (0.31%)  0/328 (0.00%) 
Syncope  1  1/318 (0.31%)  1/328 (0.30%) 
Transient ischaemic attack  1  0/318 (0.00%)  1/328 (0.30%) 
Lethargy  1  1/318 (0.31%)  0/328 (0.00%) 
Presyncope  1  1/318 (0.31%)  0/328 (0.00%) 
Carotid artery stenosis  1  0/318 (0.00%)  2/328 (0.61%) 
Cerebrovascular accident  1  0/318 (0.00%)  1/328 (0.30%) 
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous  1  0/318 (0.00%)  1/328 (0.30%) 
Psychiatric disorders     
Drug dependence  1  1/318 (0.31%)  0/328 (0.00%) 
Renal and urinary disorders     
Calculus urinary  1  1/318 (0.31%)  0/328 (0.00%) 
Renal failure acute  1  0/318 (0.00%)  1/328 (0.30%) 
Reproductive system and breast disorders     
Endometrial hyperplasia  1  1/318 (0.31%)  0/328 (0.00%) 
Cervical dysplasia  1  1/318 (0.31%)  0/328 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  0/318 (0.00%)  1/328 (0.30%) 
Asthma  1  0/318 (0.00%)  1/328 (0.30%) 
Bronchospasm  1  1/318 (0.31%)  0/328 (0.00%) 
Pleural effusion  1  0/318 (0.00%)  1/328 (0.30%) 
Chronic obstructive pulmonary disease  1  0/318 (0.00%)  1/328 (0.30%) 
Hypoxia  1  0/318 (0.00%)  1/328 (0.30%) 
Pulmonary embolism  1  1/318 (0.31%)  0/328 (0.00%) 
Pulmonary artery thrombosis  1  0/318 (0.00%)  1/328 (0.30%) 
Epistaxis  1  1/318 (0.31%)  0/328 (0.00%) 
Respiratory failure  1  0/318 (0.00%)  1/328 (0.30%) 
Vascular disorders     
Aortic aneurysm  1  1/318 (0.31%)  0/328 (0.00%) 
Peripheral artery aneurysm  1  1/318 (0.31%)  0/328 (0.00%) 
Deep vein thrombosis  1  0/318 (0.00%)  1/328 (0.30%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Abatacept Adalimumab
Affected / at Risk (%) Affected / at Risk (%)
Total   237/318 (74.53%)   232/328 (70.73%) 
Gastrointestinal disorders     
Diarrhoea  1  29/318 (9.12%)  23/328 (7.01%) 
Vomiting  1  11/318 (3.46%)  18/328 (5.49%) 
Nausea  1  26/318 (8.18%)  28/328 (8.54%) 
General disorders     
Fatigue  1  21/318 (6.60%)  20/328 (6.10%) 
Oedema peripheral  1  22/318 (6.92%)  17/328 (5.18%) 
Infections and infestations     
Gastroenteritis  1  16/318 (5.03%)  13/328 (3.96%) 
Nasopharyngitis  1  61/318 (19.18%)  57/328 (17.38%) 
Sinusitis  1  51/318 (16.04%)  37/328 (11.28%) 
Upper respiratory tract infection  1  64/318 (20.13%)  55/328 (16.77%) 
Influenza  1  21/318 (6.60%)  18/328 (5.49%) 
Bronchitis  1  49/318 (15.41%)  43/328 (13.11%) 
Pharyngitis  1  17/318 (5.35%)  20/328 (6.10%) 
Urinary tract infection  1  41/318 (12.89%)  32/328 (9.76%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  39/318 (12.26%)  39/328 (11.89%) 
Arthralgia  1  9/318 (2.83%)  17/328 (5.18%) 
Nervous system disorders     
Headache  1  32/318 (10.06%)  38/328 (11.59%) 
Psychiatric disorders     
Depression  1  17/318 (5.35%)  14/328 (4.27%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  22/318 (6.92%)  27/328 (8.23%) 
Skin and subcutaneous tissue disorders     
Rash  1  13/318 (4.09%)  27/328 (8.23%) 
Vascular disorders     
Hypertension  1  21/318 (6.60%)  25/328 (7.62%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
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: NCT00929864     History of Changes
Other Study ID Numbers: IM101-235
First Submitted: June 29, 2009
First Posted: June 30, 2009
Results First Submitted: November 14, 2013
Results First Posted: January 3, 2014
Last Update Posted: February 4, 2014