Abatacept and Infliximab in Combination With Methotrexate in Subjects With Rheumatoid Arthritis

Sponsor

Bristol-Myers Squibb (Industry)

Overall Status

Completed

CT.gov ID

NCT00095147

Collaborator

(none)

431

Enrollment

Locations

Arms

52.9

Duration (Months)

5.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this clinical research study is to learn if Abatacept or Infliximab in combination with Methotrexate demonstrate a greater reduction in disease activity over placebo.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Abatacept (ABA) + Methotrexate (MTX), double-blind (DB) Drug: Infliximab (INF) + MTX, DB Drug: Placebo (PLA) + MTX, DB Drug: PLA + MTX switched to ABA+ MTX, DB Drug: ABA, open-label (OL)	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

431 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase IIIB, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Comparative Study of Abatacept or Infliximab in Combination With Methotrexate in Controlling Disease Activity in Subjects With Rheumatoid Arthritis Having an Inadequate Clinical Response to Methotrexate

Study Start Date :

Feb 1, 2005

Actual Primary Completion Date :

Jul 1, 2009

Actual Study Completion Date :

Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Abatacept (ABA) + Methotrexate (MTX) (double-blind [DB]) Days 1-365	Drug: Abatacept (ABA) + Methotrexate (MTX), double-blind (DB) Abatacept, intravenous (IV) Solution, Infusion, Depends on participant weight, Monthly, 12 months. Other Names: Orencia
Active Comparator: Infliximab + MTX (DB) Days 1-365	Drug: Infliximab (INF) + MTX, DB Infliximab, IV Solution, Infusion, Depends on participant weight, Every 2 Months, 12 months.
Placebo Comparator: Placebo + MTX (DB) Days 1-197	Drug: Placebo (PLA) + MTX, DB Placebo, IV Solution, Infusion, Depends on participant weight, Monthly, 6 months.
Experimental: Placebo + MTX switched to abatacept + MTX (DB) Participants received placebo plus methotrexate for days 1-197, and abatacept plus methotrexate for days 198-365	Drug: PLA + MTX switched to ABA+ MTX, DB Placebo=IV Solution, Infusion, Depends on participant weight, Monthly, 6 months. Abatacept=IV Solution, Infusion, Depends on participant weight, Monthly, 6 months Other Names: Orencia
Experimental: Abatacept (open-label) Days 365 to 729 All participants receive Active Drug	Drug: ABA, open-label (OL) Abatacept, IV solution, Infusion. Depends on participant weight, Monthly, 12+ months Other Names: Orencia

Outcome Measures

Primary Outcome Measures

DB; Adjusted Mean Change From Baseline to Day 197 in Disease Activity Score (DAS) 28 Score (Erythrocyte Sedimentation Rate [ESR]) For ABA Versus PLA (Last Observation Carried Forward [LOCF] Analysis) [Baseline (Day 1), 6 months (Day 197)]
The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or C-reactive protein (CRP), and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.
OL; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, and AEs Leading to Discontinuation [From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)]
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
OL; Number of Participants With AEs of Special Interest [From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)]
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
OL; Number of Participants With Select Hematologic Laboratory Abnormalities [From Day 366 through end of OL (range from 1.9 months to 42.3 months)]
High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Erythrocytes: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; lymphocytes: <0.750 x 10^3 c/uL/ >7.50 x 10^3 c/uL; monocytes: >2000 mm3; eosinophils: >0.750 x 10^3 c/uL;
OL; Number of Participants With Select Blood Chemistry Laboratory Abnormalities [From Day 366 through end of OL (range from 1.9 months to 42.3 months)]
Low=lower than LLN, High=greater than ULN. LLN/ULN= Alkaline phosphatase (ALP): >2 x ULN; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL
OL; Mean Change From Baseline to Day 365 in Hemoglobin, Total Protein, and Albumin [Baseline (Day 1), Day 365]
Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN
OL; Mean Change From Baseline to Day 365 in Platelets [Baseline (Day 1), Day 365]
Platelets (PLT): <0.67 x LLN, >1.5 x ULN
OL; Mean Change From Baseline to Day 365 in Hematocrit [Baseline (Day 1), Day 365]
Hematocrit: <0.75 x BL
OL; Mean Change From Baseline to Day 365 in White Blood Cells [Baseline (Day 1), Day 365]
Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.
OL; Mean Change From Baseline to Day 365 in Erythrocytes [Baseline (Day 1), Day 365]
Erythrocytes: <0.75 x BL
OL; Mean Change From Baseline to Day 365 in Electrolytes [Baseline (Day 1), Day 365]
Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN
OL; Mean Change From Baseline to Day 365 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid [Baseline (Day 1), Day 365]
Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;
OL; Mean Change From Baseline to Day 365 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase [Baseline (Day 1), Day 365]
alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN
OL; Mean Change From Baseline to Day 729 in Hemoglobin, Total Protein, and Albumin [Baseline (Day 1), Day 729]
Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN
OL; Mean Change From Baseline to Day 729 in Platelets [Baseline (Day 1), Day 729]
Platelets (PLT): <0.67 x LLN, >1.5 x ULN
OL; Mean Change From Baseline to Day 729 in Hematocrit [Baseline (Day 1), Day 729]
Hematocrit: <0.75 x BL
OL; Mean Change From Baseline to Day 729 in White Blood Cells [Baseline (Day 1), Day 729]
Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.
OL; Mean Change From Baseline to Day 729 in Erythrocytes [Baseline (Day 1), Day 729]
Erythrocytes: <0.75 x BL
OL; Mean Change From Baseline to Day 729 in Electrolytes [Baseline (Day 1), Day 729]
Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN
OL; Mean Change From Baseline to Day 729 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid [Baseline (Day 1), Day 729]
Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;
OL; Mean Change From Baseline to Day 729 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase [Baseline (Day 1), Day 729]
alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN
OL; Mean Change From Baseline to Day 1121 in Hemoglobin, Total Protein, and Albumin [Baseline (Day 1), Day 1121]
Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN
OL; Mean Change From Baseline to Day 1121 in Platelets [Baseline (Day 1), Day 1121]
Platelets (PLT): <0.67 x LLN, >1.5 x ULN
OL; Mean Change From Baseline to Day 1121 in Hematocrit [Baseline (Day 1), Day 1121]
Hematocrit: <0.75 x BL
OL; Mean Change From Baseline to Day 1121 in White Blood Cells [Baseline (Day 1), Day 1121]
Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.
OL; Mean Change From Baseline to Day 1121 in Erythrocytes [Baseline (Day 1), Day 1121]
Erythrocytes: <0.75 x BL
OL; Mean Change From Baseline to Day 1121 in Electrolytes [Baseline (Day 1), Day 1121]
Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN
OL; Mean Change From Baseline to Day 1121 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid [Baseline (Day 1), Day 1121]
Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;
OL; Mean Change From Baseline to Day 1121 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase [Baseline (Day 1), Day 1121]
alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN
OL; Mean Change From Baseline to Day 1513 in Hemoglobin, Total Protein, and Albumin [Baseline (Day 1), Day 1513]
Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN
OL; Mean Change From Baseline to Day 1513 in Platelets [Baseline (Day 1), Day 1513]
Platelets (PLT): <0.67 x LLN, >1.5 x ULN
OL; Mean Change From Baseline to Day 1513 in Hematocrit [Baseline (Day 1), Day 1513]
Hematocrit: <0.75 x BL
OL; Mean Change From Baseline to Day 1513 in White Blood Cells [Baseline (Day 1), Day 1513]
Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.
OL; Mean Change From Baseline to Day 1513 in Erythrocytes [Baseline (Day 1), Day 1513]
Erythrocytes: <0.75 x BL
OL; Mean Change From Baseline to Day 1513 in Electrolytes [Baseline (Day 1), Day 1513]
Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN
OL; Mean Change From Baseline to Day 1513 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid [Baseline (Day 1), Day 1513]
Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;
OL; Mean Change From Baseline to Day 1513 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase [Baseline (Day 1), Day 1513]
alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period [Days 365, 729, 1121, and 1513]
Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP), units=mm mercury (Hg)
OL; Mean Heart Rate (HR) During Open Label Period [Days 365, 729, 1121, and 1513]
Heart Rate (HR), units=beats per minute (bpm)
OL; Mean Temperature (T) During Open Label Period [Days 365, 729, 1121, and 1513]
Temperature (T), units=degrees Celcius

Secondary Outcome Measures

DB; Adjusted Mean Change From Baseline to Day 197 in DAS 28 Score (ESR) For INF Versus PLA (LOCF Analysis) [Baseline (Day 1), 6 months (Day 197)]
The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.
DB; DAS 28 (ESR) Area Under The Curve (AUC) Over 12 Months For ABA Versus INF [From Day 1 through Day 365 (12 months)]
The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). Clinically significant response= decrease in DAS28 score of >1.2 from baseline. DAS28 AUC can be calculated from the DAS28 score versus time curve, which provides an assessment of changes in disease activity over time.
DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 197 [DB Day 197]
The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 365 [DB Day 365]
The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis) [Baseline (Day 1), 6 months (Day 197)]
The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis) [Baseline (Day 1), 12 months (Day 365)]
The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
DB; Adjusted Mean Change From Baseline to Day 197 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) [Baseline (Day 1), 6 months (Day 197)]
The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.
DB; Adjusted Mean Change From Baseline to Day 365 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) [Baseline (Day 1), 12 months (Day 365)]
The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.
DB; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) at Day 365 [DB Day 365]
The DAS28 is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= > 5.1, low disease activity= < 3.2, and remission= < 2.6. Clinically significant response= decrease of >1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from baseline [BL]), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: >5.1 or <0.6 change from BL)
DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 197 [DB Day 197]
The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein [CRP]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.
DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 365 [DB Day 365]
The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein [CRP]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.
DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, and AEs Leading to Discontinuation From Day 1 Through Day 197 [From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study]
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 197 [From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study]
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, and AEs Leading to Discontinuation From Day 1 Through Day 365 [From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study]
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, and AEs Leading to Discontinuation From Day 198 Through Day 365 in Participants Receiving Placebo Switched to Abatacept [From Day 198 through Day 365, and up to 56 days after last dose if occurring on-study]
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 365 [From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study]
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
DB; Number of Participants With AEs of Special Interest From Day 198 Through Day 365 in Participants Receiving Placebo Switched to Abatacept [From Day 198 through Day 365, and up to 56 days after last dose if occurring on-study]
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
DB; Number of Participants With Significant Changes in Mean Systolic and Diastolic Blood Pressure During Days 1 Through 197 and Days 1 Through 365 [From Baseline (Day 1) through Day 197, or Day 1 through Day 365, and up to 56 days after last dose if occurring on-study]
Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
DB; Number of Participants With Significant Changes in Mean Heart Rate During Days 1 Through 197 and Days 1 Through 365 [From Baseline (Day 1) through Day 197, or Day 1 through Day 365, and up to 56 days after last dose if occurring on-study]
Heart Rate (HR) was assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
DB; Number of Participants With Significant Changes in Mean Temperature During Days 1 Through 197 and Days 1 Through 365 [From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study]
Temperature (T) was assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197 [From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study]
High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; creatinine: >4 x BL
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365 [From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study]
High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; creatinine: >4 x BL
DB; Number of Participants With Anti-Abatacept Antibodies From Day 1 Through Day 365 (Electrochemiluminescent [ECL] Immunoassay) [Day 1 through day 365]
ECL screened sera for drug-specific antibodies, immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction Category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing.
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365 [Day 1 through day 365]
Infliximab levels were measured using a microplate enzyme-linked immunosorbant assay (ELISA) with infliximab bound to immobilized recombinant tumor necrosis factor (TNF)-alpha. Bound infliximab is detected utilizing a horseradish peroxidase-conjugated anti-human IgG Fc(fragment, crystallizable region)-specific). The enzyme turns over the substrate O-phenlenediamine to a chromogenic product that is measured at 490 nm. The cut-off value was 1.40 ug/mL; this was based on the mean (+ 3 SD) value in serum samples from 40 participants who had never received infliximab.
OL; Mean Change From Baseline Over Time in DAS 28 (ESR) Score [Baseline (Day 1), Day 365, Day 533, Day 729]
The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.
OL; Percentage of Participants With DAS28 (ESR) Remission and Low Disease Activity (LDAS) Over Time [Baseline (Day 1), Day 365, Day 533, Day 729]
The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.
OL; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Over Time [DB Days 365, 533, and 729]
The DAS28 is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= > 5.1, low disease activity= < 3.2, and remission= < 2.6. Clinically significant response= decrease of >1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute <3.2 or >1.2 improvement from baseline [BL]), moderate (absolute 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute >5.1 or <0.6 change from BL)
OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time [DB Day 197, Day 365, Day 533, Day 729]
The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein [CRP]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.
OL; Percentage of Participants Who Achieved Major Clinical Response [Defined from the date of achieving ACR 70 response to 6 months post response]
Major Clinical Response was defined as a continuous ACR 70 for six months.
OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time [OL Days 197, 253, 281, 309, 337, 365, 449, 533, 617, and 729]
The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
OL; Adjusted Mean Change From Baseline to Day 729 in HAQ-DI [Day 1 (Baseline), Day 729]
The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of Rheumatoid Arthritis
At least 3 months prior treatment with Methotrexate (MTX)
At least 10 swollen joints and 12 tender joints and C-Reactive Protein of at least 1 mg/dl
Washout required for other disease modifying anti-rheumatic drugs (DMARDS)

Exclusion Criteria:

participants who have failed more than 3 DMARDs
participants previously treated with an approved biologic drug
History of cancer in the last 5 years
Severe or recurrent bacterial infection
Any previous or current medical conditions that are contraindications to the use of TNF blocking agents
Women of Child Bearing Potential

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Huntsville	Alabama	United States
2	Local Institution	Denver	Colorado	United States
3	Local Institution	Boca Raton	Florida	United States
4	Local Institution	Ft Lauderdale	Florida	United States
5	Local Institution	Largo	Florida	United States
6	Local Institution	Indianapolis	Indiana	United States
7	Local Institution	New Orleans	Louisiana	United States
8	Local Institution	Springfield	Massachusetts	United States
9	Local Institution	Worcester	Massachusetts	United States
10	Local Institution	Flowood	Mississippi	United States
11	Local Institution	Syracuse	New York	United States
12	Local Institution	Charlotte	North Carolina	United States
13	Local Institution	Cincinnati	Ohio	United States
14	Local Institution	Oklahoma City	Oklahoma	United States
15	Local Institution	Tulsa	Oklahoma	United States
16	Local Institution	Bethlehem	Pennsylvania	United States
17	Local Institution	Willow Grove	Pennsylvania	United States
18	Local Institution	Austin	Texas	United States
19	Local Institution	Dallas	Texas	United States
20	Local Institution	Capital Federal	Buenos Aires	Argentina
21	Local Institution	Quilmes	Buenos Aires	Argentina
22	Local Institution	Buenos Aires		Argentina
23	Local Institution	Cordoba		Argentina
24	Local Institution	Tucuman		Argentina
25	Local Institution	Cairns	Queensland	Australia
26	Local Institution	Cotton Tree	Queensland	Australia
27	Local Institution	Clayton	Victoria	Australia
28	Local Institution	Heidelberg	Victoria	Australia
29	Local Institution	Malvern	Victoria	Australia
30	Local Institution	Parkville	Victoria	Australia
31	Local Institution	Perth	Western Australia	Australia
32	Local Institution	Curitiba	Parana	Brazil
33	Local Institution	Recife	Pernambuco	Brazil
34	Local Institution	Porto Alegre	Rio Grande Do Sul	Brazil
35	Local Institution	Rio De Janeiro		Brazil
36	Local Institution	Sao Paulo		Brazil
37	Local Institution	Calgary	Alberta	Canada
38	Local Institution	Edmonton	Alberta	Canada
39	Local Institution	Winnipeg	Manitoba	Canada
40	Local Institution	St. Johns	Newfoundland and Labrador	Canada
41	Local Institution	Hamilton	Ontario	Canada
42	Local Institution	Kitchener	Ontario	Canada
43	Local Institution	Ottawa	Ontario	Canada
44	Local Institution	Montreal	Quebec	Canada
45	Local Institution	Ste-Foy	Quebec	Canada
46	Local Institution	Saskatoon	Saskatchewan	Canada
47	Local Institution	Kitchener		Canada	ON
48	Local Institution	Prague 2		Czech Republic
49	Local Institution	Copenhagen		Denmark
50	Local Institution	Seoul		Korea, Republic of
51	Local Institution	Tijuana	Baja California	Mexico
52	Local Institution	Mexico	Distrito Federal	Mexico
53	Local Institution	Leon	Guanajuato	Mexico
54	Local Institution	Guadalajara	Jalisco	Mexico
55	Local Institution	Monterrey	Nuevo Leon	Mexico
56	Local Institution	San Luis Potosi		Mexico
57	Local Institution	Lima		Peru
58	Local Institution	Poznan		Poland
59	Local Institution	Sopot		Poland
60	Local Institution	Warszawa		Poland
61	Local Institution	Rio Piedras		Puerto Rico
62	Local Institution	Moscow		Russian Federation
63	Local Institution	Muckleneuk	Gauteng	South Africa
64	Local Institution	Berea	Kwa Zulu Natal	South Africa
65	Local Institution	Panorama	Western Cape	South Africa
66	Local Institution	A Coruna		Spain
67	Local Institution	Barcelona		Spain
68	Local Institution	Cordoba		Spain
69	Local Institution	Madrid		Spain
70	Local Institution	Falun		Sweden
71	Local Institution	Linkoping		Sweden
72	Local Institution	Lund		Sweden
73	Local Institution	Stockholm		Sweden
74	Local Institution	Uppsala		Sweden
75	Local Institution	Bern		Switzerland
76	Local Institution	St. Gallen		Switzerland

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Bristol-Myers Squibb

ClinicalTrials.gov Identifier:

NCT00095147

Other Study ID Numbers:

IM101-043

First Posted:

Nov 2, 2004

Last Update Posted:

Mar 24, 2015

Last Verified:

Mar 1, 2015

Additional relevant MeSH terms:

Arthritis

Arthritis, Rheumatoid

Methotrexate

Abatacept

Infliximab

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	748 participants enrolled in this study; 317 participants were not randomized or treated. 384 participants completed the double-blind period; 12 participants did not enter the open-label period.

Arm/Group Title	Abatacept (ABA) + Methotrexate (MTX) [Double-blind (DB)]	Infliximab (INF) + MTX [DB]	Placebo (PLA) + MTX [DB]	PLA Switched to ABA + MTX [DB]	ABA + MTX [Open-label (OL)]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).	All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
Period Title: Double-blind Period 1 (Days 1-197)
STARTED	156	165	110	0	0
COMPLETED	147	152	107	0	0
NOT COMPLETED	9	13	3	0	0
Period Title: Double-blind Period 1 (Days 1-197)
STARTED	147	152	0	107	0
COMPLETED	139	141	0	104	0
NOT COMPLETED	8	11	0	3	0
Period Title: Double-blind Period 1 (Days 1-197)
STARTED	0	0	0	0	372
COMPLETED	0	0	0	0	327
NOT COMPLETED	0	0	0	0	45

Baseline Characteristics

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]	Total
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)	Total of all reporting groups
Overall Participants	156	165	110	431
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.0 (12.5)	49.1 (12.0)	49.4 (11.5)	49.1 (12.0)
Sex: Female, Male (Count of Participants)
Female	130 83.3%	136 82.4%	96 87.3%	362 84%
Male	26 16.7%	29 17.6%	14 12.7%	69 16%
Baseline Disease Activity Score (DAS) 28 (Erythrocyte Sedimentation Rate [ESR]) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	6.9 (1.0)	6.8 (0.9)	6.8 (1.0)	6.8 (1.0)

Outcome Measures

1. Primary Outcome

Title	DB; Adjusted Mean Change From Baseline to Day 197 in Disease Activity Score (DAS) 28 Score (Erythrocyte Sedimentation Rate [ESR]) For ABA Versus PLA (Last Observation Carried Forward [LOCF] Analysis)
Description	The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or C-reactive protein (CRP), and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.
Time Frame	Baseline (Day 1), 6 months (Day 197)

Outcome Measure Data

Analysis Population Description
The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.

Arm/Group Title	ABA + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	150	102
Mean (Standard Error) [units on a scale]	-2.53 (0.12)	-1.48 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABA + MTX [DB], PLA + MTX [DB]
	Comments	The primary analysis was the comparison of abatacept versus placebo for changes from baseline to 6 months (Day 197) in the DAS28. This comparison was done using an analysis of covariance (ANCOVA) model with treatment group as the effect and baseline value as the covariate. A 95% confidence interval was computed for the treatment difference within the framework of the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	adjusted mean change from baseline
	Estimated Value	-1.04
	Confidence Interval	(2-Sided) 95% -1.42 to -0.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	DB; Adjusted Mean Change From Baseline to Day 197 in DAS 28 Score (ESR) For INF Versus PLA (LOCF Analysis)
Description	The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.
Time Frame	Baseline (Day 1), 6 months (Day 197)

Outcome Measure Data

Analysis Population Description
The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.

Arm/Group Title	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	156	102
Mean (Standard Error) [units on a scale]	-2.25 (0.12)	-1.48 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABA + MTX [DB], PLA + MTX [DB]
	Comments	Infliximab versus placebo were compared for changes from baseline to 6 months (Day 197) in the DAS28. This comparison was done using an analysis of covariance (ANCOVA) model with treatment group as the effect and baseline value as the covariate. A 95% confidence interval was computed for the treatment difference within the framework of the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	adjusted mean change from baseline
	Estimated Value	-0.77
	Confidence Interval	(2-Sided) 95% -1.14 to -0.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	DB; DAS 28 (ESR) Area Under The Curve (AUC) Over 12 Months For ABA Versus INF
Description	The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). Clinically significant response= decrease in DAS28 score of >1.2 from baseline. DAS28 AUC can be calculated from the DAS28 score versus time curve, which provides an assessment of changes in disease activity over time.
Time Frame	From Day 1 through Day 365 (12 months)

Outcome Measure Data

Analysis Population Description
The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.

Arm/Group Title	ABA + MTX [DB[	INF + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	150	156
Mean (Standard Deviation) [units on a scale]	1638.6 (395.81)	1657.5 (460.52)

4. Secondary Outcome

Title	DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 197
Description	The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
Time Frame	DB Day 197

Outcome Measure Data

Analysis Population Description
The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	156	165	110
Number [percentage of participants]	61.5 39.4%	58.8 35.6%	40.9 37.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABA + MTX [DB], PLA + MTX [DB]
	Comments	Comparisons were made between ABA and PLA at Day 197 using a continuity corrected Chi-square test. All tests and confidence intervals for treatment comparison were two-sided.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Chi-squared, Corrected
	Comments

Method of Estimation	Estimation Parameter	Estimate of difference from placebo
	Estimated Value	20.6
	Confidence Interval	(2-Sided) 95% 7.7 to 33.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PLA + MTX [DB], PLA + MTX [DB]
	Comments	Comparisons were made between INF and PLA at Day 197 using a continuity corrected Chi-square test. All tests and confidence intervals for treatment comparison were two-sided.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Chi-squared, Corrected
	Comments

Method of Estimation	Estimation Parameter	Estimate of difference from placebo
	Estimated Value	17.9
	Confidence Interval	(2-Sided) 95% 5.1 to 30.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 365
Description	The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
Time Frame	DB Day 365

Outcome Measure Data

Analysis Population Description
The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	156	165	110
Number [percentage of participants]	57.7 37%	52.7 31.9%	57.3 52.1%

6. Secondary Outcome

Title	DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis)
Description	The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
Time Frame	Baseline (Day 1), 6 months (Day 197)

Outcome Measure Data

Analysis Population Description
The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	156	164	109
HAQ-DI	-0.69 (0.05)	-0.61 (0.05)	-0.31 (0.06)
HAQ-DI component: activities	-0.61 (0.06)	-0.54 (0.06)	-0.22 (0.08)
HAQ-DI component: dressing and grooming	-0.69 (0.06)	-0.57 (0.06)	-0.37 (0.07)
HAQ-DI component: eating	-0.79 (0.06)	-0.77 (0.06)	-0.36 (0.08)
HAQ-DI component: grip	-0.73 (0.07)	-0.70 (0.07)	-0.26 (0.08)
HAQ-DI component: hygiene	-0.64 (0.07)	-0.48 (0.07)	-0.26 (0.08)
HAQ-DI component: reach	-0.72 (0.07)	-0.64 (0.07)	-0.30 (0.08)
HAQ-DI component: arising	-0.70 (0.06)	-0.68 (0.06)	-0.39 (0.07)
HAQ-DI component: walking	-0.58 (0.06)	-0.56 (0.06)	-0.23 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABA + MTX [DB], PLA + MTX [DB]
	Comments	Adjusted mean change in HAQ-DI from baseline to 6 months (Day 197) was compared between ABA and PLA. This comparison was done using an analysis of covariance (ANCOVA) model with treatment group as the effect and baseline value as the covariate. A 95% confidence interval was computed for the treatment difference within the framework of the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Difference from placebo
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95% -0.53 to -0.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PLA + MTX [DB], PLA + MTX [DB]
	Comments	Adjusted mean change in HAQ-DI from baseline to 6 months (Day 197) was compared between INF and PLA. This comparison was done using an analysis of covariance (ANCOVA) model with treatment group as the effect and baseline value as the covariate. A 95% confidence interval was computed for the treatment difference within the framework of the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Difference from placebo
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) 95% -0.45 to -0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis)
Description	The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
Time Frame	Baseline (Day 1), 12 months (Day 365)

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) Population: all participants randomized into the study receiving study medication, grouped according to randomization treatment. All participants randomized but never receiving study medication excluded. Although 3 participants in PLA group discontinued before Day 197, 2 of these patients were included in the LOCF analysis.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	156	164	109
HAQ-DI	-0.67 (0.05)	-0.59 (0.05)	-0.56 (0.06)
HAQ-DI component: activities	-0.55 (0.07)	-0.52 (0.07)	-0.55 (0.08)
HAQ-DI component: dressing and grooming	-0.72 (0.06)	-0.60 (0.06)	-0.56 (0.07)
HAQ-DI component: eating	-0.80 (0.06)	-0.73 (0.06)	-0.71 (0.08)
HAQ-DI component: grip	-0.77 (0.07)	-0.64 (0.07)	-0.56 (0.08)
HAQ-DI component: hygiene	-0.53 (0.07)	-0.45 (0.07)	-0.42 (0.09)
HAQ-DI component: reach	-0.77 (0.07)	-0.66 (0.07)	-0.53 (0.08)
HAQ-DI component: arising	-0.68 (0.06)	-0.64 (0.06)	-0.61 (0.07)
HAQ-DI component: walking	-0.54 (0.06)	-0.55 (0.06)	-0.47 (0.07)

8. Secondary Outcome

Title	DB; Adjusted Mean Change From Baseline to Day 197 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)
Description	The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.
Time Frame	Baseline (Day 1), 6 months (Day 197)

Outcome Measure Data

Analysis Population Description
ITT population, all participants randomized into the study receiving study medication. Participants grouped according to the treatment to which they were randomized. All randomized participants who never received study medication were excluded. SF-36 component scores were not presented in tabular form.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	154	163	109
SF-36 Physical Component Summary	8.36 (0.69)	7.66 (0.67)	4.34 (0.82)
SF-36 Mental Component Summary	5.14 (0.79)	4.32 (0.76)	1.64 (0.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABA + MTX [DB], PLA + MTX [DB]
	Comments	Adjusted mean change in SF-36 physical component summary from baseline to 6 months (Day 197) was compared between ABA and PLA. This comparison was done using an analysis of covariance (ANCOVA) model with treatment group as the effect and baseline value as the covariate. A 95% confidence interval was computed for the treatment difference within the framework of the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Difference from placebo (PCS)
	Estimated Value	4.02
	Confidence Interval	(2-Sided) 95% 1.92 to 6.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ABA + MTX [DB], PLA + MTX [DB]
	Comments	Adjusted mean change in SF-36 mental component summary from baseline to 6 months (Day 197) was compared between ABA and PLA. This comparison was done using an analysis of covariance (ANCOVA) model with treatment group as the effect and baseline value as the covariate. A 95% confidence interval was computed for the treatment difference within the framework of the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Difference from placebo (MCS)
	Estimated Value	3.51
	Confidence Interval	(2-Sided) 95% 1.10 to 5.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PLA + MTX [DB], PLA + MTX [DB]
	Comments	Adjusted mean change in SF-36 physical component summary from baseline to 6 months (Day 197) was compared between INF and PLA. This comparison was done using an analysis of covariance (ANCOVA) model with treatment group as the effect and baseline value as the covariate. A 95% confidence interval was computed for the treatment difference within the framework of the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Difference from placebo (PCS)
	Estimated Value	3.32
	Confidence Interval	(2-Sided) 95% 1.25 to 5.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PLA + MTX [DB], PLA + MTX [DB]
	Comments	Adjusted mean change in SF-36 mental component summary from baseline to 6 months (Day 197) was compared between INF and PLA. This comparison was done using an analysis of covariance (ANCOVA) model with treatment group as the effect and baseline value as the covariate. A 95% confidence interval was computed for the treatment difference within the framework of the ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.027
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Difference from placebo (MCS)
	Estimated Value	2.68
	Confidence Interval	(2-Sided) 95% 0.31 to 5.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	DB; Adjusted Mean Change From Baseline to Day 365 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)
Description	The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.
Time Frame	Baseline (Day 1), 12 months (Day 365)

Outcome Measure Data

Analysis Population Description
ITT Population: all participants randomized into the study receiving study medication, grouped according to randomization treatment. Although 3 participants in PLA group discontinued before Day 197, 2 of these patients were included in the LOCF analysis. SF-36 component scores were not presented in tabular form.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	154	163	109
SF-36 Physical Component Summary	9.52 (0.70)	7.59 (0.68)	8.00 (0.83)
SF-36 Mental Component Summary	5.96 (0.81)	4.03 (0.79)	5.85 (0.97)

10. Secondary Outcome

Title	DB; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) at Day 365
Description	The DAS28 is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= > 5.1, low disease activity= < 3.2, and remission= < 2.6. Clinically significant response= decrease of >1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from baseline [BL]), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: >5.1 or <0.6 change from BL)
Time Frame	DB Day 365

Outcome Measure Data

Analysis Population Description
The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	150	157	102
No response	27.3 17.5%	36.3 22%	23.5 21.4%
Moderate response	40.7 26.1%	45.2 27.4%	49.0 44.5%
Good response	32.0 20.5%	18.5 11.2%	27.5 25%

11. Secondary Outcome

Title	DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 197
Description	The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein [CRP]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.
Time Frame	DB Day 197

Outcome Measure Data

Analysis Population Description
The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	156	165	110
Day 197, ACR 20	66.7 42.8%	59.4 36%	41.8 38%
Day 197, ACR 50	40.4 25.9%	37.0 22.4%	20.0 18.2%
Day 197, ACR 70	20.5 13.1%	24.2 14.7%	9.1 8.3%

12. Secondary Outcome

Title	DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 365
Description	The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein [CRP]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.
Time Frame	DB Day 365

Outcome Measure Data

Analysis Population Description
The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	156	165	110
Day 365, ACR 20	72.4 46.4%	55.8 33.8%	68.2 62%
Day 365, ACR 50	45.5 29.2%	36.4 22.1%	50.9 46.3%
Day 365, ACR 70	26.3 16.9%	20.6 12.5%	29.1 26.5%

13. Secondary Outcome

Title	DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, and AEs Leading to Discontinuation From Day 1 Through Day 197
Description	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame	From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study

Outcome Measure Data

Analysis Population Description
The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	156	165	110
Deaths	1 0.6%	1 0.6%	0 0%
SAEs	8 5.1%	19 11.5%	13 11.8%
Related SAEs	3 1.9%	8 4.8%	3 2.7%
SAEs Leading to Discontinuation	2 1.3%	4 2.4%	0 0%
AEs	129 82.7%	140 84.8%	92 83.6%
Related AEs	64 41%	74 44.8%	46 41.8%
AEs Leading to discontinuation	3 1.9%	8 4.8%	1 0.9%

14. Secondary Outcome

Title	DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 197
Description	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
Time Frame	From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study

Outcome Measure Data

Analysis Population Description
The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	156	165	110
Pre-specified infections	12 7.7%	18 10.9%	8 7.3%
Neoplasms: Benign, malignant, and unspecified	1 0.6%	2 1.2%	1 0.9%
Prespecified autoimmune symptoms and disorders	1 0.6%	1 0.6%	1 0.9%
Pre-specified infusional AEs	8 5.1%	30 18.2%	11 10%

15. Secondary Outcome

Title	DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, and AEs Leading to Discontinuation From Day 1 Through Day 365
Description	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame	From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study

Outcome Measure Data

Analysis Population Description
The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	156	165
Deaths	1 0.6%	2 1.2%
SAEs	15 9.6%	30 18.2%
Related SAEs	5 3.2%	14 8.5%
SAEs Leading to Discontinuation	4 2.6%	6 3.6%
AEs	139 89.1%	154 93.3%
Related AEs	72 46.2%	96 58.2%
AEs Leading to discontinuation	5 3.2%	12 7.3%

16. Secondary Outcome

Title	DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, and AEs Leading to Discontinuation From Day 198 Through Day 365 in Participants Receiving Placebo Switched to Abatacept
Description	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame	From Day 198 through Day 365, and up to 56 days after last dose if occurring on-study

Outcome Measure Data

Analysis Population Description
The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.

Arm/Group Title	PLA Switched to ABA + MTX [DB]
Arm/Group Description	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	110
Deaths	1 0.6%
SAEs	12 7.7%
Related SAEs	3 1.9%
SAEs Leading to Discontinuation	0 0%
AEs	71 45.5%
Related AEs	26 16.7%
AEs Leading to discontinuation	0 0%

17. Primary Outcome

Title	OL; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, and AEs Leading to Discontinuation
Description	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame	From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)

Outcome Measure Data

Analysis Population Description
All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.

Arm/Group Title	ABA + MTX [OL]
Arm/Group Description	All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	372
Deaths	3 1.9%
SAEs	90 57.7%
Related SAEs	12 7.7%
SAEs Leading to Discontinuation	5 3.2%
AEs	349 223.7%
Related AEs	165 105.8%
AEs Leading to discontinuation	10 6.4%

18. Primary Outcome

Title	OL; Number of Participants With AEs of Special Interest
Description	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
Time Frame	From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)

Outcome Measure Data

Analysis Population Description
All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.

Arm/Group Title	ABA + MTX [OL]
Arm/Group Description	All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	372
Infections	277 177.6%
Malignant neoplasms	3 1.9%
Benign and unspecified neoplasms	18 11.5%
Prespecified autoimmune symptoms and disorders	13 8.3%
Pre-specified peri-infusional AEs	50 32.1%
Pre-specified acute infusional AEs	28 17.9%

19. Primary Outcome

Title	OL; Number of Participants With Select Hematologic Laboratory Abnormalities
Description	High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Erythrocytes: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; lymphocytes: <0.750 x 10^3 c/uL/ >7.50 x 10^3 c/uL; monocytes: >2000 mm3; eosinophils: >0.750 x 10^3 c/uL;
Time Frame	From Day 366 through end of OL (range from 1.9 months to 42.3 months)

Outcome Measure Data

Analysis Population Description
All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.

Arm/Group Title	ABA + MTX [OL]
Arm/Group Description	All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	372
Low HGB (>3g/dL decrease from BL), n=372	9 5.8%
Low hematocrit (< 0.75 x BL), n=372	7 4.5%
Low erythrocytes (<0.75 x BL), n=372	6 3.8%
Low PLT (<0.67 x LLN), n=370	2 1.3%
High leukocytes (>1.25 x ULN), n=372	29 18.6%
Low neutrophils + bands (<1.0 x 10^3 c/uL), n=372	1 0.6%
Low lymphocytes (<0.75 x 10^3 c/uL), n=372	12 7.7%
High monocytes (>2000/mm^3), n=372	3 1.9%
High eosinophils (>0.750 x 10^3 c/uL), n=372	15 9.6%

20. Primary Outcome

Title	OL; Number of Participants With Select Blood Chemistry Laboratory Abnormalities
Description	Low=lower than LLN, High=greater than ULN. LLN/ULN= Alkaline phosphatase (ALP): >2 x ULN; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL
Time Frame	From Day 366 through end of OL (range from 1.9 months to 42.3 months)

Outcome Measure Data

Analysis Population Description
All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.

Arm/Group Title	ABA + MTX [OL]
Arm/Group Description	All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	371
High ALP (>2 x ULN)	1 0.6%
High AST (>3 x ULN)	4 2.6%
High ALT (>3 x ULN)	11 7.1%
High GGT (>2 x ULN)	16 10.3%
High total bilirubin (>2 x ULN)	1 0.6%
High BUN (>2 x BL)	17 10.9%
High creatinine (>1.5 increase from BL)	44 28.2%

21. Secondary Outcome

Title	DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 365
Description	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
Time Frame	From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study

Outcome Measure Data

Analysis Population Description
The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	156	165
Pre-specified infections	16 10.3%	30 18.2%
Neoplasms:Benign, malignant, and unspecified	1 0.6%	2 1.2%
Prespecified autoimmune symptoms and disorders	2 1.3%	1 0.6%
Pre-specified infusional AEs	11 7.1%	41 24.8%

22. Secondary Outcome

Title	DB; Number of Participants With AEs of Special Interest From Day 198 Through Day 365 in Participants Receiving Placebo Switched to Abatacept
Description	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
Time Frame	From Day 198 through Day 365, and up to 56 days after last dose if occurring on-study

Outcome Measure Data

Analysis Population Description
The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.

Arm/Group Title	PLA Switched to ABA + MTX [DB]
Arm/Group Description	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	110
Pre-specified infections	3 1.9%
Prespecified autoimmune symptoms and disorders	1 0.6%
Pre-specified infusional AEs	5 3.2%

23. Secondary Outcome

Title	DB; Number of Participants With Significant Changes in Mean Systolic and Diastolic Blood Pressure During Days 1 Through 197 and Days 1 Through 365
Description	Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
Time Frame	From Baseline (Day 1) through Day 197, or Day 1 through Day 365, and up to 56 days after last dose if occurring on-study

Outcome Measure Data

Analysis Population Description
As-Treated Population

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	156	165	110
Days 1-197	0 0%	0 0%	0 0%
Days 1-365	0 0%	0 0%	0 0%

24. Secondary Outcome

Title	DB; Number of Participants With Significant Changes in Mean Heart Rate During Days 1 Through 197 and Days 1 Through 365
Description	Heart Rate (HR) was assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
Time Frame	From Baseline (Day 1) through Day 197, or Day 1 through Day 365, and up to 56 days after last dose if occurring on-study

Outcome Measure Data

Analysis Population Description
As Treated Population.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	156	165	110
Days 1-197	0 0%	0 0%	0 0%
Days 1-365	0 0%	0 0%	0 0%

25. Secondary Outcome

Title	DB; Number of Participants With Significant Changes in Mean Temperature During Days 1 Through 197 and Days 1 Through 365
Description	Temperature (T) was assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
Time Frame	From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study

Outcome Measure Data

Analysis Population Description
As Treated Population.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	156	165	110
Days 1-197	0 0%	0 0%	0 0%
Days 1-365	0 0%	0 0%	0 0%

26. Secondary Outcome

Title	DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197
Description	High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; creatinine: >4 x BL
Time Frame	From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study

Outcome Measure Data

Analysis Population Description
The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	155	162	108
Low HGB (n=155, n=162, n=108)	1 0.6%	1 0.6%	1 0.9%
Low hematocrit (n=155, n=162, n=108)	0 0%	2 1.2%	0 0%
Low PLT (n=154, n=160, n=108)	1 0.6%	2 1.2%	0 0%
High PLT (n=154, n=160, n=108)	0 0%	0 0%	1 0.9%
Low leukocytes (n=155, n=162, n=108)	0 0%	1 0.6%	0 0%
High leukocytes (n=155, n=162, n=108)	6 3.8%	12 7.3%	16 14.5%
Low neutrophils + bands (n=155, n=162, n=108)	0 0%	0 0%	1 0.9%
High AST (n=155, n=162, n=108)	3 1.9%	3 1.8%	1 0.9%
High ALT (n=155, n=162, n=108)	3 1.9%	2 1.2%	3 2.7%
High creatinine (n=155, n=162, n=108)	6 3.8%	9 5.5%	5 4.5%

27. Secondary Outcome

Title	DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365
Description	High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; creatinine: >4 x BL
Time Frame	From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study

Outcome Measure Data

Analysis Population Description
The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA Switched to ABA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	156	164	109
Low HGB (n=156, n=164, n=109)	2 1.3%	1 0.6%	1 0.9%
Low hematocrit (n=156, n=164, n=109)	1 0.6%	2 1.2%	0 0%
Low PLT (n=155, n=162, n=109)	1 0.6%	2 1.2%	0 0%
High PLT (n=155, n=162, n=109)	0 0%	0 0%	1 0.9%
Low leukocytes (n=156, n=164, n=109)	0 0%	1 0.6%	0 0%
High leukocytes (n=156, n=164, n=109)	7 4.5%	22 13.3%	20 18.2%
Low neutrophils + bands (n=156, n=164, n=109)	0 0%	0 0%	1 0.9%
High AST (n=156, n=164, n=109)	4 2.6%	6 3.6%	3 2.7%
High ALT (n=156, n=164, n=109)	3 1.9%	7 4.2%	5 4.5%
High creatinine (n=156, n=164, n=109)	10 6.4%	13 7.9%	7 6.4%

28. Secondary Outcome

Title	DB; Number of Participants With Anti-Abatacept Antibodies From Day 1 Through Day 365 (Electrochemiluminescent [ECL] Immunoassay)
Description	ECL screened sera for drug-specific antibodies, immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction Category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing.
Time Frame	Day 1 through day 365

Outcome Measure Data

Analysis Population Description
The immunogenicity analysis population included participants who received at least one dose of abatacept and had immunogenicity samples collected at baseline and at least one post-baseline treatment visit.

Arm/Group Title	ABA + MTX [DB]	PLA Switched to ABA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	156	110
CTLA4 and Possibly Ig	0 0%	0 0%
Ig and/or Junction	0 0%	0 0%

29. Secondary Outcome

Title	DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Description	Infliximab levels were measured using a microplate enzyme-linked immunosorbant assay (ELISA) with infliximab bound to immobilized recombinant tumor necrosis factor (TNF)-alpha. Bound infliximab is detected utilizing a horseradish peroxidase-conjugated anti-human IgG Fc(fragment, crystallizable region)-specific). The enzyme turns over the substrate O-phenlenediamine to a chromogenic product that is measured at 490 nm. The cut-off value was 1.40 ug/mL; this was based on the mean (+ 3 SD) value in serum samples from 40 participants who had never received infliximab.
Time Frame	Day 1 through day 365

Outcome Measure Data

Analysis Population Description
The immunogenicity analysis population included participants who received at least one dose of infliximab and had immunogenicity samples collected at baseline and at least one post-baseline treatment visit.

Arm/Group Title	INF + MTX [DB]
Arm/Group Description	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	163
Overall anti-HACA	62.0 39.7%
Overall indeterminate anti-HACA	73.0 46.8%
Day 1 anti-HACA	0 0%
Day 1 indeterminate anti-HACA	3.7 2.4%
Day 113 anti-HACA	20.0 12.8%
Day 113 indeterminate anti-HACA	74.7 47.9%
Day 197 anti-HACA	42.2 27.1%
Day 197 indeterminate anti-HACA	33.3 21.3%
Day 309 anti-HACA	53.6 34.4%
Day 309 indeterminate anti-HACA	29.7 19%
Post Day 28 anti-HACA	52.2 33.5%
Post Day 28 indeterminate anti-HACA	27.5 17.6%
Discontinued, overall anti-HACA	60.9 39%
Discontinued, overall indeterminate anti-HACA	47.8 30.6%
Discontinued, post day 28 anti-HACA	55.0 35.3%
Discontinued, post day 28 indeterminate anti-HACA	25.0 16%
Discontinued, post day 56 anti-HACA	72.7 46.6%
Discontinued, post day 56 indeterminate anti-HACA	9.1 5.8%
Discontinued, post day 85 anti-HACA	88.9 57%
Discontinued, post day 85 indeterminate anti-HACA	0 0%
Missed doses, overall anti-HACA	73.1 46.9%
Missed doses, overall indeterminate anti-HACA	76.9 49.3%
Missed 1 dose, anti-HACA	72.0 46.2%
Missed 1 dose, indeterminate anti-HACA	76.0 48.7%
Missed >1 dose, anti-HACA	100.0 64.1%
Missed >1 dose, indeterminate anti-HACA	100.0 64.1%

30. Primary Outcome

Title	OL; Mean Change From Baseline to Day 365 in Hemoglobin, Total Protein, and Albumin
Description	Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN
Time Frame	Baseline (Day 1), Day 365

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	131	136	104
HGB (n=131, n=135, n=103)	0.53 (0.09)	0.24 (0.09)	0.43 (0.09)
Total protein (n=131, n=136, n=104)	-0.09 (0.04)	0.11 (0.04)	-0.12 (0.04)
Albumin (n=131, n=136, n=104)	0.12 (0.03)	0.00 (0.03)	0.05 (0.03)

31. Primary Outcome

Title	OL; Mean Change From Baseline to Day 365 in Platelets
Description	Platelets (PLT): <0.67 x LLN, >1.5 x ULN
Time Frame	Baseline (Day 1), Day 365

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	129	129	102
Mean (Standard Error) [10^9 c/L]	-42.4 (5.20)	-35.5 (6.93)	-28.4 (6.75)

32. Primary Outcome

Title	OL; Mean Change From Baseline to Day 365 in Hematocrit
Description	Hematocrit: <0.75 x BL
Time Frame	Baseline (Day 1), Day 365

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	129	134	102
Mean (Standard Error) [percentage red blood cells]	1.44 (0.29)	0.51 (0.27)	1.03 (0.27)

33. Primary Outcome

Title	OL; Mean Change From Baseline to Day 365 in White Blood Cells
Description	Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.
Time Frame	Baseline (Day 1), Day 365

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	131	134	104
Leukocytes (n=131, n=134, n=103)	-0.95 (0.23)	-0.90 (0.21)	-0.84 (0.23)
Neutrophils + bands (n=130, n=130, n=104)	-0.91 (0.20)	-1.14 (0.20)	-1.05 (0.22)
Basophils (n=130, n=130, n=101)	-0.01 (0.00)	0.00 (0.00)	0.00 (0.00)
Monocytes (n=130, n=130, n=101)	-0.01 (0.02)	-0.01 (0.02)	0.02 (0.02)
Eosinophils (n=130, n=130, n=101)	-0.04 (0.01)	-0.02 (0.02)	-0.03 (0.01)
Lymphocytes (n=130, n=130, n=101)	0.03 (0.07)	0.24 (0.06)	0.22 (0.08)

34. Primary Outcome

Title	OL; Mean Change From Baseline to Day 365 in Erythrocytes
Description	Erythrocytes: <0.75 x BL
Time Frame	Baseline (Day 1), Day 365

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	131	135	103
Mean (Standard Error) [10^6 c/uL]	0.09 (0.03)	0.00 (0.03)	0.006 (0.03)

35. Primary Outcome

Title	OL; Mean Change From Baseline to Day 365 in Electrolytes
Description	Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN
Time Frame	Baseline (Day 1), Day 365

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	131	136	104
Na (n=131, n=136, n=104)	-1.62 (0.29)	-1.57 (0.33)	-1.09 (0.38)
K (n=131, n=135, n=104)	-0.03 (0.04)	-0.07 (0.04)	-0.03 (0.05)
Cl (n=131, n=136, n=104)	-1.40 (0.28)	-1.18 (0.31)	-1.06 (0.33)

36. Primary Outcome

Title	OL; Mean Change From Baseline to Day 365 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Description	Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;
Time Frame	Baseline (Day 1), Day 365

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	131	136	104
Creatinine (n=131, n=136, n=104)	0.03 (0.02)	0.02 (0.01)	0.01 (0.02)
BUN (n=131, n=136, n=104)	-0.31 (0.41)	-0.52 (0.40)	0.10 (0.53)
Ca (n=131, n=136, n=104)	0.14 (0.04)	0.08 (0.03)	0.14 (0.04)
P (n=131, n=136, n=104)	0.03 (0.05)	-0.01 (0.05)	0.05 (0.05)
Uric Acid (n=131, n=136, n=104)	0.09 (0.08)	0.08 (0.10)	0.04 (0.12)
Total bilirubin (n=131, n=134, n=104)	0.06 (0.01)	0.04 (0.02)	0.03 (0.02)
Serum glucose (n=131, n=136, n=104)	5.66 (2.41)	2.49 (3.15)	3.03 (2.16)

37. Primary Outcome

Title	OL; Mean Change From Baseline to Day 365 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
Description	alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN
Time Frame	Baseline (Day 1), Day 365

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	131	136	104
ALT (n=131, n=135, n=104)	3.51 (1.33)	2.19 (2.31)	-0.04 (1.68)
AST (n=131, n=135, n=104)	0.54 (1.04)	-0.11 (1.51)	-2.23 (1.41)
GGT (n=131, n=135, n=104)	2.53 (2.81)	-0.61 (1.76)	-2.32 (2.73)
ALP (n=131, n=136, n=104)	-0.53 (2.16)	-7.78 (2.24)	-4.34 (2.48)

38. Primary Outcome

Title	OL; Mean Change From Baseline to Day 729 in Hemoglobin, Total Protein, and Albumin
Description	Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN
Time Frame	Baseline (Day 1), Day 729

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	124	127	102
HGB (n=124, n=125, n=102)	0.66 (0.10)	0.48 (0.10)	0.40 (0.13)
Total protein (n=124, n=127, n=102)	-0.33 (0.05)	-0.25 (0.04)	-0.29 (0.05)
Albumin (n=124, n=127, n=102)	0.13 (0.03)	0.10 (0.03)	0.06 (0.03)

39. Primary Outcome

Title	OL; Mean Change From Baseline to Day 729 in Platelets
Description	Platelets (PLT): <0.67 x LLN, >1.5 x ULN
Time Frame	Baseline (Day 1), Day 729

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	124	122	100
Mean (Standard Error) [10^9 c/L]	-63.9 (6.04)	-5832 (7.66)	-47.7 (8.16)

40. Primary Outcome

Title	OL; Mean Change From Baseline to Day 729 in Hematocrit
Description	Hematocrit: <0.75 x BL
Time Frame	Baseline (Day 1), Day 729

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	124	124	102
Mean (Standard Error) [percentage of red blood cells]	1.72 (0.29)	1.23 (0.29)	0.99 (0.38)

41. Secondary Outcome

Title	OL; Mean Change From Baseline Over Time in DAS 28 (ESR) Score
Description	The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.
Time Frame	Baseline (Day 1), Day 365, Day 533, Day 729

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period.n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants <60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants >100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	132	136	104
Day 365 (n=122, n=130, n=94)	-3.12 (0.13)	-2.39 (0.13)	-2.81 (0.16)
Day 533 (n=118, n=121, n=92)	-3.21 (0.13)	-3.04 (0.13)	-2.84 (0.17)
Day 729 (n=110, n=121, n=93)	-3.35 (0.14)	-3.29 (0.12)	-2.98 (0.17)

42. Secondary Outcome

Title	OL; Percentage of Participants With DAS28 (ESR) Remission and Low Disease Activity (LDAS) Over Time
Description	The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.
Time Frame	Baseline (Day 1), Day 365, Day 533, Day 729

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Efficacy data was summarized for the 3 DB treatment cohorts.n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants <60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants >100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	132	136	104
Day 365 Remission (n=127, n=135, n=102)	19.7 12.6%	13.3 8.1%	15.7 14.3%
Day 365 LDAS (n=127, n=135, n=102)	37.0 23.7%	23.0 13.9%	29.4 26.7%
Day 533 Remission (n=122, n=125, n=98)	20.5 13.1%	20.0 12.1%	19.4 17.6%
Day 533 LDAS (n=122, n=125, n=98)	37.7 24.2%	33.6 20.4%	35.7 32.5%
Day 729 Remission (n=115, n=126, n=100)	26.1 16.7%	28.6 17.3%	22.0 20%
Day 729 LDAS (n=115, n=126, n=100)	41.7 26.7%	45.2 27.4%	34.0 30.9%

43. Secondary Outcome

Title	OL; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Over Time
Description	The DAS28 is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= > 5.1, low disease activity= < 3.2, and remission= < 2.6. Clinically significant response= decrease of >1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute <3.2 or >1.2 improvement from baseline [BL]), moderate (absolute 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute >5.1 or <0.6 change from BL)
Time Frame	DB Days 365, 533, and 729

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period.n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	132	136	104
Day 365 Good response (n=122, n=130, n=94)	38.5 24.7%	23.1 14%	30.9 28.1%
Day 365 Moderate response (n=122, n=130, n=94)	53.3 34.2%	58.5 35.5%	55.3 50.3%
Day 365 No response (n=122, n=130, n=94)	8.2 5.3%	18.5 11.2%	13.8 12.5%
Day 533 Good response (n=118, n=121, n=92)	38.1 24.4%	33.1 20.1%	35.9 32.6%
Day 533 Moderate response (n=118, n=121, n=92)	58.5 37.5%	58.7 35.6%	53.3 48.5%
Day 533 No response (n=118, n=121, n=92)	3.4 2.2%	8.3 5%	10.9 9.9%
Day 729 Good response (n=110, n=121, n=93)	41.8 26.8%	45.5 27.6%	34.4 31.3%
Day 729 Moderate response (n=110, n=121, n=93)	53.6 34.4%	47.9 29%	51.6 46.9%
Day 729 No response (n=110, n=121, n=93)	4.5 2.9%	6.6 4%	14.0 12.7%

44. Secondary Outcome

Title	OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time
Description	The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein [CRP]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.
Time Frame	DB Day 197, Day 365, Day 533, Day 729

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	132	136	104
Day 197, ACR 20 (n=130, n=133, n=102)	73.1 46.9%	68.4 41.5%	44.1 40.1%
Day 197, ACR 50 (n=129, n=134, n=103)	45.7 29.3%	42.5 25.8%	21.4 19.5%
Day 197, ACR 70 (n=130, n=133, n=103)	23.1 14.8%	27.1 16.4%	10.7 9.7%
Day 365, ACR 20 (n=130, n=136, n=103)	88.5 56.7%	69.1 41.9%	75.7 68.8%
Day 365, ACR 50 (n=131, n=136, n=102)	55.0 35.3%	43.4 26.3%	54.9 49.9%
Day 365, ACR 70 (n=131, n=136, n=102)	31.3 20.1%	23.5 14.2%	31.4 28.5%
Day 533, ACR 20 (n=128, n=128, n=102)	82.8 53.1%	82.8 50.2%	74.5 67.7%
Day 533, ACR 50 (n=129, n=128, n=103)	58.1 37.2%	57.0 34.5%	47.6 43.3%
Day 533, ACR 70 (n=129, n=127, n=102)	35.7 22.9%	40.9 24.8%	32.4 29.5%
Day 729, ACR 20 (n=119, n=127, n=102)	86.6 55.5%	84.3 51.1%	76.5 69.5%
Day 729, ACR 50 (n=117, n=127, n=101)	60.7 38.9%	70.9 43%	49.5 45%
Day 729, ACR 70 (n=120, n=127, n=100)	40.8 26.2%	44.9 27.2%	33.0 30%

45. Secondary Outcome

Title	OL; Percentage of Participants Who Achieved Major Clinical Response
Description	Major Clinical Response was defined as a continuous ACR 70 for six months.
Time Frame	Defined from the date of achieving ACR 70 response to 6 months post response

Outcome Measure Data

Analysis Population Description
Protocol-specified analyses of the proportion of participants achieving a Major Clinical Response were not performed since ACR responses in the open-label period could only be assessed at 6-month intervals due to the fact that CRP and ESR were only measured every 6 months during this period.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants <60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants >100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	0	0	0

46. Secondary Outcome

Title	OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time
Description	The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
Time Frame	OL Days 197, 253, 281, 309, 337, 365, 449, 533, 617, and 729

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period.n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	132	136	104
Day 197 (n=131, n=134, n=103)	70.2 45%	68.7 41.6%	42.7 38.8%
Day 225 (n=132, n=133, n=101)	75.0 48.1%	72.9 44.2%	52.5 47.7%
Day 253 (n=130, n=135, n=102)	71.5 45.8%	65.2 39.5%	57.8 52.5%
Day 281 (n=131, n=135, n=102)	73.3 47%	71.9 43.6%	52.0 47.3%
Day 309 (n=131, n=134, n=102)	71.0 45.5%	70.1 42.5%	62.7 57%
Day 337 (n=130, n=136, n=101)	71.5 45.8%	72.1 43.7%	63.4 57.6%
Day 365 (n=130, n=136, n=103)	70.8 45.4%	67.6 41%	61.2 55.6%
Day 449 (n=129, n=133, n=101)	70.5 45.2%	72.9 44.2%	64.4 58.5%
Day 533 (n=128, n=127, n=103)	74.2 47.6%	78.0 47.3%	61.2 55.6%
Day 617 (n=123, n=127, n=103)	78.9 50.6%	79.5 48.2%	64.1 58.3%
Day 729 (n=122, n=127, n=103)	74.6 47.8%	78.0 47.3%	63.1 57.4%

47. Secondary Outcome

Title	OL; Adjusted Mean Change From Baseline to Day 729 in HAQ-DI
Description	The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
Time Frame	Day 1 (Baseline), Day 729

Outcome Measure Data

Analysis Population Description
All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	122	127	103
HAQ-DI	-0.83 (0.06)	-0.84 (0.06)	-0.64 (0.07)
HAQ-DI component: dressing and grooming	-0.93 (0.08)	-91.0 (0.08)	-0.68 (0.09)
HAQ-DI component: arising	-0.8 (0.09)	-0.77 (0.08)	-0.72 (0.09)
HAQ-DI component: eating	-0.86 (0.09)	-0.99 (0.09)	-0.82 (0.10)
HAQ-DI component: walking	-0.78 (0.09)	-0.73 (0.08)	-0.54 (0.08)
HAQ-DI component: hygiene	-0.65 (0.10)	-0.65 (0.08)	-0.5 (0.09)
HAQ-DI component: reach	-0.97 (0.09)	-0.94 (0.10)	-0.64 (0.09)
HAQ-DI component: grip	-0.88 (0.09)	-0.96 (0.09)	-0.61 (0.09)
HAQ-DI component: activities	-0.75 (0.09)	-0.73 (0.09)	-0.61 (0.09)

48. Primary Outcome

Title	OL; Mean Change From Baseline to Day 729 in White Blood Cells
Description	Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.
Time Frame	Baseline (Day 1), Day 729

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	124	125	102
Leukocytes (n=124, n=125, n=102)	-1.57 (0.23)	-1.23 (0.26)	-1.28 (0.23)
Neutrophils + bands (n=123, n=123, n=101)	-1.62 (0.21)	-1.35 (0.23)	-1.33 (0.22)
Basophils (n=123, n=123, n=101)	-0.01 (0.00)	0.00 (0.00)	-0.01 (0.00)
Monocytes (n=123, n=123, n=101)	-0.05 (0.02)	-0.02 (0.04)	-0.03 (0.02)
Eosinophils (n=123, n=123, n=101)	-0.01 (0.01)	-0.03 (0.02)	-0.05 (0.02)
Lymphocytes (n=123, n=123, n=101)	0.13 (0.06)	0.18 (0.06)	0.08 (0.06)

49. Primary Outcome

Title	OL; Mean Change From Baseline to Day 729 in Erythrocytes
Description	Erythrocytes: <0.75 x BL
Time Frame	Baseline (Day 1), Day 729

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	124	125	102
Mean (Standard Error) [10^6 c/uL]	0.07 (0.03)	0.04 (0.03)	0.02 (0.04)

50. Primary Outcome

Title	OL; Mean Change From Baseline to Day 729 in Electrolytes
Description	Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN
Time Frame	Baseline (Day 1), Day 729

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	124	127	102
Na	-1.10 (0.28)	-1.12 (0.29)	-1.22 (0.38)
K	-0.03 (0.04)	-0.04 (0.04)	-0.02 (0.04)
Cl	-1.31 (0.26)	-1.28 (0.31)	-2.03 (0.29)

51. Primary Outcome

Title	OL; Mean Change From Baseline to Day 729 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Description	Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;
Time Frame	Baseline (Day 1), Day 729

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	124	127	102
Creatinine (n=124, n=127, n=102)	0.08 (0.02)	0.08 (0.01)	0.07 (0.02)
BUN (n=124, n=127, n=102)	-0.37 (0.43)	-0.12 (0.44)	0.20 (0.46)
Ca (n=124, n=127, n=102)	0.01 (0.04)	-0.01 (0.05)	0.02 (0.05)
P (n=124, n=127, n=102)	-0.05 (0.05)	-0.16 (0.06)	-0.08 (0.06)
Uric Acid (n=124, n=127, n=102)	-0.22 (0.08)	-0.02 (0.09)	-0.10 (0.12)
Total bilirubin (n=124, n=127, n=101)	0.01 (0.02)	0.04 (0.02)	0.03 (0.02)
Serum glucose (n=123, n=126, n=101)	9.92 (3.04)	7.52 (2.02)	3.74 (2.17)

52. Primary Outcome

Title	OL; Mean Change From Baseline to Day 729 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
Description	alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN
Time Frame	Baseline (Day 1), Day 729

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	124	127	102
ALT	2.73 (1.59)	1.02 (1.83)	-0.89 (1.96)
AST	0.03 (1.17)	-0.22 (1.22)	-2.45 (1.60)
GGT	1.23 (2.38)	-0.41 (2.14)	-1.93 (2.95)
ALP	-0.55 (2.17)	-2.61 (2.83)	-3.91 (3.41)

53. Primary Outcome

Title	OL; Mean Change From Baseline to Day 1121 in Hemoglobin, Total Protein, and Albumin
Description	Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN
Time Frame	Baseline (Day 1), Day 1121

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	102	98	86
HGB (n=102, n=98, n=85)	0.66 (0.13)	0.53 (0.14)	0.57 (0.13)
Total protein (n=102, n=98, n=86)	-0.35 (0.05)	-0.24 (0.05)	-0.33 (0.05)
Albumin (n=102, n=98, n=86)	0.04 (0.04)	0.08 (0.04)	-0.01 (0.04)

54. Primary Outcome

Title	OL; Mean Change From Baseline to Day 1121 in Platelets
Description	Platelets (PLT): <0.67 x LLN, >1.5 x ULN
Time Frame	Baseline (Day 1), Day 1121

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	101	95	85
Mean (Standard Error) [10^9 c/L]	-67.5 (7.49)	-66.1 (8.86)	-62.5 (8.05)

55. Primary Outcome

Title	OL; Mean Change From Baseline to Day 1121 in Hematocrit
Description	Hematocrit: <0.75 x BL
Time Frame	Baseline (Day 1), Day 1121

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	100	98	85
Mean (Standard Error) [percentage of red blood cells]	1.83 (0.37)	1.50 (0.39)	1.47 (0.39)

56. Primary Outcome

Title	OL; Mean Change From Baseline to Day 1121 in White Blood Cells
Description	Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.
Time Frame	Baseline (Day 1), Day 1121

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	102	98	85
Leukocytes (n=102, n=98, n=85)	-1.07 (0.27)	-1.09 (0.26)	-0.99 (0.25)
Neutrophils + bands (n=99, n=96, n=84)	-1.17 (0.25)	-1.40 (0.25)	-1.28 (0.24)
Basophils (n=99, n=96, n=85)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
Monocytes (n=99, n=96, n=84)	0.03 (0.02)	0.00 (0.03)	0.01 (0.03)
Eosinophils (n=99, n=96, n=84)	0.00 (0.01)	-0.06 (0.02)	-0.04 (0.02)
Lymphocytes (n=99, n=96, n=84)	0.16 (0.08)	0.34 (0.07)	0.32 (0.10)

57. Primary Outcome

Title	OL; Mean Change From Baseline to Day 1121 in Erythrocytes
Description	Erythrocytes: <0.75 x BL
Time Frame	Baseline (Day 1), Day 1121

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	102	98	85
Mean (Standard Error) [10^6 c/uL]	0.11 (0.03)	0.11 (0.04)	0.12 (0.04)

58. Primary Outcome

Title	OL; Mean Change From Baseline to Day 1121 in Electrolytes
Description	Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN
Time Frame	Baseline (Day 1), Day 1121

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	102	98	86
Na (n=102, n=98, n=86)	-1.80 (0.33)	-1.38 (0.38)	-1.34 (0.42)
K (n=102, n=98, n=85)	0.01 (0.04)	0.08 (0.05)	0.01 (0.05)
Cl (n=102, n=98, n=86)	-0.88 (0.35)	-0.94 (0.38)	-1.42 (0.37)

59. Primary Outcome

Title	OL; Mean Change From Baseline to Day 1121 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Description	Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;
Time Frame	Baseline (Day 1), Day 1121

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	102	98	86
Creatinine (n=102, n=98, n=86)	0.06 (0.02)	0.07 (0.03)	0.08 (0.02)
BUN (n=102, n=98, n=86)	-0.04 (0.49)	0.34 (0.73)	0.20 (0.56)
Ca (n=102, n=98, n=86)	-0.01 (0.05)	-0.03 (0.06)	0.04 (0.05)
P (n=102, n=98, n=85)	-0.18 (0.07)	-0.19 (0.07)	-0.11 (0.06)
Uric Acid (n=102, n=98, n=86)	-0.05 (0.11)	0.13 (0.10)	0.20 (0.15)
Total bilirubin (n=102, n=98, n=86)	0.02 (0.02)	0.03 (0.02)	0.03 (0.02)
Serum glucose (n=101, n=98, n=85)	12.99 (3.31)	6.91 (2.10)	9.07 (3.20)

60. Primary Outcome

Title	OL; Mean Change From Baseline to Day 1121 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
Description	alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN
Time Frame	Baseline (Day 1), Day 1121

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	102	98	86
ALT (n=102, n=98, n=86)	4.74 (1.95)	4.66 (2.88)	-0.35 (2.33)
AST (n=102, n=98, n=86)	3.79 (1.60)	4.49 (2.13)	0.38 (1.69)
GGT (n=102, n=98, n=86)	1.60 (2.79)	-2.88 (2.16)	-0.14 (3.79)
ALP (n=88, n=79, n=69)	1.25 (2.62)	-4.03 (3.79)	-7.35 (3.53)

61. Primary Outcome

Title	OL; Mean Change From Baseline to Day 1513 in Hemoglobin, Total Protein, and Albumin
Description	Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN
Time Frame	Baseline (Day 1), Day 1513

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	23	20	16
HGB	0.25 (0.33)	0.44 (0.31)	0.56 (0.32)
Total protein	-0.73 (0.09)	-0.33 (0.11)	-0.34 (0.14)
Albumin	-0.06 (0.07)	0.10 (0.07)	0.00 (0.11)

62. Primary Outcome

Title	OL; Mean Change From Baseline to Day 1513 in Platelets
Description	Platelets (PLT): <0.67 x LLN, >1.5 x ULN
Time Frame	Baseline (Day 1), Day 1513

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	23	19	16
Mean (Standard Error) [10^9 c/L]	-78.0 (17.20)	-74.0 (16.18)	-99.2 (19.83)

63. Primary Outcome

Title	OL; Mean Change From Baseline to Day 1513 in Hematocrit
Description	Hematocrit: <0.75 x BL
Time Frame	Baseline (Day 1), Day 1513

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	23	19	16
Mean (Standard Error) [percentage of red blood cells]	0.92 (1.00)	1.28 (0.92)	1.18 (1.00)

64. Primary Outcome

Title	OL; Mean Change From Baseline to Day 1513 in White Blood Cells
Description	Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.
Time Frame	Baseline (Day 1), Day 1513

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	23	20	16
Leukocytes (n=23, n=20, n=16)	-0.34 (0.45)	-1.08 (0.63)	-2.13 (0.50)
Neutrophils + bands (n=22, n=17, n=16)	-0.37 (0.33)	-1.03 (0.68)	-1.93 (0.50)
Basophils (n=22, n=17, n=16)	0.00 (0.01)	-0.01 (0.01)	-0.01 (0.01)
Monocytes (n=22, n=17, n=16)	0.01 (0.03)	-0.10 (0.09)	-0.05 (0.04)
Eosinophils (n=22, n=17, n=16)	0.04 (0.06)	-0.11 (0.16)	-0.23 (0.00)
Lymphocytes (n=22, n=17, n=16)	0.20 (0.14)	0.16 (0.16)	-0.15 (0.16)

65. Primary Outcome

Title	OL; Mean Change From Baseline to Day 1513 in Erythrocytes
Description	Erythrocytes: <0.75 x BL
Time Frame	Baseline (Day 1), Day 1513

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	23	19	16
Mean (Standard Error) [10^6 c/uL]	-0.10 (0.09)	0.00 (0.09)	-0.09 (0.08)

66. Primary Outcome

Title	OL; Mean Change From Baseline to Day 1513 in Electrolytes
Description	Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN
Time Frame	Baseline (Day 1), Day 1513

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	23	20	16
Na (n=22, n=20, n=16)	-4.36 (0.73)	-3.80 (0.99)	-4.50 (0.74)
K (n=23, n=20, n=16)	-0.16 (0.10)	-0.32 (0.08)	-0.46 (0.11)
Cl (n=23, n=20, n=16)	-2.48 (0.71)	-2.60 (0.84)	-4.13 (0.88)

67. Primary Outcome

Title	OL; Mean Change From Baseline to Day 1513 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Description	Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;
Time Frame	Baseline (Day 1), Day 1513

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	23	20	16
Creatinine	0.10 (0.02)	0.05 (0.04)	0.08 (0.06)
BUN	2.87 (0.90)	-0.40 (1.13)	0.63 (1.36)
Ca	0.27 (0.07)	0.38 (0.09)	0.35 (0.12)
P	-0.09 (0.11)	-0.51 (0.16)	-0.17 (0.13)
Uric Acid	0.03 (0.18)	0.06 (0.21)	0.33 (0.33)
Total bilirubin	0.08 (0.10)	0.09 (0.03)	0.23 (0.14)
Serum glucose	8.87 (3.19)	9.00 (1.88)	8.44 (4.38)

68. Primary Outcome

Title	OL; Mean Change From Baseline to Day 1513 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
Description	alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN
Time Frame	Baseline (Day 1), Day 1513

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.

Arm/Group Title	ABA + MTX [DB]	INF + MTX [DB]	PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).	Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)	Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
Measure Participants	23	20	16
ALT	-1.87 (2.73)	-9.20 (3.75)	2.44 (8.07)
AST	-1.35 (1.72)	-2.85 (2.55)	0.38 (7.23)
GGT	-3.00 (2.99)	-10.9 (5.79)	-3.06 (10.30)
ALP	-15.8 (5.23)	-18.7 (7.12)	-11.30 (7.80)

69. Primary Outcome

Title	OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Description	Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP), units=mm mercury (Hg)
Time Frame	Days 365, 729, 1121, and 1513

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.n=number of participants with data available.

Arm/Group Title	ABA + MTX [OL]
Arm/Group Description	All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	372
Day 365 SBP pre-dose (n=343)	119.0 (15.03)
Day 365 SBP post-dose (n=341)	118.8 (15.35)
Day 729 SBP pre-dose (n=321)	120.4 (15.20)
Day 729 SBP post-dose (n=323)	119.5 (15.02)
Day 1121 SBP pre-dose (n=265)	121.1 (15.59)
Day 1121 SBP post-dose (n=265)	119.2 (13.99)
Day 1513 SBP pre-dose (n=52)	114.6 (13.57)
Day 1513 SBP post-dose (n=52)	114.2 (12.90)
Day 365 DBP pre-dose (n=343)	74.5 (9.80)
Day 365 DBP post-dose (n=341)	74.0 (10.18)
Day 729 DBP pre-dose (n=321)	74.9 (9.69)
Day 729 DBP post-dose (n=323)	74.6 (9.92)
Day 1121 DBP pre-dose (n=265)	74.9 (9.45)
Day 1121 DBP post-dose (n=265)	73.6 (9.12)
Day 1513 DBP pre-dose (n=52)	71.7 (9.45)
Day 1513 DBP post-dose (n=52)	72.1 (9.11)

70. Primary Outcome

Title	OL; Mean Heart Rate (HR) During Open Label Period
Description	Heart Rate (HR), units=beats per minute (bpm)
Time Frame	Days 365, 729, 1121, and 1513

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.n=number of participants with data available.

Arm/Group Title	ABA + MTX [OL]
Arm/Group Description	All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	372
Day 365 HR pre-dose (n=343)	74.2 (9.30)
Day 365 HR post-dose (n=341)	74.1 (8.57)
Day 729 HR pre-dose (n=322)	74.2 (9.12)
Day 729 HR post-dose (n=324)	73.4 (8.59)
Day 1121 HR pre-dose (n=265)	73.9 (9.31)
Day 1121 HR post-dose (n=265)	73.8 (9.46)
Day 1513 HR pre-dose (n=52)	73.0 (8.38)
Day 1513 HR post-dose (n=52)	73.8 (7.16)

71. Primary Outcome

Title	OL; Mean Temperature (T) During Open Label Period
Description	Temperature (T), units=degrees Celcius
Time Frame	Days 365, 729, 1121, and 1513

Outcome Measure Data

Analysis Population Description
Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.n=number of participants with data available.

Arm/Group Title	ABA + MTX [OL]
Arm/Group Description	All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
Measure Participants	372
Day 365 T pre-dose (n=339)	36.3 (0.43)
Day 365 T post-dose (n=339)	36.3 (0.41)
Day 729 T pre-dose (n=320)	36.3 (0.45)
Day 729 T post-dose (n=323)	36.3 (0.42)
Day 1121 T pre-dose (n=263)	36.2 (0.51)
Day 1121 T post-dose (n=264)	36.2 (0.47)
Day 1513 T pre-dose (n=52)	36.1 (0.35)
Day 1513 T post-dose (n=52)	36.1 (0.37)

Adverse Events

	ABA (DB)		ABA + MTX [OL]		INF + MTX [DB]		PLA + MTX [DB]
Time Frame
Adverse Event Reporting Description

Arm/Group Title	ABA (DB)		ABA + MTX [OL]		INF + MTX [DB]		PLA + MTX [DB]
Arm/Group Description	Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants > 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).		All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).		Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly).		Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, 104 participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	ABA (DB)		ABA + MTX [OL]		INF + MTX [DB]		PLA + MTX [DB]
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/156 (10.9%)		90/372 (24.2%)		30/165 (18.2%)		21/110 (19.1%)
Blood and lymphatic system disorders
ANAEMIA	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
THROMBOCYTOPENIA	1/156 (0.6%)		0/372 (0%)		0/165 (0%)		0/110 (0%)
Cardiac disorders
ARRHYTHMIA	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
PERICARDITIS	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
ANGINA PECTORIS	1/156 (0.6%)		1/372 (0.3%)		1/165 (0.6%)		0/110 (0%)
ANGINA UNSTABLE	1/156 (0.6%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
CARDIAC FAILURE	0/156 (0%)		1/372 (0.3%)		1/165 (0.6%)		0/110 (0%)
ATRIAL TACHYCARDIA	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
MYOCARDIAL INFARCTION	0/156 (0%)		3/372 (0.8%)		0/165 (0%)		0/110 (0%)
CORONARY ARTERY DISEASE	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
CORONARY ARTERY OCCLUSION	1/156 (0.6%)		0/372 (0%)		0/165 (0%)		0/110 (0%)
ACUTE MYOCARDIAL INFARCTION	0/156 (0%)		2/372 (0.5%)		0/165 (0%)		0/110 (0%)
Ear and labyrinth disorders
VERTIGO	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
Endocrine disorders
ADRENAL INSUFFICIENCY	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
Eye disorders
CATARACT	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
CORNEAL PERFORATION	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
Gastrointestinal disorders
DIARRHOEA	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
GASTRITIS	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
ANAL FISSURE	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
ABDOMINAL PAIN	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
ANAL SKIN TAGS	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
INGUINAL HERNIA	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
UMBILICAL HERNIA	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
PANCREATITIS ACUTE	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
HYPERTROPHIC ANAL PAPILLA	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
UPPER GASTROINTESTINAL HAEMORRHAGE	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
General disorders
PYREXIA	1/156 (0.6%)		2/372 (0.5%)		0/165 (0%)		0/110 (0%)
HYPERTHERMIA	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
Hepatobiliary disorders
BILIARY COLIC	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
CHOLELITHIASIS	1/156 (0.6%)		2/372 (0.5%)		1/165 (0.6%)		0/110 (0%)
Immune system disorders
ANAPHYLACTIC SHOCK	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
Infections and infestations
SEPSIS	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
ABSCESS	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
PNEUMONIA	2/156 (1.3%)		1/372 (0.3%)		3/165 (1.8%)		1/110 (0.9%)
SINUSITIS	1/156 (0.6%)		0/372 (0%)		0/165 (0%)		0/110 (0%)
BRONCHITIS	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
CELLULITIS	0/156 (0%)		3/372 (0.8%)		1/165 (0.6%)		0/110 (0%)
ERYSIPELAS	0/156 (0%)		1/372 (0.3%)		1/165 (0.6%)		0/110 (0%)
APPENDICITIS	0/156 (0%)		2/372 (0.5%)		0/165 (0%)		0/110 (0%)
SEPTIC SHOCK	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
HERPES ZOSTER	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
OSTEOMYELITIS	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
GASTROENTERITIS	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
LOBAR PNEUMONIA	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
WOUND INFECTION	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
BURSITIS INFECTIVE	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
ABSCESS SOFT TISSUE	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
ENCEPHALITIS HERPES	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
INFECTED SKIN ULCER	1/156 (0.6%)		0/372 (0%)		0/165 (0%)		0/110 (0%)
SUBCUTANEOUS ABSCESS	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
NECROTISING FASCIITIS	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
PULMONARY TUBERCULOSIS	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
APPENDICITIS PERFORATED	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
PERITONEAL TUBERCULOSIS	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
URINARY TRACT INFECTION	0/156 (0%)		5/372 (1.3%)		0/165 (0%)		0/110 (0%)
LUNG INFECTION PSEUDOMONAL	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
POSTOPERATIVE WOUND INFECTION	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		1/110 (0.9%)
PNEUMOCYSTIS JIROVECI PNEUMONIA	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
Injury, poisoning and procedural complications
FALL	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
ACCIDENT	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
HIP FRACTURE	1/156 (0.6%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
ANKLE FRACTURE	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
ILIUM FRACTURE	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
TENDON RUPTURE	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
TIBIA FRACTURE	1/156 (0.6%)		0/372 (0%)		0/165 (0%)		0/110 (0%)
CARTILAGE INJURY	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
MULTIPLE INJURIES	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
FAILURE OF IMPLANT	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
SUBDURAL HAEMATOMA	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
ACCIDENTAL OVERDOSE	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
LOWER LIMB FRACTURE	0/156 (0%)		1/372 (0.3%)		1/165 (0.6%)		0/110 (0%)
PUBIC RAMI FRACTURE	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
UPPER LIMB FRACTURE	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
COMPLICATED FRACTURE	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
ROAD TRAFFIC ACCIDENT	1/156 (0.6%)		0/372 (0%)		0/165 (0%)		0/110 (0%)
LUMBAR VERTEBRAL FRACTURE	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
POST PROCEDURAL HAEMATOMA	1/156 (0.6%)		0/372 (0%)		0/165 (0%)		0/110 (0%)
CERVICAL VERTEBRAL FRACTURE	1/156 (0.6%)		0/372 (0%)		0/165 (0%)		0/110 (0%)
POST PROCEDURAL COMPLICATION	0/156 (0%)		2/372 (0.5%)		0/165 (0%)		0/110 (0%)
DISLOCATION OF JOINT PROSTHESIS	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
Investigations
HORMONE LEVEL ABNORMAL	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
ALANINE AMINOTRANSFERASE INCREASED	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
ASPARTATE AMINOTRANSFERASE INCREASED	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
Metabolism and nutrition disorders
DEHYDRATION	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		1/110 (0.9%)
HYPOGLYCAEMIA	1/156 (0.6%)		0/372 (0%)		0/165 (0%)		0/110 (0%)
DIABETES MELLITUS	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
Musculoskeletal and connective tissue disorders
FISTULA	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
ARTHRITIS	0/156 (0%)		4/372 (1.1%)		0/165 (0%)		0/110 (0%)
ARTHRALGIA	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
OSTEONECROSIS	1/156 (0.6%)		2/372 (0.5%)		0/165 (0%)		0/110 (0%)
FOOT DEFORMITY	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
JOINT SWELLING	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
OSTEOARTHRITIS	1/156 (0.6%)		4/372 (1.1%)		0/165 (0%)		2/110 (1.8%)
RHEUMATOID ARTHRITIS	1/156 (0.6%)		19/372 (5.1%)		4/165 (2.4%)		4/110 (3.6%)
SPINAL OSTEOARTHRITIS	1/156 (0.6%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
LUMBAR SPINAL STENOSIS	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
MUSCULOSKELETAL CHEST PAIN	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
INTERVERTEBRAL DISC PROTRUSION	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		1/110 (0.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LEIOMYOMA	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
FIBROSARCOMA	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
BLADDER CANCER	1/156 (0.6%)		0/372 (0%)		0/165 (0%)		0/110 (0%)
UTERINE LEIOMYOMA	1/156 (0.6%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
BASAL CELL CARCINOMA	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		1/110 (0.9%)
BENIGN LUNG NEOPLASM	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
PITUITARY TUMOUR BENIGN	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
SQUAMOUS CELL CARCINOMA	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
MALIGNANT ANORECTAL NEOPLASM	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
BENIGN NEOPLASM OF THYROID GLAND	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
Nervous system disorders
SCIATICA	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
CEREBROVASCULAR ACCIDENT	1/156 (0.6%)		0/372 (0%)		0/165 (0%)		0/110 (0%)
Psychiatric disorders
DEPRESSION	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
Renal and urinary disorders
RENAL FAILURE	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
BLADDER PROLAPSE	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
RENAL IMPAIRMENT	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
STRESS URINARY INCONTINENCE	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
Reproductive system and breast disorders
OVARIAN CYST	0/156 (0%)		2/372 (0.5%)		0/165 (0%)		0/110 (0%)
DYSMENORRHOEA	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
UTERINE POLYP	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
OVARIAN TORSION	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
UTERINE PROLAPSE	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
Respiratory, thoracic and mediastinal disorders
HAEMOTHORAX	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
LARYNGEAL OEDEMA	0/156 (0%)		0/372 (0%)		0/165 (0%)		1/110 (0.9%)
LARYNGEAL GRANULOMA	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
RESPIRATORY FAILURE	0/156 (0%)		1/372 (0.3%)		1/165 (0.6%)		0/110 (0%)
SLEEP APNOEA SYNDROME	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		1/110 (0.9%)
ACUTE RESPIRATORY FAILURE	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
OBSTRUCTIVE AIRWAYS DISORDER	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
Skin and subcutaneous tissue disorders
PSORIASIS	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
URTICARIA	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
Vascular disorders
ARTERITIS	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
HAEMATOMA	0/156 (0%)		0/372 (0%)		1/165 (0.6%)		0/110 (0%)
VASCULITIS	1/156 (0.6%)		0/372 (0%)		0/165 (0%)		0/110 (0%)
HYPERTENSION	0/156 (0%)		1/372 (0.3%)		1/165 (0.6%)		0/110 (0%)
AORTIC STENOSIS	0/156 (0%)		1/372 (0.3%)		0/165 (0%)		0/110 (0%)
HYPERTENSIVE CRISIS	1/156 (0.6%)		0/372 (0%)		0/165 (0%)		0/110 (0%)
Other (Not Including Serious) Adverse Events
	ABA (DB)		ABA + MTX [OL]		INF + MTX [DB]		PLA + MTX [DB]
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	105/156 (67.3%)		285/372 (76.6%)		130/165 (78.8%)		82/110 (74.5%)
Gastrointestinal disorders
NAUSEA	16/156 (10.3%)		26/372 (7%)		21/165 (12.7%)		10/110 (9.1%)
VOMITING	5/156 (3.2%)		13/372 (3.5%)		10/165 (6.1%)		5/110 (4.5%)
DIARRHOEA	21/156 (13.5%)		56/372 (15.1%)		21/165 (12.7%)		7/110 (6.4%)
DYSPEPSIA	19/156 (12.2%)		41/372 (11%)		17/165 (10.3%)		7/110 (6.4%)
GASTRITIS	6/156 (3.8%)		22/372 (5.9%)		8/165 (4.8%)		7/110 (6.4%)
ABDOMINAL PAIN UPPER	3/156 (1.9%)		23/372 (6.2%)		8/165 (4.8%)		2/110 (1.8%)
General disorders
OEDEMA PERIPHERAL	8/156 (5.1%)		18/372 (4.8%)		6/165 (3.6%)		5/110 (4.5%)
Infections and infestations
INFLUENZA	13/156 (8.3%)		49/372 (13.2%)		12/165 (7.3%)		6/110 (5.5%)
SINUSITIS	10/156 (6.4%)		29/372 (7.8%)		7/165 (4.2%)		8/110 (7.3%)
BRONCHITIS	11/156 (7.1%)		41/372 (11%)		10/165 (6.1%)		11/110 (10%)
PHARYNGITIS	12/156 (7.7%)		43/372 (11.6%)		17/165 (10.3%)		9/110 (8.2%)
GASTROENTERITIS	4/156 (2.6%)		23/372 (6.2%)		12/165 (7.3%)		6/110 (5.5%)
NASOPHARYNGITIS	20/156 (12.8%)		69/372 (18.5%)		26/165 (15.8%)		15/110 (13.6%)
URINARY TRACT INFECTION	8/156 (5.1%)		67/372 (18%)		18/165 (10.9%)		13/110 (11.8%)
UPPER RESPIRATORY TRACT INFECTION	11/156 (7.1%)		50/372 (13.4%)		19/165 (11.5%)		16/110 (14.5%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	6/156 (3.8%)		9/372 (2.4%)		4/165 (2.4%)		6/110 (5.5%)
Musculoskeletal and connective tissue disorders
BACK PAIN	12/156 (7.7%)		41/372 (11%)		10/165 (6.1%)		8/110 (7.3%)
Nervous system disorders
HEADACHE	23/156 (14.7%)		54/372 (14.5%)		34/165 (20.6%)		24/110 (21.8%)
DIZZINESS	11/156 (7.1%)		25/372 (6.7%)		13/165 (7.9%)		7/110 (6.4%)
Psychiatric disorders
ANXIETY	5/156 (3.2%)		24/372 (6.5%)		7/165 (4.2%)		2/110 (1.8%)
INSOMNIA	5/156 (3.2%)		15/372 (4%)		12/165 (7.3%)		3/110 (2.7%)
DEPRESSION	6/156 (3.8%)		26/372 (7%)		6/165 (3.6%)		1/110 (0.9%)
Respiratory, thoracic and mediastinal disorders
COUGH	6/156 (3.8%)		28/372 (7.5%)		7/165 (4.2%)		5/110 (4.5%)
Skin and subcutaneous tissue disorders
RASH	1/156 (0.6%)		12/372 (3.2%)		10/165 (6.1%)		1/110 (0.9%)
PRURITUS	5/156 (3.2%)		5/372 (1.3%)		10/165 (6.1%)		1/110 (0.9%)
URTICARIA	3/156 (1.9%)		10/372 (2.7%)		11/165 (6.7%)		3/110 (2.7%)
Vascular disorders
HYPERTENSION	13/156 (8.3%)		42/372 (11.3%)		11/165 (6.7%)		13/110 (11.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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	BMS Study Director
Organization	Bristol-Myers Squibb
Phone
Email	Clinical.Trials@bms.com

Responsible Party:

Bristol-Myers Squibb

ClinicalTrials.gov Identifier:

NCT00095147

Other Study ID Numbers:

IM101-043

First Posted:

Nov 2, 2004

Last Update Posted:

Mar 24, 2015

Last Verified:

Mar 1, 2015