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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00095147
• Other study ID #: IM101-043
• Status: Completed
• Phase: Phase 3
• First received: November 1, 2004
• Last updated: March 4, 2015
• Start date: February 2005
• Est. completion date: July 2009

Study information

• Verified date: March 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 431
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Abatacept (ABA) + Methotrexate (MTX), double-blind (DB)
Abatacept, intravenous (IV) Solution, Infusion, Depends on participant weight, Monthly, 12 months.
• Infliximab (INF) + MTX, DB
Infliximab, IV Solution, Infusion, Depends on participant weight, Every 2 Months, 12 months.
• Placebo (PLA) + MTX, DB
Placebo, IV Solution, Infusion, Depends on participant weight, Monthly, 6 months.
• 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
• ABA, open-label (OL)
Abatacept, IV solution, Infusion. Depends on participant weight, Monthly, 12+ months

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Quilmes	Buenos Aires
Argentina	Local Institution	Tucuman
Australia	Local Institution	Cairns	Queensland
Australia	Local Institution	Clayton	Victoria
Australia	Local Institution	Cotton Tree	Queensland
Australia	Local Institution	Heidelberg	Victoria
Australia	Local Institution	Malvern	Victoria
Australia	Local Institution	Parkville	Victoria
Australia	Local Institution	Perth	Western Australia
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Recife	Pernambuco
Brazil	Local Institution	Rio De Janeiro
Brazil	Local Institution	Sao Paulo
Canada	Local Institution	Calgary	Alberta
Canada	Local Institution	Edmonton	Alberta
Canada	Local Institution	Hamilton	Ontario
Canada	Local Institution	Kitchener	Ontario
Canada	Local Institution	Kitchener
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Ottawa	Ontario
Canada	Local Institution	Saskatoon	Saskatchewan
Canada	Local Institution	St. Johns	Newfoundland and Labrador
Canada	Local Institution	Ste-Foy	Quebec
Canada	Local Institution	Winnipeg	Manitoba
Czech Republic	Local Institution	Prague 2
Denmark	Local Institution	Copenhagen
Korea, Republic of	Local Institution	Seoul
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Leon	Guanajuato
Mexico	Local Institution	Mexico	Distrito Federal
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	San Luis Potosi
Mexico	Local Institution	Tijuana	Baja California
Peru	Local Institution	Lima
Poland	Local Institution	Poznan
Poland	Local Institution	Sopot
Poland	Local Institution	Warszawa
Puerto Rico	Local Institution	Rio Piedras
Russian Federation	Local Institution	Moscow
South Africa	Local Institution	Berea	Kwa Zulu Natal
South Africa	Local Institution	Muckleneuk	Gauteng
South Africa	Local Institution	Panorama	Western Cape
Spain	Local Institution	A Coruna
Spain	Local Institution	Barcelona
Spain	Local Institution	Cordoba
Spain	Local Institution	Madrid
Sweden	Local Institution	Falun
Sweden	Local Institution	Linkoping
Sweden	Local Institution	Lund
Sweden	Local Institution	Stockholm
Sweden	Local Institution	Uppsala
Switzerland	Local Institution	Bern
Switzerland	Local Institution	St. Gallen
United States	Local Institution	Austin	Texas
United States	Local Institution	Bethlehem	Pennsylvania
United States	Local Institution	Boca Raton	Florida
United States	Local Institution	Charlotte	North Carolina
United States	Local Institution	Cincinnati	Ohio
United States	Local Institution	Dallas	Texas
United States	Local Institution	Denver	Colorado
United States	Local Institution	Flowood	Mississippi
United States	Local Institution	Ft Lauderdale	Florida
United States	Local Institution	Huntsville	Alabama
United States	Local Institution	Indianapolis	Indiana
United States	Local Institution	Largo	Florida
United States	Local Institution	New Orleans	Louisiana
United States	Local Institution	Oklahoma City	Oklahoma
United States	Local Institution	Springfield	Massachusetts
United States	Local Institution	Syracuse	New York
United States	Local Institution	Tulsa	Oklahoma
United States	Local Institution	Willow Grove	Pennsylvania
United States	Local Institution	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Czech Republic,  Denmark,  Korea, Republic of,  Mexico,  Peru,  Poland,  Puerto Rico,  Russian Federation,  South Africa,  Spain,  Sweden,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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.	Baseline (Day 1), 6 months (Day 197)	No
Primary	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	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.	From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)	Yes
Primary	OL; Number of Participants With AEs of Special Interest	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).	From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)	Yes
Primary	OL; Number of Participants With Select Hematologic Laboratory Abnormalities	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;	From Day 366 through end of OL (range from 1.9 months to 42.3 months)	Yes
Primary	OL; Number of Participants With Select Blood Chemistry Laboratory Abnormalities	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	From Day 366 through end of OL (range from 1.9 months to 42.3 months)	Yes
Primary	OL; Mean Change From Baseline to Day 365 in Hemoglobin, Total Protein, and Albumin	Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN	Baseline (Day 1), Day 365	Yes
Primary	OL; Mean Change From Baseline to Day 365 in Platelets	Platelets (PLT): <0.67 x LLN, >1.5 x ULN	Baseline (Day 1), Day 365	Yes
Primary	OL; Mean Change From Baseline to Day 365 in Hematocrit	Hematocrit: <0.75 x BL	Baseline (Day 1), Day 365	Yes
Primary	OL; Mean Change From Baseline to Day 365 in White Blood Cells	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.	Baseline (Day 1), Day 365	Yes
Primary	OL; Mean Change From Baseline to Day 365 in Erythrocytes	Erythrocytes: <0.75 x BL	Baseline (Day 1), Day 365	Yes
Primary	OL; Mean Change From Baseline to Day 365 in Electrolytes	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	Baseline (Day 1), Day 365	Yes
Primary	OL; Mean Change From Baseline to Day 365 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid	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;	Baseline (Day 1), Day 365	Yes
Primary	OL; Mean Change From Baseline to Day 365 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase	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	Baseline (Day 1), Day 365	Yes
Primary	OL; Mean Change From Baseline to Day 729 in Hemoglobin, Total Protein, and Albumin	Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN	Baseline (Day 1), Day 729	Yes
Primary	OL; Mean Change From Baseline to Day 729 in Platelets	Platelets (PLT): <0.67 x LLN, >1.5 x ULN	Baseline (Day 1), Day 729	Yes
Primary	OL; Mean Change From Baseline to Day 729 in Hematocrit	Hematocrit: <0.75 x BL	Baseline (Day 1), Day 729	Yes
Primary	OL; Mean Change From Baseline to Day 729 in White Blood Cells	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.	Baseline (Day 1), Day 729	Yes
Primary	OL; Mean Change From Baseline to Day 729 in Erythrocytes	Erythrocytes: <0.75 x BL	Baseline (Day 1), Day 729	Yes
Primary	OL; Mean Change From Baseline to Day 729 in Electrolytes	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	Baseline (Day 1), Day 729	Yes
Primary	OL; Mean Change From Baseline to Day 729 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid	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;	Baseline (Day 1), Day 729	Yes
Primary	OL; Mean Change From Baseline to Day 729 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase	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	Baseline (Day 1), Day 729	Yes
Primary	OL; Mean Change From Baseline to Day 1121 in Hemoglobin, Total Protein, and Albumin	Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN	Baseline (Day 1), Day 1121	Yes
Primary	OL; Mean Change From Baseline to Day 1121 in Platelets	Platelets (PLT): <0.67 x LLN, >1.5 x ULN	Baseline (Day 1), Day 1121	Yes
Primary	OL; Mean Change From Baseline to Day 1121 in Hematocrit	Hematocrit: <0.75 x BL	Baseline (Day 1), Day 1121	Yes
Primary	OL; Mean Change From Baseline to Day 1121 in White Blood Cells	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.	Baseline (Day 1), Day 1121	Yes
Primary	OL; Mean Change From Baseline to Day 1121 in Erythrocytes	Erythrocytes: <0.75 x BL	Baseline (Day 1), Day 1121	Yes
Primary	OL; Mean Change From Baseline to Day 1121 in Electrolytes	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	Baseline (Day 1), Day 1121	Yes
Primary	OL; Mean Change From Baseline to Day 1121 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid	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;	Baseline (Day 1), Day 1121	Yes
Primary	OL; Mean Change From Baseline to Day 1121 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase	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	Baseline (Day 1), Day 1121	Yes
Primary	OL; Mean Change From Baseline to Day 1513 in Hemoglobin, Total Protein, and Albumin	Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN	Baseline (Day 1), Day 1513	Yes
Primary	OL; Mean Change From Baseline to Day 1513 in Platelets	Platelets (PLT): <0.67 x LLN, >1.5 x ULN	Baseline (Day 1), Day 1513	Yes
Primary	OL; Mean Change From Baseline to Day 1513 in Hematocrit	Hematocrit: <0.75 x BL	Baseline (Day 1), Day 1513	Yes
Primary	OL; Mean Change From Baseline to Day 1513 in White Blood Cells	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.	Baseline (Day 1), Day 1513	Yes
Primary	OL; Mean Change From Baseline to Day 1513 in Erythrocytes	Erythrocytes: <0.75 x BL	Baseline (Day 1), Day 1513	Yes
Primary	OL; Mean Change From Baseline to Day 1513 in Electrolytes	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	Baseline (Day 1), Day 1513	Yes
Primary	OL; Mean Change From Baseline to Day 1513 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid	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;	Baseline (Day 1), Day 1513	Yes
Primary	OL; Mean Change From Baseline to Day 1513 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase	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	Baseline (Day 1), Day 1513	Yes
Primary	OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period	Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP), units=mm mercury (Hg)	Days 365, 729, 1121, and 1513	Yes
Primary	OL; Mean Heart Rate (HR) During Open Label Period	Heart Rate (HR), units=beats per minute (bpm)	Days 365, 729, 1121, and 1513	Yes
Primary	OL; Mean Temperature (T) During Open Label Period	Temperature (T), units=degrees Celcius	Days 365, 729, 1121, and 1513	Yes
Secondary	DB; Adjusted Mean Change From Baseline to Day 197 in DAS 28 Score (ESR) For INF Versus PLA (LOCF Analysis)	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.	Baseline (Day 1), 6 months (Day 197)	No
Secondary	DB; DAS 28 (ESR) Area Under The Curve (AUC) Over 12 Months For ABA Versus INF	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.	From Day 1 through Day 365 (12 months)	No
Secondary	DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at 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 Day 197	No
Secondary	DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at 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 Day 365	No
Secondary	DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis)	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.	Baseline (Day 1), 6 months (Day 197)	No
Secondary	DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis)	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.	Baseline (Day 1), 12 months (Day 365)	No
Secondary	DB; Adjusted Mean Change From Baseline to Day 197 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)	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.	Baseline (Day 1), 6 months (Day 197)	No
Secondary	DB; Adjusted Mean Change From Baseline to Day 365 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)	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.	Baseline (Day 1), 12 months (Day 365)	No
Secondary	DB; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) at 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 Day 365	No
Secondary	DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at 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 Day 197	No
Secondary	DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at 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 Day 365	No
Secondary	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	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.	From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study	Yes
Secondary	DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 197	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).	From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study	Yes
Secondary	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	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.	From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study	Yes
Secondary	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	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.	From Day 198 through Day 365, and up to 56 days after last dose if occurring on-study	Yes
Secondary	DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 365	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).	From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study	Yes
Secondary	DB; Number of Participants With AEs of Special Interest From Day 198 Through Day 365 in Participants Receiving Placebo Switched to Abatacept	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).	From Day 198 through Day 365, and up to 56 days after last dose if occurring on-study	Yes
Secondary	DB; Number of Participants With Significant Changes in Mean Systolic and Diastolic Blood Pressure During Days 1 Through 197 and Days 1 Through 365	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.	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	Yes
Secondary	DB; Number of Participants With Significant Changes in Mean Heart Rate During Days 1 Through 197 and Days 1 Through 365	Heart Rate (HR) was assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.	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	Yes
Secondary	DB; Number of Participants With Significant Changes in Mean Temperature During Days 1 Through 197 and Days 1 Through 365	Temperature (T) was assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.	From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study	Yes
Secondary	DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197	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	From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study	Yes
Secondary	DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365	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	From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study	Yes
Secondary	DB; Number of Participants With Anti-Abatacept Antibodies From Day 1 Through Day 365 (Electrochemiluminescent [ECL] Immunoassay)	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.	Day 1 through day 365	No
Secondary	DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From 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.	Day 1 through day 365	No
Secondary	OL; Mean Change From Baseline Over Time in DAS 28 (ESR) Score	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.	Baseline (Day 1), Day 365, Day 533, Day 729	No
Secondary	OL; Percentage of Participants With DAS28 (ESR) Remission and Low Disease Activity (LDAS) Over Time	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.	Baseline (Day 1), Day 365, Day 533, Day 729	No
Secondary	OL; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Over Time	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 Days 365, 533, and 729	No
Secondary	OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time	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 Day 197, Day 365, Day 533, Day 729	No
Secondary	OL; Percentage of Participants Who Achieved Major Clinical Response	Major Clinical Response was defined as a continuous ACR 70 for six months.	Defined from the date of achieving ACR 70 response to 6 months post response	No
Secondary	OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time	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 Days 197, 253, 281, 309, 337, 365, 449, 533, 617, and 729	No
Secondary	OL; Adjusted Mean Change From Baseline to Day 729 in HAQ-DI	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.	Day 1 (Baseline), Day 729	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm