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

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)

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

Erythrocytes: \<0.75 x BL

Time frame: Baseline (Day 1), Day 1121

Population: 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.

Hematocrit: \<0.75 x BL

Time frame: Baseline (Day 1), Day 1121

Population: 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.

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

Population: 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.

Platelets (PLT): \<0.67 x LLN, \>1.5 x ULN

Time frame: Baseline (Day 1), Day 1121

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

Erythrocytes: \<0.75 x BL

Time frame: Baseline (Day 1), Day 1513

Population: 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.

Hematocrit: \<0.75 x BL

Time frame: Baseline (Day 1), Day 1513

Population: 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.

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

Population: 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.

Platelets (PLT): \<0.67 x LLN, \>1.5 x ULN

Time frame: Baseline (Day 1), Day 1513

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

Erythrocytes: \<0.75 x BL

Time frame: Baseline (Day 1), Day 365

Population: 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.

Hematocrit: \<0.75 x BL

Time frame: Baseline (Day 1), Day 365

Population: 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.

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

Population: 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.

Platelets (PLT): \<0.67 x LLN, \>1.5 x ULN

Time frame: Baseline (Day 1), Day 365

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

Erythrocytes: \<0.75 x BL

Time frame: Baseline (Day 1), Day 729

Population: 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.

Hematocrit: \<0.75 x BL

Time frame: Baseline (Day 1), Day 729

Population: 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.

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

Population: 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.

Platelets (PLT): \<0.67 x LLN, \>1.5 x ULN

Time frame: Baseline (Day 1), Day 729

Population: 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.

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

Population: 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.

Heart Rate (HR), units=beats per minute (bpm)

Time frame: Days 365, 729, 1121, and 1513

Population: 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.

Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP), units=mm mercury (Hg)

Time frame: Days 365, 729, 1121, and 1513

Population: 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.

Temperature (T), units=degrees Celcius

Time frame: Days 365, 729, 1121, and 1513

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: As Treated Population.

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

Population: As-Treated Population

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

Population: As Treated Population.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.