• Double Blind Period (DB); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation [ Time Frame: Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication ] [ Designated as safety issue: Yes ]
  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. Related SAE/AE = possibly, probably, or certainly related to study drug
  
  
• DB; Number of Participants With AEs of Special Interest [ Time Frame: Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication ] [ Designated as safety issue: Yes ]
  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, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).
  
  
• DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria [ Time Frame: Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication ] [ Designated as safety issue: Yes ]
  Upper Normal Limit (ULN), Lower Normal Limit (LLN), Baseline (BL). Marked abnormality criteria are: Hemoglobin (HGB): >3 g/dL decrease from BL; Hematocrit: <0.75 * BL; Erythrocytes: <0.75 * BL; Platelets (PLT): <0.67 * LLN/>1.5 * ULN, or if BL < LLN then use <0.5 * BL and <100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL<LLN then use <0.8 * BL or >ULN, or if BL>ULN then use >1.2 * BL or <LLN; neutrophils+bands: <1.0 * 10^3 c/uL; eosinophils: >0.750 * 10^3 c/uL; basophils: > 400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750 * 10^3 c/uL/ >7.50 * 10^3 c/uL.
  
  
• DB; Number of Participants With Blood Chemistry Laboratories Meeting Marked Abnormality (MA) Criteria [ Time Frame: Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication ] [ Designated as safety issue: Yes ]
  ULN=upper level of normal; BL=baseline.Marked abnormality criteria: High alkaline phosphatase (ALP): >2* ULN, or if BL>ULN then use >3* BL; high aspartate aminotransferase (AST): >3* ULN (80 U/L), or if BL>ULN then use >4* BL; high alanine aminotransferase (ALT): >3* ULN (34-47 U/L), or if BL>ULN then use >4* BL; high G-Glutamyl transferase (GGT): >2* ULN, or if BL>ULN then use >3* BL; high bilirubin: >2* ULN, or if BL>ULN then use >4* BL; high blood urea nitrogen (BUN): >2* BL; high creatinine: >1.5* BL (ULN 14.6 pg/mg. AST ULN=80 U/L; ALT ULN=34-47 U/L;creatinine ULN=14.6 pg/mg.
  
  
• DB; Number of Participants With Clinically Significant Physical Examination or Vital Signs Abnormalities [ Time Frame: Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337. Vital signs were measured at these visits before and after study medication infusion. ] [ Designated as safety issue: Yes ]
  Physical examinations were performed at the discretion of the investigator and included breast examinations for female participants. Vital sign measurements were performed for participants before and after infusion of study medication at each visit and included seated systolic blood pressure, seated diastolic blood pressure, temperature, and heart rate. Abnormalities were determined to be clinically significant by the investigator.
  
  
• Open Label Period (OL); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation [ Time Frame: Day 365 to Day 1,821 ] [ Designated as safety issue: Yes ]
  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. Related SAE/AE = possibly, probably, or certainly related to study drug
  
  
• OL; Number of Participants With AEs of Special Interest [ Time Frame: Day 365 to Day 1821 ] [ Designated as safety issue: Yes ]
  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, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).
  
  
• OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria [ Time Frame: Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication ] [ Designated as safety issue: Yes ]
  Upper Normal Limit (ULN), Lower Normal Limit (LLN), Baseline (BL). Marked abnormality criteria are: Hemoglobin (HGB): >3 g/dL decrease from BL; Hematocrit: <0.75 * BL; Erythrocytes: <0.75 * BL; Platelets (PLT): <0.67 * LLN/>1.5 * ULN, or if BL < LLN then use <0.5 * BL and <100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL<LLN then use <0.8 * BL or >ULN, or if BL>ULN then use >1.2 * BL or <LLN; neutrophils+bands: <1.0 * 10^3 c/uL; eosinophils: >0.750 * 10^3 c/uL; basophils: > 400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750 * 10^3 c/uL/ >7.50 * 10^3 c/uL.
  
  
• OL; Number of Participants With Liver Function Laboratories Meeting Marked Abnormality Criteria [ Time Frame: Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication ] [ Designated as safety issue: Yes ]
  Marked abnormality criteria: Alkaline phosphatase (ALP): >2* ULN, or if BL>ULN then use >3* BL; aspartate aminotransferase (AST): >3* ULN, or if BL>ULN then use >4* BL; alanine aminotransferase (ALT): >3* ULN, or if BL>ULN then use >4* BL; G-Glutamyl transferase (GGT): >2* ULN, or if BL>ULN then use >3* BL; Bilirubin: >2* ULN, or if BL>ULN then use >4* BL; blood urea nitrogen (BUN): >2* BL; creatinine: >1.5* BL
  
  
• OL; Number of Participants With Electrolyte Laboratories Meeting Marked Abnormality Criteria [ Time Frame: Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication ] [ Designated as safety issue: Yes ]
  Marked abnormality criteria: Sodium (Na): <0.95*LLN/ >1.05*ULN, or if BL<LLN then use <0.95* BL or >ULN, or if BL>ULN then use>1.05* BL or <LLN; potassium (K): <0.9* LLN/>1.1*ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; (Cl): <0.9* LLN/>1.1* ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; calcium (Ca): <0.8* LLN/>1.2* ULN, or if BL<LLN then use <0.75* BL or >ULN, or if BL>ULN then use>1.25* BL or <LLN; phosphorous (P): <0.75* LLN/ >1.25* ULN, or if BL<LLN then use 0.67* BL or >ULN, or if BL>ULN then use>1.33* BL or <LLN
  
  
• OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria [ Time Frame: Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication ] [ Designated as safety issue: Yes ]
  MA criteria: serum glucose (Glu): <65 mg/dL/>220 mg/dL;fasting serum Glu: <0.8* LLN/>1.5*ULN,or if BL<LLN then use 0.8*BL or >ULN,or if BL>ULN then use >2.0*BL or <LLN;total protein: <0.9*LLN/>1.1*ULN,or if BL<LLN then use <0.9*BL or >UNL,or if BL>UNL then use >1.1*BL or <LLN; albumin: <0.9*LLN,or if BL<LLN then use <0.75 BL;uric acid: >1.5*ULN,or if BL>ULN then use >2*BL. Urinalysis (Urine protein,urine Glu,urine blood,leukocyte esterase,Red Blood Cells [RBCs], White Blood Cells [WBCs]):Use ≥2 when BL value missing or when pre-dose=0 or 0.5; use ≥3 when pre-dose=1, use ≥4 when pre-dose=2 or 3
  
  
• OL; Number of Participants With Clinically Significant Physical Examination or Vital Signs Abnormalities [ Time Frame: Days 365 to Day 1821 ] [ Designated as safety issue: Yes ]
  Physical examinations were performed at the discretion of the investigator and included breast examinations for female participants. Vital sign measurements were performed for participants before and after infusion of study medication at each visit and included seated systolic blood pressure, seated diastolic blood pressure, temperature, and heart rate. Abnormalities were determined to be clinically significant by the investigator.
  
  

• DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by Enzyme-Linked Immunosorbant Assay (ELISA) [ Time Frame: Days 1, 29, 57, 85, 113,169, 281, 365 ] [ Designated as safety issue: Yes ]
  Serum samples from all treated adult participants with active rheumatoid arthritis (RA) were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.
  
  
• DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by ELISA [ Time Frame: Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337 ] [ Designated as safety issue: Yes ]
  Serum samples from all treated adult participants with active rheumatoid arthritis were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.
  
  

This was a multinational, multicenter, randomized, double-blind, 2-arm, parallel-dosing designed study. The treatment period was 12 months. Eligible participants were randomized to 1 of 2 treatment groups: abatacept fixed dose approximating 10 mg/kg (based on participant's body weight; 500 mg for participants weighing < 60kg; 750 mg for participants weighing 60 to 100 kg; and 1 gram for participants weighing > 100 kg, monthly) or placebo intravenous (IV) infusion. All participants continued their background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs [DMARDs], or combination) throughout the double-blind treatment period. Double-blind study medication (abatacept or placebo) was administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses.

All participants who completed the 12-month double-blind study period (Day 1 through Day 365), were eligible to continue into the open-label period. All eligible participants (active or placebo) were re-allocated to receive abatacept at a weight-tiered dose that approximated 10 mg/kg, based on their Day 365 body weight. Participants continued to receive infusions every 28 days.