Double Blind Period (DB); Number of Participants Experiencing a New SLE Flare
SLE flares scored using BILAG:A:presence of =>1 serious;B:more moderate;C:mild symptomatic;D:prior activity,no current symptoms;E:organ that has never been involved. Calculated based on change during previous 4 weeks (1=improving,2=staying same,3=worsening,4=new).New SLE flare:first BILAG 'A' or 'B' event adjudicated to be flare following resolution of entry flare and start of prednisone/prednisone-equivalent taper.Inception treatment failure included (entry flare did not subside by Day 57/participant discontinued double-blind period before Day 29).
Open Label Period (OL); Number of Participants Who Died, Experienced Adverse Events (AEs), Serious AEs, Drug Related AEs or SAEs and Discontinued Due to AEs
AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to an AE were recorded. Drug-related AEs or SAEs: events with a relationship to the study therapy of certain; probable; possible; or missing.
OL; Number of Participants With Significant AEs of Special Interest
An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). For this study, it was decided that AEs of particular importance were associated with the use of immunomodulatory agents. Number of participants with infections, malignant Neoplasms, pre-specified autoimmune disorders, acute-infusional AEs and peri-infusional AEs were recorded.
OL; Number of Participants With Marked Abnormalities (MAs) in Hematology: Hemoglobin, Hematocrit, Erythrocytes and Platelet Count
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following hematology MA definitions specify the criteria for the data presented. Hemoglobin: >3 g/dL decrease from pre-treatment (pre-Rx) value; hematocrit: <0.75* pre-Rx value; erythrocyte count: <0.75* pre-Rx value; platelet count: <0.67* lower limit of normal (LLN) or >1.5* upper limit of normal (ULN) (or, if pre-Rx value <LLN, then <0.5* pre-Rx value or <100000/mm^3).
OL; Number of Participants With MAs in Hematology: Leukocytes, Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)
MMAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following hematology MA definitions specify the criteria for the data presented. Leukocytes: <0.75* LLN or >1.25* ULN (or, if pre-Rx value <LLN, then <0.8* pre-Rx or >ULN. If pre-Rx value >ULN, then >1.2* pre-Rx or <LLN; Neutrophils+bands (absolute): <1.00* 10^3 cells/microliter (c/uL); Lymphocytes (absolute): <0.75* 10^3 c/uL or >7.50* 10^3 c/uL; Monocytes (absolute): >2000/mm^3; Basophils (absolute): >0.40* 10^3 c/uL; Eosinophils (absolute): >0.75* 10^3 c/uL.
OL; Number of Participants With MAs in Serum Chemistry: Alkaline Phosphatase (ALP), Aspartate-aminotransferase (AST), Alanine-aminotransferase (ALT), Gamma-glutamyl Transferase (GGT), Bilirubin(Total), Blood Urea Nitrogen (BUN), Creatinine
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria. ALP, GGT: >2* ULN (if pre-Rx >ULN, then >3* pre-Rx); AST, ALT: >3* ULN (if pre-Rx >ULN, then >4* pre-Rx). Bilirubin (total): >2* ULN (if pre-Rx >ULN, then >4* pre-Rx), BUN:>2* pre-Rx; Creatinine:>1.5* pre-Rx.
OL; Number of Participants With MAs in Serum Chemistry: Sodium (Serum), Potassium (Serum), Chloride (Serum), Calcium (Total), Protein (Total)
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria, Sodium (serum): <0.95x LLN or >1.05x ULN (if pre-Rx<LLN, then <0.95x pre-Rx or >ULN. If pre-Rx >ULN, then >1.05x pre-Rx or <LLN); Potassium (serum), Chloride (serum), protein (total): <0.9x LLN or >1.1xULN (if pre-Rx <LLN, then <0.9xpre-Rx or >ULN. If pre-Rx >ULN, then >1.1xpre-Rx or <LLN; Calcium (total): <0.8xLLN or >1.2xULN (if pre-Rx <LLN, then <0.75x pre-Rx or >ULN. If pre-Rx >ULN, then >1.25x pre-Rx or <LLN.
OL; Number of Participants With MAs in Serum Chemistry: Glucose (Serum), Glucose (Fasting Serum), Albumin, Cholesterol (Total), Triglycerides, Fasting Triglycerides
MAs are laboratory measurements marked as abnormal, as per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria, Glucose: <65 mg/dL or >220 mg/dL; Glucose (fasting serum): <0.8* LLN or >1.5 ULN (if pre-Rx <LLN, then <0.8* pre-Rx or >ULN. If pre-Rx >ULN, then >2.0* pre-Rx or <LLN; Albumin: <0.9* LLN (if pre-Rx <LLN, then <0.75 * pre-Rx); cholesterol (total): >2* pre-Rx; triglycerides: >=2.5* ULN, or if pre Rx>ULN then use >2.5* pre Rx; fasting triglycerides: >=2.0* ULN, or if pre Rx>ULN then use >2.0* pre Rx.
OL; Number of Participants With MAs in Urinalysis
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following definitions specify the criteria for MAs in urinalysis, Protein, glucose, blood, Leukocyte esterase, red blood cells (RBC), white blood cells (WBC): >=2+ (or, if value >=4, or if pre-Rx value = 0 or 0.5, then >= 2* or if pre-Rx value =1, then >=3, or if pre-Rx = 2 or 3, then >=4); protein (24 hour urine): >1000 mg/24 hrs and >=2* pre-Rx; Glomerular filtration rate (GFR): <=60 mL/min/1.73m^2 or > 15% change from baseline; Protein/creatinine ratio: > 100 mg/mmol.
DB; Number of Participants With a New SLE Flare During the Initial 6 Months
SLE flares scored using BILAG:A:presence of =>1 serious;B:more moderate;C:mild symptomatic;D:prior activity,no current symptoms;E:organ that has never been involved.Calculated based on change during previous 4 weeks (1=improving,2=staying same,3=worsening,4=new).New SLE flare:first BILAG 'A' or 'B' event adjudicated to be flare following resolution of entry flare and/or start of prednisone/prednisone-equivalent taper.Inception treatment failure included (entry flare did not subside by Day 57/participant discontinued double-blind period before Day 29).
DB; Total Number of New SLE Flares Each Participant Experienced
SLE flares scored using BILAG:A:presence of =>1 serious;B:more moderate;C:mild symptomatic;D:prior activity,no current symptoms;E:organ that has never been involved.Calculated based on change during previous 4 weeks (1=improving,2=staying same,3=worsening,4=new).New SLE flare:BILAG 'A' or 'B' event adjudicated to be flare following resolution of entry flare and/or start of prednisone/prednisone-equivalent taper.Inception treatment failure included (entry flare did not subside by Day 57/participant discontinued double-blind period before Day 29).
DB; Median Number of Days to the First Occurrence of a New SLE Flare
Elapsed days between start of corticosteroid taper & first day of flare.Scored using BILAG:A:presence of =>1 serious;B:more moderate;C:mild symptomatic;D:prior activity,no current symptoms;E:organ that has never been involved.Calculated based on change during previous 4 weeks (1=improving,2=staying same,3=worsening,4=new).New SLE flare:first BILAG 'A' or 'B' event adjudicated to be flare following resolution of entry flare and/or start of corticosteroid taper.Inception treatment failure included (entry flare did not subside by Day 57/participant discontinued double-blind period before Day 29).
DB; Number of Participants With a Change in the SLICC/ACR Damage Index at 1 Year Compared to Baseline
SLICC/ACR score or damage index is a measure of cumulative damage due to Systemic Lupus Erythematosus (SLE). Damage is defined as non-reversible change (not related to active inflammation) occurring since onset of lupus, ascertained by clinical assessment and present for at least 6 months. A score of 0=no damage, early damage is defined as ≥1. The total maximum score is 48, and increasing score indicates increasing disease severity.
DB; Number of Participants Who Died, Experienced AEs, Other SAEs or Discontinuations Due to AEs, Drug Related AEs
AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Drug-related AEs: events with a certain; probable; possible; or missing relationship to the study therapy. Participants who discontinued the study due to an AE were recorded.
DB; Number of Participants With Significant AEs of Special Interest
An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). For this study, AEs of special interest were associated with the use of immunomodulatory agents. Number of participants with infections, malignant neoplasms, pre-specified autoimmune disorders, acute infusional AEs and peri-infusional AEs were recorded.
DB; Number of Participants With MAs in Hematology: Hemoglobin, Hematocrit, Erythrocytes and Platelet Count
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following hematology MA definitions specify the criteria for the data presented. Hemoglobin: >3 g/dL decrease from pre-treatment (pre-Rx) value; hematocrit: <0.75* pre-Rx value; erythrocyte count: <0.75* pre-Rx value; platelet count: <0.67* LLN or >1.5* ULN (or, if pre-Rx value <LLN, then <0.5* pre-Rx value or <100000/mm^3).
DB; Number of Participants With MAs in Hematology: Leukocytes, Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following hematology MA definitions specify the criteria for the data presented. Leukocytes: <0.75* LLN or >1.25* ULN (or, if pre-Rx value <LLN, then <0.8* pre-Rx or >ULN. If pre-Rx value >ULN, then >1.2* pre-Rx or <LLN; Neutrophils+bands (absolute): <1.00* 10^3 cells/microliter (c/uL); Lymphocytes (absolute): <0.75* 10^3 c/uL or >7.50* 10^3 c/uL; Monocytes (absolute): >2000/mm^3; Basophils (absolute): >0.40* 10^3 c/uL; Eosinophils (absolute): >0.75* 10^3 c/uL.
DB: Number of Participants With MAs in Serum Chemistry: ALP, AST, ALT, GGT, Bilirubin (Total), BUN and Creatinine
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria. ALP, GGT: >2* ULN (if pre-Rx >ULN, then >3* pre-Rx); AST, ALT: >3* ULN (if pre-Rx >ULN, then >4* pre-Rx). Bilirubin (total): >2* ULN (if pre-Rx >ULN, then >4* pre-Rx), BUN:>2* pre-Rx; Creatinine:>1.5* pre-Rx.
DB; Number of Participants With MAs in Serum Chemistry: Sodium (Serum), Potassium (Serum), Chloride (Serum), Calcium (Total),Protein (Total)
MAs are laboratory measurements marked as abnormal as per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria, Sodium (serum): <0.95* LLN or >1.05* ULN (if pre-Rx <LLN, then <0.95* pre-Rx or >ULN. If pre-Rx >ULN, then >1.05* pre-Rx or <LLN); Potassium (serum), Chloride (serum), protein (total): <0.9* LLN or >1.1* ULN (if pre-Rx <LLN, then <0.9* pre-Rx or >ULN. If pre-Rx >ULN, then >1.1* pre-Rx or <LLN; Calcium (total): <0.8* LLN or >1.2* ULN (if pre-Rx <LLN, then <0.75* pre-Rx or >ULN. If pre-Rx >ULN, then >1.25* pre-Rx or <LLN.
DB; Number of Participants With MAs in Serum Chemistry: Glucose (Serum), Glucose (Fasting Serum), Albumin, Cholesterol (Total), Triglycerides, Fasting Triglycerides
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria, Glucose: <65 mg/dl or >220 mg/dl; Glucose (fasting serum): <0.8* LLN or >1.5 ULN (if pre-Rx <LLN, then <0.8* pre-Rx or >ULN. If pre-Rx >ULN, then >2.0* pre-Rx or <LLN; Albumin: <0.9* LLN (if pre-Rx <LLN, then <0.75 * pre-Rx); cholesterol (total): >2* pre-Rx; triglycerides: >=2.5* ULN, or if pre Rx>ULN then use >2.5* pre Rx; fasting triglycerides: >=2.0* ULN, or if pre Rx>ULN then use >2.0* pre Rx.
DB; Number of Participants With MAs in Urinalysis
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following definitions specify the criteria for MAs in urinalysis, Protein, glucose, blood, Leukocyte esterase, RBC, WBC: >=2+ (or, if value >=4, or if pre-Rx value = 0 or 0.5, then >= 2* pre-Rx, or if pre-Rx value =1, then >=3, or if pre-Rx = 2 or 3, then >=4); protein (24 hour urine): >1000 mg/24 hrs and >=2* pre-Rx; GFR: <=60 mL/min/1.73m^2 or > 15% change from baseline; Protein/creatinine ratio: > 100 mg/mmol.
DB; Number of Participants With Clinically Significant Abnormal Vital Signs and/or Physical Examination Findings
Vital signs assessments and physical examination were conducted throughout the study. Vital signs assessments included body temperature, respiratory rate, blood pressure (systolic and diastolic) and heart rate. The investigator used his/her clinical judgment to decide whether or not abnormalities in vital signs or physical examination were clinically meaningful.
DB; Number of Participants With Antibodies Specific for CTLA4-T and Abatacept, Following Abatacept Treatment
Electrochemiluminescence (ECL) immunoassay based on Meso Scale Discovery (MSD) technology was used to detect antibodies specific for CTLA4-T and for abatacept.
OL; Number of Participants With a New SLE Flare
SLE flares scored using BILAG:A:presence of =>1 serious lupus features;B:more moderate features;C:mild symptomatic features;D:prior activity with no current symptoms due to active lupus;E:an organ that has never been involved.BILAG scores based on degrees of change in clinical features (1=improving,2=staying the same,3=worsening,4=new).New SLE flare means new BILAG A/B features in any organ system.Based on the recommendation of the Data Monitoring Committee, open-label period terminated, as failed to meet primary outcome measure for double-blind period/increase in SAEs in abatacept group.
OL; Number of Participants With a Change in the SLICC/ACR Damage Index at Year 2 Compared to Baseline
SLICC/ACR damage index:measure of cumulative damage due to SLE.Damage=non-reversible change occurring since onset of lupus,ascertained by clinical assessment & present for =>6 months.Scores of SLICC/ACR index:1:single episode;2:repeated episodes at least 6 months apart.Change in score from baseline to 1 year presented as:no change,increase 1 (an increase in score of 1),increase >1 (an increase in score of >1).Based on recommendation of Data Monitoring Committee, open-label period terminated, as failed to meet primary outcome measure for double-blind period/increase in SAEs in abatacept group.
OL; Total Number of BILAG A Flares Each Participant Experienced
Total number of BILAG A flares in any organ system after steroid tapering = new BILAG A features in any organ system. Scores defined as follows: None: participants with no BILAG A flare; 1: participants with 1 BILAG A flare or participants who discontinued without a new BILAG A flare were imputed as having one event. 2: participants with 2 BILAG A flares; 3 or >3: participants with 3 or more BILAG A flares.Based on recommendation of Data Monitoring Committee, open-label period terminated, as failed to meet primary outcome measure for double-blind period/increase in SAEs in abatacept group.
OL; Area Under the Curve (AUC) for Prednisone or Prednisone Equivalent
Total exposure to glucocorticosteroid was measured by the total prednisone or prednisone equivalent AUC. Based on the recommendation of the Data Monitoring Committee, the open-label, long-term extension period was terminated by the sponsor, for failure to meet the primary outcome measure for the double-blind period and because of an increase in SAEs in the abatacept treatment group. As such, these data were not analyzed.
OL; Number of Participants With Antibodies Specific for CTLA4-T and Abatacept, Following Abatacept Treatment
MSD technology was used to detect antibodies specific for CTLA4-T and for abatacept.