Study of Abatacept (BMS-188667) in Subjects With Active Rheumatoid Arthritis on Background Non-biologic DMARDS (Disease Modifying Antirheumatic Drugs) Who Have an Inadequate Response to Anti-TNF Therapy - Full Text View

Sponsor:	Bristol-Myers Squibb
Information provided by (Responsible Party):	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00124982

Purpose

The purpose of this study is to summarize the safety and tolerability of abatacept during 6 months of combined treatment with one or more of the background non-biologic disease modifying anti-rheumatic drugs (DMARDs) approved for rheumatoid arthritis (RA) in subjects with active RA. Secondary objectives assessed the clinical efficacy of combination treatment, including disease activity, physical function, and quality of life outcomes.

Condition	Intervention	Phase
Rheumatoid Arthritis	Drug: Abatacept Drug: Non-biologic Disease Modifying Anti-Rheumatic Drug (DMARD) Drug: Anti-Tumor Necrosing Factor (TNF) Therapy	Phase III

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase III, Multi-Center, Open Label Study to Evaluate the Efficacy, Tolerability and Safety of Abatacept (BMS-188667) in Subjects With Active Rheumatoid Arthritis on Background Non-Biologic DMARDs Who Have an Inadequate Response to Anti-TNF Therapy and Have Limited Therapeutic Options

Resource links provided by NLM:

MedlinePlus related topics: Potassium Rheumatoid Arthritis

Drug Information available for: Abatacept

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

Short-term Period: Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuations, AEs, Related AEs, or AEs Leading to Discontinuations [ Time Frame: Days 1-169 ] [ 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 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 AE/SAE=Certain,Probable,Possible,or Missing relationship to Drug
Short-term Period: Number of Participants With AEs of Special Interest [ Time Frame: Days 1-169 ] [ 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).
Short-term Period: Number of Participants With Hematology Laboratories Meeting Marked Abnormality (MA) Criteria [ Time Frame: Days 1-169 ] [ 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/<100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL<LLN then use <0.8 * BL/>ULN, or if BL>ULN then use >1.2 * BL/<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.
Short-term Period: Number of Participants With Liver and Kidney Function Laboratories Meeting MA Criteria [ Time Frame: Days 1-169 ] [ 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
Short-term Period: Number of Participants With Electrolyte Laboratories Meeting MA Criteria [ Time Frame: Days 1-169 ] [ 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; chloride: <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
Short-term Period: Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting MA Criteria [ Time Frame: Days 1-169 ] [ Designated as safety issue: Yes ]
Marked abnormality 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; 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 value ≥4,or when pre-dose=0 or 0.5. Use ≥3 when pre-dose=1. Use ≥4 when pre-dose=2 or 3
Short-term Period: Mean Change From Baseline in Systolic and Diastolic Blood Pressure [ Time Frame: Day 1 (Baseline) -Day 169 ] [ Designated as safety issue: Yes ]
Short-term Period: 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 1-169 ] [ 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.
Long-term Period: Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuations, AEs, Related AEs, or AEs Leading to Discontinuations [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ] [ 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 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 AE/SAE=Certain,Probable,Possible,or Missing relationship to Drug
Long-term Period: Number of Participants With AEs of Special Interest [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ] [ 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).
Long-term Period: Number of Participants With Hematology Laboratories Meeting Marked Abnormality (MA) Criteria [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ] [ Designated as safety issue: Yes ]
ULN=upper limit of normal; LLN=lower limit of normal; BL=baseline. Marked abnormality criteria=Hemoglobin: >3 g/dL decrease from BL; Hematocrit: <0.75*BL; Erythrocytes:<0.75*BL; Platelets: <0.67*LLN/>1.5 * ULN, or if BL<LLN, use 0.5*BL/<100,000 mm^3; Leukocytes: <0.75*LLN/>1.25*ULN, or if BL<LLN, use <0.8*BL/>ULN, or if BL>ULN,use >1.2*BL/<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.
Long-term Period: Number of Participants With Liver and Kidney Function Laboratories Meeting MA Criteria [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ] [ Designated as safety issue: Yes ]
Marked abnormality criteria: Alkaline phosphatase (ALP): >2*ULN, or if BL>ULN, use >3*BL; aspartate aminotransferase (AST): >3*ULN, or if BL>ULN,use >4*BL; alanine aminotransferase (ALT): >3*ULN, or if BL>ULN, use >4*BL; G-Glutamyl transferase (GGT): >2*ULN, or if BL>ULN, use >3*BL; bilirubin: >2*ULN, or if BL>ULN, use >4*BL; blood urea nitrogen (BUN): >2*BL; creatinine: >1.5*BL
Long-term Period: Number of Participants With Electrolyte Laboratories Meeting MA Criteria [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ] [ 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; chloride: <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
Long-term Period: Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting MA Criteria [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ] [ Designated as safety issue: Yes ]
Marked abnormality 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; 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 value ≥4,or when pre-dose=0 or 0.5. Use ≥3 when pre-dose=1. Use ≥4 when pre-dose=2 or 3
Long-term Period: Change From Baseline in Hemoglobin (HGB), Total Protein, and Albumin Over Time [ Time Frame: BL, Day 365, Day 729 ] [ Designated as safety issue: Yes ]
HGB normal range (NR)=11.6 - 16.2 g/dL, marked abnormality (MA) is >3 g/dL decrease from BL. Total protein NR=6.0 - 8.4 g/dL, MA is <0.9* LLN/>1.1* ULN; Albumin NR=3.5 - 5.3 g/dL, MA is <0.9* LLN, or if BL<LLN then use <0.75 BL
Long-term Period: Change From Baseline in Hematocrit Over Time [ Time Frame: BL, Day 365, Day 729 ] [ Designated as safety issue: Yes ]
The hematocrit value refers to the percentage of blood volume that is occupied by red blood cells. Hematocrit values for participants were expressed as percentages and were averaged to yield a group mean value (percentage) at a particular time point. The mean change from baseline in hematocrit value (expressed as a percent)= mean post-baseline value (expressed as a percent) - mean baseline value (expressed as a percent).
Long-term Period: Change From Baseline in Erythrocytes Over Time [ Time Frame: BL, Day 365, Day 729 ] [ Designated as safety issue: Yes ]
Erythrocytes NR= 3.80 - 5.50 *10^6 c/uL, MA is <0.75 * BL
Long-term Period: Change From Baseline in Platelets (PLT) Over Time [ Time Frame: BL, Day 365, Day 729 ] [ Designated as safety issue: Yes ]
Erythrocytes NR= 3.80 - 5.50 *10^6 c/uL, MA is <0.75 * BL
Long-term Period: Change From Baseline in White Blood Cells Over Time [ Time Frame: BL, Day 365, Day 729 ] [ Designated as safety issue: Yes ]
Leukocytes NR=4.1 - 12.3*10^3 c/uL, MA is <0.75 * LLN/ >1.25 * ULN, or if BL<LLN then use <0.8 * BL/>ULN, or if BL>ULN then use >1.2 * BL/<LLN. Neutrophils+bands MA is <1.0 * 10^3 c/uL. Eosinophils MA is >0.750 * 10^3 c/uL. Basophils MA is > 400 mm^3. Monocytes MA is >2000 mm^3. Lymphocytes MA is <0.750 * 10^3 c/uL/ >7.50 * 10^3 c/uL
Long-term Period: Change From Baseline in Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and G-Glutamyl Transferase (GGT) Over Time [ Time Frame: BL, Day 365, Day 729 ] [ Designated as safety issue: Yes ]
HGB normal range (NR)=11.6 - 16.2 g/dL, marked abnormality (MA) is >3 g/dL decrease from BL. Total protein NR=6.0 - 8.4 g/dL, MA is <0.9* LLN/>1.1* ULN; Albumin NR=3.5 - 5.3 g/dL, MA is <0.9* LLN, or if BL<LLN then use <0.75 BL
Long-term Period: Change From Baseline in Bilirubin, Blood Urea Nitrogen (BUN), Creatinine, Calcium (Ca), Phosphorus (P), Serum Glucose (Glu), and Uric Acid Over Time [ Time Frame: BL, Day 365, Day 729 ] [ Designated as safety issue: Yes ]
Bilirubin NR=0.2-1.2 mg/dL, MA: >2* ULN, or if BL>ULN then use >4* BL. BUN NR=4.0-24.0 mg/dL, MA: >2*BL. Creatinine NR=0.4-1.2 mg/dL, MA: >1.5*BL. Ca NR=8.8-10.2 mg/dL, MA: <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. P NR=2.8-4.0 mg/dL, MA: <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. Glu MA: <65 mg/dL/ >220 mg/dL. Uric acid MA: >1.5*ULN, or if BL>ULN then use >2*BL.
LT; Change From Baseline in Sodium (Na), Potassium (K), Chloride (Cl) Over Time [ Time Frame: BL, Day 365, Day 729 ] [ Designated as safety issue: Yes ]
Na NR=132 - 147 mEq/L, MA is 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. K NR=3.3 - 5.5 mEq/L, MA is <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 NR=94 - 111 mEq/L, MA is <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
Long-term Period: Mean Sitting Systolic Blood Pressure (SBP) Over Time [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ] [ Designated as safety issue: Yes ]
Measurements were taken in a seated position before and after abatacept infusion.
Long-term Period: Mean Sitting Diastolic Blood Pressure (DBP) Over Time [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ] [ Designated as safety issue: Yes ]
Measurements were taken in a seated position before and after abatacept infusion.
Long-term Period: Mean Heart Rate (HR) Over Time [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ] [ Designated as safety issue: Yes ]
Long-term Period: Mean Temperature (T) Over Time [ Time Frame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Short-term Period: Number of Participants With Clinically Meaningful Improvement (CMI) in Disease Activity Score (DAS 28), Low Disease Activity (LDAS), or Remission at Day 169 [ Time Frame: BL, Day 169 ] [ Designated as safety issue: No ]
The DAS 28 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= decrease in DAS28 score of >1.2 from baseline.
Short-term Period: Mean Time-matched Baseline (Day 0) DAS 28 and DAS 28 for Post-Baseline Visits Through 6 Month Open-Label [ Time Frame: BL (Day 0), Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169 ] [ Designated as safety issue: No ]
The DAS 28 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). Time-matched baseline (Day 0) values and post-baseline values were presented for each post-baseline visit, and represent only that cohort of participants with measurements available at that post-baseline visit.
Short-term Period: Mean Time-matched Change From Baseline (Day 0) in DAS 28 Through 6 Month Open-Label [ Time Frame: BL (Day 0), Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169 ] [ Designated as safety issue: No ]
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). Time-matched mean change from BL= Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL (Day 0) value for only that cohort of participants with measurements available at that post-BL visit.
Short-term Period: Mean Change From Baseline to Day 169 in High Sensitivity C-Reactive Protein (Hs-CRP) [ Time Frame: BL, Day 169 ] [ Designated as safety issue: No ]
hs-CRP is a acute phase reactant protein that is a clinical marker for Rheumatoid Arthritis (RA). Levels of hs-CRP can be used to determine DAS28.
Short-term Period: Mean Change From Baseline to Day 169 in Rheumatoid Factor (RF) [ Time Frame: BL, Day 169 ] [ Designated as safety issue: No ]
RF is an autoantibody (antibody directed against an organism's own tissues) most relevant in rheumatoid arthritis. It is an antibody against the Fc portion of Immunoglobulin (Ig)G, which is itself an antibody. RF and IgG join to form immune complexes which contribute to the disease process.
Short-term Period: Mean Change From Baseline to Day 169 in the Health Assessment Questionnaire Disability Index (HAQ-DI) [ Time Frame: BL, Day 169 ] [ Designated as safety issue: No ]
The HAQ-DI includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The domain 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. HAQ-DI= sum of worst scores in each domain divided by the number of domains answered. HAQ-DI ranges from a minimum of 0 (no difficulty) to a maximum overall score of 3(unable to do).
Short-term Period: Number of Participants Achieving a Clinically Meaningful HAQ Response [ Time Frame: BL, Day 169 ] [ Designated as safety issue: No ]
HAQ-DI includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The domain 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. HAQ-DI= sum of worst scores in each domain divided by the number of domains answered. HAQ-DI ranges from a minimum of 0 (no difficulty) to a maximum overall score of 3(unable to do). Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
Short-term Period: Mean Baseline Short Form 36 (SF-36) Quality of Life Physical Component Summary (PCS), Mental Component Summary (MCS), and SF-36 Individual Component Scores [ Time Frame: BL ] [ Designated as safety issue: No ]
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.
Short-term Period: Mean Change From Baseline to Day 169 in SF-36 PCS, MCS, and SF-36 Individual Component Scores [ Time Frame: BL, Day 169 ] [ Designated as safety issue: No ]
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.
Short-term Period: Mean Baseline Fatigue Visual Analog Scale (VAS) [ Time Frame: BL ] [ Designated as safety issue: No ]
The VAS for Fatigue (VAS-F) consists of a 100 mm line, with 0 (No Fatigue) on 1 end and 100 (Extreme Fatigue) on the other end, which a participant marks to indicate how much fatigue he or she feels. The marked point in mm is converted into a numeric value from 0 to 100, where 0=no fatigue and 100=maximum fatigue. Increasing numbers=increasing fatigue.
Short-term Period: Mean Change From Baseline to Day 169 in Fatigue Visual Analog Scale (VAS) [ Time Frame: BL, Day 169 ] [ Designated as safety issue: No ]
The VAS for Fatigue (VAS-F) consists of a 100 mm line, with 0 (No Fatigue) on 1 end and 100 (Extreme Fatigue) on the other end, which a participant marks to indicate how much fatigue he or she feels. The marked point in mm is converted into a numeric value from 0 to 100, where 0=no fatigue and 100=maximum fatigue. Increasing numbers=increasing fatigue.
Long-term Period: Number of Participants With Clinically Meaningful Improvement in DAS 28, Low Disease Activity, or Remission Over Time [ Time Frame: BL, Days 365, 449, 533, 617, 729, 813 ] [ Designated as safety issue: No ]
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= decrease in DAS28 score of >1.2 from baseline.
Long-term Period: Mean Time-matched Baseline (Day 0) DAS 28 and DAS 28 for Post-Baseline Visits Over the Long Term [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ] [ Designated as safety issue: No ]
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). Time-matched baseline (Day 0)values and post-baseline values were presented for each post-baseline visit, and represent only that cohort of participants with measurements available at that post-baseline visit.
Long-term Period: Mean Time-matched Change From Baseline (Day 0) in DAS 28 Over The Long Term [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ] [ Designated as safety issue: No ]
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). Time-matched mean change from BL= Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL(Day 0)value for only that cohort of participants with measurements available at that post-BL visit.
Long-term Period: Mean Time-matched Baseline (Day 0) Number of Tender Joints and Number of Tender Joints for Post-Baseline Visits Over the Long Term [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ] [ Designated as safety issue: No ]
The mean number of tender joints was evaluated based on the number of tender joints in a standard 68 joint count. Time-matched baseline (Day 0) values and post-baseline values were presented for each post-baseline visit, and represent only that cohort of participants with measurements available at that post-baseline visit.
Long-term Period: Mean Time-matched Change From Baseline (Day 0) in Number of Tender Joints Over the Long Term [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ] [ Designated as safety issue: No ]
The mean number of tender joints was evaluated based on the number of tender joints in a standard 68 joint count. Time-matched mean change from baseline = Post-baseline value - time-matched baseline value, where the time-matched baseline value represents the mean baseline (Day 0) value for only that cohort of participants with measurements available at that post-baseline visit.
Long-term Period: Mean Time-matched Baseline (Day 0) Number of Swollen Joints And Post-Baseline Number of Swollen Joints Over the Long Term [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ] [ Designated as safety issue: No ]
The mean number of swollen joints was evaluated based on the number of swollen joints in a standard 66 joint count. Time-matched baseline (Day 0) values and post-baseline values were presented for each post-baseline visit, and represent only that cohort of participants with measurements available at that post-baseline visit.
Long-term Period: Mean Time-Matched Change From Baseline (Day 0) in Number of Swollen Joints Over the Long Term [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ] [ Designated as safety issue: No ]
The mean number of swollen joints was evaluated based on the number of swollen joints in a standard 66 joint count. Time-matched mean change from baseline = Post-baseline value - time-matched baseline value, where the time-matched baseline value represents the mean baseline (Day 0) value for only that cohort of participants with measurements available at that post-baseline visit.
Long-term Period: Mean Time-matched Baseline (Day 0) Hs-CRP Levels and Hs-CRP Levels for Post-Baseline Over the Long Term [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ] [ Designated as safety issue: No ]
hs-CRP is a acute phase reactant protein that is a clinical marker for Rheumatoid Arthritis (RA). Levels of hs-CRP can be used to determine DAS28. Time-matched baseline (Day 0) values and post-baseline values were presented for each post-baseline visit, and represent only that cohort of participants with measurements available at that post-baseline visit.
Long-term Period: Mean Time-matched Change From Baseline (Day 0) in Hs-CRP Level Over the Long Term [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ] [ Designated as safety issue: No ]
hs-CRP is a acute phase reactant protein that is a clinical marker for Rheumatoid Arthritis (RA). Levels of hs-CRP can be used to determine DAS28. Time-matched mean change from baseline = Post-baseline value - time-matched baseline value, where the time-matched baseline value represents the mean baseline (Day 0) value for only that cohort of participants with measurements available at that post-baseline visit.
Long-term Period: Mean Time-matched Baseline (Day 0) Visual Analog Scale (VAS) and VAS for Post-Baseline Visits Over the Long Term [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ] [ Designated as safety issue: No ]
The VAS for Fatigue (VAS-F) consists of a 100 mm line, with 0 (No Fatigue) on 1 end and 100 (Extreme Fatigue) on the other end, which a participant marks to indicate how much fatigue he or she feels. The marked point in mm is converted into a numeric value from 0 to 100, where 0=no fatigue and 100=maximum fatigue. Increasing numbers=increasing fatigue. Time-matched baseline (Day 0) values and post-baseline values were presented for each post-baseline visit, and represent only that cohort of participants with measurements available at that post-baseline visit.
Long-term Period: Mean Time-matched Change From Baseline (Day 0) in VAS Over the Long Term [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ] [ Designated as safety issue: No ]
The VAS for Fatigue (VAS-F) consists of a 100 mm line, with 0 (No Fatigue) on 1 end and 100 (Extreme Fatigue) on the other end, which a participant marks to indicate how much fatigue he or she feels. The marked point in mm is converted into a numeric value from 0 to 100, where 0=no fatigue and 100=maximum fatigue. Increasing numbers=increasing fatigue. Time-matched mean change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL (Day 0) value for only that cohort of participants with data available at that post-BL visit.
Long-term Period: Mean Time-matched Baseline (Day 0) HAQ-DI and HAQ-DI Component Scores For Participant Cohorts at Each Corresponding Post-baseline Visit Over the Long Term [ Time Frame: BL (Day 0) ] [ Designated as safety issue: No ]
HAQ-DI includes 20 questions to assess physical functions in 8 domains:dressing, arising,eating,walking, hygiene, reach, grip and common activities. Domain 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. HAQ-DI= sum of worst scores in each domain divided by number of domains answered. HAQ-DI minimum=0 (no difficulty), max overall score=3(unable to do). Time-matched BL(Day 0)values presented for each post-BL visit represent only that cohort of participants with measurements available at that post-BL visit.
Long-term Period: Mean HAQ-DI and HAQ-DI Component Scores For Participant Cohorts at Post-baseline Visits Over the Long Term [ Time Frame: Days 365, 449, 533, 617, 729, 813 ] [ Designated as safety issue: No ]
HAQ-DI includes 20 questions to assess physical functions in 8 domains:dressing, arising, eating, walking, hygiene, reach, grip and common activities. Domain 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. HAQ-DI= sum of worst scores in each domain divided by number of domains answered. HAQ-DI minimum=0(no difficulty), max overall score=3(unable to do). Post-BL values presented for each visit represent only that cohort of participants with measurements available at that post-BL visit.
Long-term Period: Mean Time-matched Change From Baseline (Day 0) in HAQ-DI and HAQ-DI Components For Participant Cohorts at Each Corresponding Post-baseline Visit Over the Long Term [ Time Frame: BL (Day 0), Days 365, 449, 533, 617, 729, 813 ] [ Designated as safety issue: No ]
HAQ-DI includes 20 questions assessing physical functions in 8 domains:dressing,arising,eating,walking,hygiene,reach,grip and common activities.Domain questions evaluated on 4-point scale: 0=without any difficulty,1=with some difficulty,2=with much difficulty,and 3=unable to do. HAQ-DI=sum of worst scores in each domain ÷ number of domains answered. HAQ-DI minimum=0 (no difficulty), max overall score=3(unable to do). Time-matched mean change from BL= Post-BL value - time-matched BL value. Time-matched BL value=mean BL (Day 0)value for only that cohort with data available at that post-BL visit.
Long-term Period: Number of Participants Achieving Clinically Meaningful HAQ Response Over Time [ Time Frame: BL, Days 365, 449, 533, 617, 729, 813 ] [ Designated as safety issue: No ]
HAQ-DI includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The domain 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. HAQ-DI= sum of worst scores in each domain divided by the number of domains answered. HAQ-DI ranges from a minimum of 0 (no difficulty) to a maximum overall score of 3(unable to do). Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
Long-term Period: Mean Time-matched Baseline (Day 0) SF-36 PCS, MCS, and SF-36 Individual Component Scores For Participant Cohorts at Each Corresponding Post-baseline Visit Over the Long Term [ Time Frame: BL (Day 0) ] [ Designated as safety issue: No ]
SF-36 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 and 100=best score. Time-matched BL (Day 0) values presented for each post-BL visit represent only that cohort of participants with measurements available at that post-BL visit
Long-term Period: Mean SF-36 PCS, MCS, and SF-36 Individual Component Scores For Participant Cohorts at Each Post-baseline Visits Over the Long Term [ Time Frame: Days 365 and 729 ] [ Designated as safety issue: No ]
SF-36 measures health-related quality of life and 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 and 100=best score. Post-BL values presented for each post-BL visit represent only that cohort of participants with measurements available at that post-BL visit.
Long-term Period: Mean Time-matched Change From Baseline (Day 0) in SF-36 PCS, MCS, and SF-36 Individual Component Scores For Participant Cohorts at Each Corresponding Post-baseline Visit Over the Long Term [ Time Frame: BL (Day 0), Days 365, 729 ] [ Designated as safety issue: No ]
SF-36 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 and 100=best score. Time-matched mean change from BL= Post-BL value - time-matched BL value. Time-matched BL value=mean BL (Day 0)value for only that cohort with data available at that post-baseline visit.
LT; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by ELISA [ Time Frame: Days 1-813 ] [ 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.

Enrollment:	1286
Study Start Date:	April 2005
Study Completion Date:	August 2009
Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Open-label Abatacept (ABA)-Previous User In participants who have had an inadequate efficacy response or intolerance on previous TNF-antagonist therapy (off therapy for at least 2 months), open-label abatacept was administered on Days 1, 15, and 29 and then once a month thereafter on a background of non-biologic Disease Modifying Anti-Rheumatic Drug (DMARD)s. Participants weighing < 60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram of open-label abatacept by intravenous (IV) infusion.	Drug: Abatacept IV solution, IV infusion, between 500mg and 1gram based on body weight, monthly, 6 months. Other Name: Orencia Drug: Non-biologic Disease Modifying Anti-Rheumatic Drug (DMARD) During the study, subjects continued to receive 1 or more background non-biologic DMARDs (e.g. methotrexate, leflunomide) at the dose level(s) and regimen(s) administered at the time of abatacept treatment onset (Day 1).
Experimental: Open-label ABA-Current User In participants currently using Tumor Necrosis Factor (TNF)-agonists, open-label abatacept was administered on Days 1, 15, and 29 and then once a month thereafter on a background of non-biologic Disease Modifying Anti-Rheumatic Drug (DMARD)s. Participants weighing < 60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing > 100 kg received 1 gram of open-label abatacept by intravenous (IV) infusion.	Drug: Abatacept IV solution, IV infusion, between 500mg and 1gram based on body weight, monthly, 6 months. Other Name: Orencia Drug: Non-biologic Disease Modifying Anti-Rheumatic Drug (DMARD) During the study, subjects continued to receive 1 or more background non-biologic DMARDs (e.g. methotrexate, leflunomide) at the dose level(s) and regimen(s) administered at the time of abatacept treatment onset (Day 1). Drug: Anti-Tumor Necrosing Factor (TNF) Therapy Any of the anti-TNF therapies (Infliximab, Adalimumab, Etanercept, etc.)administered at the approved label dose for at least 3 months
Experimental: Long-term ABA Participants continued to receive the same 10 mg/kg weight-tiered dose of abatacept that they received in the initial short-term period.	Drug: Abatacept IV solution, IV infusion, between 500mg and 1gram based on body weight, monthly, 6 months. Other Name: Orencia Drug: Non-biologic Disease Modifying Anti-Rheumatic Drug (DMARD) During the study, subjects continued to receive 1 or more background non-biologic DMARDs (e.g. methotrexate, leflunomide) at the dose level(s) and regimen(s) administered at the time of abatacept treatment onset (Day 1).

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00124982 History of Changes
Other Study ID Numbers:	IM101-064
Study First Received:	June 30, 2005
Results First Received:	February 18, 2011
Last Updated:	November 4, 2011
Health Authority:	United States: Food and Drug Administration