Phase III Study of BMS-188667 (CTLA4Ig) in Patients With Rheumatoid Arthritis Who Are Currently Failing Anti-TNF Therapy or Who Have Failed Anti-TNF Therapy in the Past.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00048581
First received: November 2, 2002
Last updated: November 14, 2011
Last verified: November 2011
  Purpose

The purpose of this clinical research study is to determine whether abatacept treatment on a background of Disease Modifying Antirheumatic Drugs (DMARDs) will relieve the symptoms of rheumatoid arthritis (RA) in participants who are currently receiving anti-tumor necrosis factor (TNF) therapy for at least 3 months and are not responding or have taken anti-TNF therapy in the last 3 months and did not respond. The safety of treatment with abatacept will also be evaluated. This study also has a 4.5-year long-term extension beginning 6 months after the start of the study.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Abatacept
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of BMS-188667 in Subjects With Active Rheumatoid Arthritis on Background Disease Modifying Anti-Rheumatic Drugs (DMARDS) Who Have Failed Anti-Tumor Necrosis Factor (TNF) Therapy

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Double-blind Period (DB); Number of Participants With American College of Rheumatology (ACR) 20 Response at Day 169 [ Time Frame: Day 169 ] [ Designated as safety issue: No ]
    ACR 20 response requires a participant to have a 20% reduction in the number of swollen and tender joints, and a reduction of 20% in three of the following five parameters: physician global assessment of disease, participant global assessment of disease, participant assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in Health Assessment Questionnaire (HAQ) score. A participant achieved a sustained ACR 20 response if the participant had ACR 20 observed for at least 2 consecutive study visits.

  • DB; Number of Participants Achieving Clinically Meaningful Improvement in Health Assessment Questionnaire (HAQ) [ Time Frame: Day 169 ] [ Designated as safety issue: No ]
    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.

  • Open-Label Period (OL); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation [ Time Frame: From first day of OL to 5.5 years ] [ 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

  • OL; Number of Participants AEs of Special Interest [ Time Frame: From first day of OL to 5.5 years ] [ 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: From first day of OL to 5.5 years ] [ 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.

  • OL; Number of Participants With Blood Chemistry Laboratories Meeting Marked Abnormality Criteria [ Time Frame: From first day of OL to 5.5 years ] [ 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; Mean Time-matched Baseline Immunoglobulin (Ig) Levels Over the OL [ Time Frame: Baseline and Days 169, 365, 729, and 1093 ] [ Designated as safety issue: Yes ]
    Serum samples collected from participants were used to determine serum levels of IgA, IgM, and IgG. Time-matched baseline values were presented by visit and represented the mean baseline value for only that cohort of participants with serum samples available at that visit.

  • OL; Mean Time-matched Change From Baseline in Immunoglobulin (Ig) Levels Over the OL [ Time Frame: BL, Days 169, 365, 729, and 1093 ] [ Designated as safety issue: Yes ]
    Serum samples collected from participants were used to determine serum levels of IgA, IgM, and IgG. Time-matched mean change from baseline = Post-baseline value - time-matched baseline value, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with serum samples available at that visit.


Secondary Outcome Measures:
  • DB; Number of Participants With ACR 20, ACR 50, and ACR 70 Responses Over Time [ Time Frame: Days 15, 29, 57, 85, 113, 141, and 169 ] [ Designated as safety issue: No ]
    ACR 20/50/70 response requires a participant to have a 20/50/70% reduction in the number of swollen and tender joints, and a reduction of 20/50/70% in three of the following five parameters: physician global assessment of disease, participant global assessment of disease, participant assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in Health Assessment Questionnaire (HAQ) score. A participant achieved a sustained ACR 20/50/70 response if the participant had ACR 20/50/70 observed for at least 2 consecutive study visits.

  • DB; Mean Time-matched Baseline Tender Joint Counts (TJCs) and Post-Baseline TJCs Over Time: ACR Core Component [ Time Frame: BL ] [ Designated as safety issue: No ]
    The mean TJC core component of the ACR scoring system was evaluated based on the number of tender joints in a standard 68 joint count, where an increasing number of tender joints indicates increasing level of severity. Time-matched baseline TJC values for each post-baseline TJC in the DB were presented for each visit and represent the mean baseline TJC value for only that cohort of participants with TJCs available at that visit.

  • DB; Mean Time-Matched Percentage of Change From Baseline in TJC Over Time: ACR Core Component [ Time Frame: BL, Days 15, 29, 57, 85, 113, 141, and 169 ] [ Designated as safety issue: No ]
    The mean TJC core component of the ACR scoring system was evaluated based on the number of tender joints in a standard 68 joint count, where an increasing number of tender joints indicates increasing level of severity. Mean Time-matched percentage of change from baseline = (time-matched baseline value - Post-baseline value)/time-matched baseline value x 100, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with TJCs available at that visit.

  • DB; Mean Time-matched Baseline Swollen Joint Count (SJC) and Post-Baseline SJCs Over Time: ACR Core Component [ Time Frame: Days 15, 29, 57, 85, 113, 141, and 169 ] [ Designated as safety issue: No ]
    The mean SJC core component of the ACR scoring system was evaluated based on the number of swollen joints in a standard 66 joint count, where an increasing number of swollen joints indicates increasing level of severity. Time-matched baseline SJC values for each post-baseline SJC in the DB were presented for each visit and represent the mean baseline SJC value for only that cohort of participants with SJCs available at that visit.

  • DB; Mean Time-Matched Percentage of Change From Baseline in SJC Over Time: ACR Core Component [ Time Frame: Days 15, 29, 57, 85, 113, 141, and 169 ] [ Designated as safety issue: No ]
    The mean SJC core component of the ACR scoring system was evaluated based on the number of swollen joints in a standard 66 joint count, where an increasing number of swollen joints indicate increasing level of severity. Mean Time-matched percentage of change from baseline = (time-matched baseline value - Post-baseline value)/time-matched baseline value x 100, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with TJCs available at that visit.

  • DB; Mean Time-matched Baseline Participant Pain Assessment Over Time: ACR Core Component [ Time Frame: BL ] [ Designated as safety issue: No ]
    The participant self-reported pain assessment is a core component of the ACR scoring system where increasing score indicates increasing level of severity as indicated on a 100 mm Visual Analog Scale (VAS) with 0 mm representing no pain and 100 mm representing the most pain possible. For each post-baseline visit in the DB, time-matched baseline Participant Pain Assessment values were presented and represent the mean baseline value for only that cohort of participants with assessments available at that visit.

  • DB; Mean Time-Matched Percentage of Change From Baseline in Participant Pain Assessment Over Time: ACR Core Component [ Time Frame: BL, Days 15, 29, 57, 85, 113, 141, and 169 ] [ Designated as safety issue: No ]
    Participant self-reported pain assessment is a core component of the ACR scoring system where increasing score indicates increasing level of severity as indicated on a 100 mm Visual Analog Scale (VAS) with 0 mm representing no pain and 100 mm representing the most pain possible. Mean Time-matched percentage of change from baseline = (time-matched baseline value - Post-baseline value)/time-matched baseline value x 100, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with assessments available at that visit.

  • DB; Mean Time-matched Baseline HAQ-DI Over Time: ACR Core Component [ Time Frame: BL ] [ Designated as safety issue: No ]
    HAQ-DI is a self-administered questionnaire composed of 20 questions assessing physical function in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. 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. The HAQ-DI is the weighted sum of the scale scores, with higher scores indicating poorer function. For each post-BL visit, time-matched BL HAQ-DI values were presented and represent the mean BL value for only that cohort of participants with data available at that visit.

  • DB; Mean Time-Matched Percentage of Change From Baseline in HAQ-DI Over Time: ACR Core Component [ Time Frame: BL, Days 15, 29, 57, 85, 113, 141, and 169 ] [ Designated as safety issue: No ]
    A self-administered questionnaire with 20 questions assessing physical function in 8 domains:dressing,arising,eating,walking,hygiene,reach,grip and common activities.Questions 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=weighted sum of scale scores, with higher scores indicating poorer function. Mean time-matched % change from BL=(time-matched BL value - Post-BL value)/time-matched BL value x100, where time-matched BL value=the mean BL value for only that cohort of participants with data available at that visit.

  • DB; Mean Time-matched Baseline Participant Global Assessment Over Time: ACR Core Component [ Time Frame: BL ] [ Designated as safety issue: No ]
    Participant self-reported global RA assessment core component of the ACR scoring system where increasing score indicates increasing level of severity as indicated on a 100 mm Visual Analog Scale (VAS) with 0 mm representing no pain and 100 mm representing the most pain possible. For each post-baseline visit in the DB, time-matched baseline Participant Global Assessment values were presented and represent the mean baseline value for only that cohort of participants with assessments available at that visit.

  • DB; Mean Time-Matched Percentage of Change From Baseline in Participant Global Assessment Over Time: ACR Core Component [ Time Frame: BL, Days 15, 29, 57, 85, 113, 141, and 169 ] [ Designated as safety issue: No ]
    Participant self-reported global RA assessment core component of the ACR scoring system where increasing score indicates increasing level of severity as indicated on a 100mm Visual Analog Scale (VAS) with 0mm representing no pain and 100mm representing the most pain possible. Mean Time-matched percentage of change from baseline = (time-matched baseline value - Post-baseline value)/time-matched baseline value x 100, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with assessments available at that visit.

  • DB; Mean Time-matched Baseline Physician Global Assessment Over Time: ACR Core Component [ Time Frame: BL ] [ Designated as safety issue: No ]
    Physician global rheumatoid arthritis (RA) assessment core component of the ACR scoring system where increasing score indicates increasing level of severity as indicated on a 100mm Visual Analog Scale (VAS) with 0mm representing no pain and 100mm representing the most pain possible. For each post-baseline visit in the DB, time-matched baseline Physician Global Assessment values were presented and represent the mean baseline value for only that cohort of participants with assessments available at that visit.

  • DB; Mean Time-Matched Percentage of Change From Baseline in Physician Global Assessment Over Time: ACR Core Component [ Time Frame: BL, Days 15, 29, 57, 85, 113, 141, and 169 ] [ Designated as safety issue: No ]
    Physician global rheumatoid arthritis (RA) assessment core component of the ACR scoring system where increasing score indicates increasing level of severity as indicated on a 100mm Visual Analog Scale (VAS) with 0mm representing no pain and 100mm representing the most pain possible. Mean Time-matched percentage of change from baseline = (time-matched baseline value - Post-baseline value)/time-matched baseline value x 100, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with assessments available at that visit.

  • DB; Mean Time-matched Baseline C-Reactive Protein (CRP) Levels Over Time: ACR Core Component [ Time Frame: BL ] [ Designated as safety issue: No ]
    CRP is an acute phase reactant protein that is a clinical marker for Rheumatoid Arthritis (RA) and a core component of the ACR scoring system. CRP was evaluated from serum samples. Increasing levels of CRP indicate increasing level of disease. For each post-baseline visit in the DB, time-matched baseline CRP values were presented and represent the mean baseline value for only that cohort of participants with assessments available at that visit.

  • DB; Mean Time-Matched Percentage of Change From Baseline in CRP Levels Over Time: ACR Core Component [ Time Frame: Days 15, 29, 57, 85, 113, 141, and 169 ] [ Designated as safety issue: No ]
    CRP is an acute phase reactant protein that is a clinical marker for Rheumatoid Arthritis (RA) and a core component of the ACR scoring system. CRP was evaluated from serum samples. Increasing levels indicate increasing level of disease. Mean Time-matched percentage of change from baseline = (time-matched baseline value - Post-baseline value)/time-matched baseline value x 100, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with data available at that visit.

  • DB; Mean Baseline Levels of Disease Biomarkers (Interleukin-6 (IL-6), Soluble IL-2 Receptor [sIL-2R], and Tumor Necrosing Factor [TNF]-Alpha) in Participants With Measurements at Day 169 [ Time Frame: BL ] [ Designated as safety issue: No ]
    Potential biomarkers of disease (IL-6, SIL-2R, and TNF-Alpha) were determined from serum samples for all participants. The mean baseline value presented represents a time-matched Day 169 baseline value for only that cohort of participants with assessments available at that visit.

  • DB; Mean Change From Baseline to Day 169 in Levels of Disease Biomarkers (IL-6, sIL-2R, and TNF-alpha) in Participants With Measurements at Day 169 [ Time Frame: BL, Day 169 ] [ Designated as safety issue: No ]
    The mean change from baseline in levels of potential biomarkers of disease (IL-6, SIL-2R, and TNF-Alpha) were determined from serum samples for all participants. Change from Baseline = Post-baseline value - time-matched baseline value, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with data available at Day 169.

  • DB; Mean Baseline Levels of Disease Biomarkers (E-Selectin, Soluble Inter-Cellular Adhesion Molecule 1 [sICAM-1], and Matrix Metalloproteinase-3 [MMP-3]) in Participants With Measurements at Day 169 [ Time Frame: BL ] [ Designated as safety issue: No ]
    Potential biomarkers of disease (E-selectin, sICAM-1, and MMP-3) were determined from serum samples for all participants. The mean baseline value presented represents a time-matched Day 169 baseline value for only that cohort of participants with assessments available at that visit.

  • DB; Mean Change From Baseline to Day 169 in Levels of Disease Biomarkers (E-Selectin, sICAM-1, and MMP-3) in Participants With Measurements at Day 169 [ Time Frame: BL, Day 169 ] [ Designated as safety issue: No ]
    Potential biomarkers of disease (E-selectin, sICAM-1, and MMP-3) were determined from serum samples for all participants. Change from Baseline = Post-baseline value - time-matched baseline value, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with data available at Day 169.

  • DB; Mean Change From Baseline to Day 169 in Rheumatoid Factor (RF) Status [ Time Frame: BL, Day 169 ] [ Designated as safety issue: No ]
    Rheumatoid factor (RF or RhF) 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. A positive value for RF was >20 IU/mL; a negative value for RF was ≤ 20 IU/mL.

  • DB; Mean Baseline Short Form 36 (SF-36) Quality of Life Physical Component Summary (PCS), Mental Component Summary (MCS), and SF-36 Individual Component Scores For Participants With Measurements at Day 85 [ Time Frame: BL ] [ Designated as safety issue: No ]
    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: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. 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. Mean BL value presented represents a time-matched Day 85 BL value for only that cohort of participants with data available at that visit.

  • DB; Adjusted Mean Change From Baseline to Day 85 in Short SF-36 PCS, MCS, and SF-36 Individual Component Scores [ Time Frame: BL, Day 85 ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0=worst score (or quality of life) and 100=best score. Change from Baseline= Post-baseline value - time-matched baseline value, where time-matched BL value = the mean BL value for only that cohort of participants with data available at Day 85.

  • DB; Mean Baseline SF-36 PCS, MCS, and SF-36 Individual Component Scores For Participants With Measurements at Day 169 [ Time Frame: BL ] [ Designated as safety issue: No ]
    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: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. 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. Mean BL value presented represents a time-matched Day 169 BL value for only that cohort of participants with data available at that visit.

  • DB; Adjusted Mean Change From Baseline to Day 169 in SF-36 PCS, MCS, and SF-36 Individual Component Scores For Participants With Measurements at Day 169 [ Time Frame: BL, Day 169 ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0=worst score (or quality of life) and 100=best score. Change from Baseline= Post-baseline value - time-matched baseline value, where time-matched BL value = the mean BL value for only that cohort of participants with data available at Day 169.

  • DB; Mean Baseline HAQ-DI and HAQ Component Scores in Participants With Assessments at Day 169 [ Time Frame: BL ] [ Designated as safety issue: No ]
    The HAQ DI is a self-administered questionnaire composed of 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. 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 is a weighted sum of the scale scores, with a higher score indicating poorer function. The mean baseline value presented represents a time-matched Day 169 baseline value for only that cohort of participants with assessments available at that visit.

  • DB; Adjusted Mean Change From Baseline to Day 169 in HAQ-DI and HAQ Component Scores in Participants With Assessments at Day 169 [ Time Frame: BL, Day 169 ] [ Designated as safety issue: No ]
    HAQ DI is a self-administered questionnaire composed of 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. Questions 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=weighted sum of the scale scores. Higher score indicates poorer function.Change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at Day 169.

  • DB; Mean Disease Activity Score (DAS)28 (C-Reactive Protein [CRP]) and Mean Disease Activity Score (Erythrocyte Sedimentation Rate [ESR]) at Day 169 [ Time Frame: BL, 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 levels, 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. The mean BL value presented represents a time-matched Day 169 BL value for only that cohort of participants with assessments available at that visit.

  • DB; Adjusted Mean Change From Baseline to Day 169 in DAS28 (CRP) and DAS28 (ESR) [ Time Frame: BL, 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). Change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at Day 169.

  • DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation [ Time Frame: From BL up to database lock for DB period (6/2/2004) ] [ 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

  • DB; Number of Participants AEs of Special Interest [ Time Frame: From BL up to database lock for DB period (6/2/2004) ] [ 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 (MA) Criteria [ Time Frame: From BL up to database lock for DB period (6/2/2004) ] [ 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.

  • DB; Number of Participants With Blood Chemistry Laboratories Meeting MA Criteria [ Time Frame: From BL up to database lock for DB period (6/2/2004) ] [ 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

  • 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: From BL to Day 169 ] [ Designated as safety issue: No ]
    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.

  • OL; Number of Participants With ACR 20, ACR 50, and ACR 70 Responses Over Time For Participants Treated in the OL [ Time Frame: Days 15, 29, 57, 85, 113, 141, 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1261, 1457, 1625, and 1821 ] [ Designated as safety issue: No ]
    ACR 20/50/70 response requires a participant to have a 20/50/70% reduction in the number of swollen and tender joints, and a reduction of 20/50/70% in three of the following five parameters: physician global assessment of disease, participant global assessment of disease, participant assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in Health Assessment Questionnaire (HAQ) score. A participant achieved a sustained ACR 20/50/70 response if the participant had ACR 20/50/70 observed for at least 2 consecutive study visits.

  • OL; Number of Participants With Low Disease Activity (LDAS) or Remission For Participants Treated in the OL [ Time Frame: Days 15, 29, 57, 85, 113, 141, 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1261, 1457, 1625, and 1821 ] [ 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.

  • OL; Mean Time-matched Baseline DAS28 (CRP) Over Time For Participants Treated in the OL [ Time Frame: BL ] [ 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 levels, 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 values were presented by visit and represented the mean baseline value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Change From Baseline in DAS28 (CRP) Over Time For Participants Treated in the OL [ Time Frame: BL, Days 15, 29, 57, 85, 113, 141, 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1261, 1457, 1625, and 1821 ] [ Designated as safety issue: No ]
    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 baseline = Post-baseline value - time-matched baseline value, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Baseline DAS28 (ESR) Over Time For Participants Treated in the OL [ Time Frame: BL ] [ 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 levels, 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 values were presented by visit and represented the mean baseline value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Change From Baseline in DAS28 (ESR) Over Time For Participants Treated in the OL [ Time Frame: BL, Days 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1261, 1457, 1625, and 1821 ] [ Designated as safety issue: No ]
    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 baseline = Post-baseline value - time-matched baseline value, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with data available at that visit.

  • OL; Number of Participants Achieving HAQ Response Over Time In Participants Treated in the OL [ Time Frame: Days 15, 29, 57, 85, 113, 141, 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1261, 1457, 1625, and 1821 ] [ Designated as safety issue: No ]
    The HAQ disability index (HAQ DI) is a self-administered questionnaire composed of 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. The HAQ disease index is a weighted sum of the scale scores, with a higher score indicating poorer function. Clinically meaningful HAQ response was defined as an improvement of at least 0.3 units from baseline in HAQ DI.

  • OL; Mean Time-matched Baseline HAQ-DI and HAQ Component Scores Over Time For Participants Treated in the OL [ Time Frame: BL ] [ Designated as safety issue: No ]
    The HAQ DI is a self-administered questionnaire composed of 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. 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 is a weighted sum of the scale scores, with a higher score indicating poorer function. Time-matched baseline values were presented by visit and represented the mean baseline value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Change From Baseline in HAQ-DI and HAQ Component Scores For Participants Treated in the OL [ Time Frame: BL, Days 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1261, 1457, 1625, and 1821 ] [ Designated as safety issue: No ]
    HAQ-DI is a self-administered questionnaire composed of 20 questions to assess physical functions in 8 domains:dressing, arising, eating, walking, hygiene, reach, grip and common activities. Questions 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=weighted sum of the scale scores. Higher score indicates poorer function.Change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at that visit

  • OL; Mean Time-matched Baseline Levels of Rheumatoid Factor (RF) Over Time For Participants Treated in the OL [ Time Frame: BL ] [ Designated as safety issue: No ]
    RF is an autoantibody 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. Time-matched baseline levels of RF were presented by visit and represented the mean baseline value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Change From Baseline in Levels of RF Over Time For Participants Treated in the OL [ Time Frame: BL, Days 169, 365, 729, 1093, 1261, 1457, and 1821 ] [ Designated as safety issue: No ]
    RF is an autoantibody 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. Change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Baseline Levels of C-Reactive Protein (CRP) Over Time For Participants Treated in the OL [ Time Frame: BL ] [ Designated as safety issue: No ]
    CRP is an acute phase reactant protein that is a clinical marker for Rheumatoid Arthritis (RA). Time-matched baseline levels of CRP were presented by visit and represented the mean baseline value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Change From Baseline in Levels of CRP Over Time For Participants Treated in the OL [ Time Frame: BL, Days 169, 365, 729, 1093, 1261, 1457, and 1821 ] [ Designated as safety issue: No ]
    CRP is an acute phase reactant protein that is a clinical marker for RA. Change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Baseline Erythrocyte Sedimentation Rate (ESR) Over Time For Participants Treated in the OL [ Time Frame: BL ] [ Designated as safety issue: No ]
    ESR, also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour. It is a common hematology test that is a non-specific measure of inflammation. Time-matched baseline levels of ESR were presented by visit and represented the mean baseline value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Change From Baseline in ESR Over Time For Participants Treated in the OL [ Time Frame: BL, Days 169, 365, 729, 1093, 1261, 1457, and 1821 ] [ Designated as safety issue: No ]
    ESR, also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour. It is a common hematology test that is a non-specific measure of inflammation. Change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Baseline Levels of Soluble Interleukin 2 Receptor (sIL-2R) Over Time For Participants Treated in the OL [ Time Frame: BL ] [ Designated as safety issue: No ]
    IL-2 is a proinflammatory cytokine, and the soluble form of its receptor (IL-2R) is a marker for inflammation. Time-matched baseline levels of IL-2R were presented by visit and represented the mean baseline value for only that cohort of participants with data available at that visit

  • OL; Mean Time-matched Change From Baseline in Levels of sIL-2R Over Time For Participants Treated in the OL [ Time Frame: BL, Days 169, 365, 729, 1093, 1261, 1457, and 1821 ] [ Designated as safety issue: No ]
    IL-2 is a proinflammatory cytokine, and the soluble form of its receptor (IL-2R) is a marker for inflammation. Change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Baseline SF-36 PCS and MCS Over Time For Participants Treated in OL [ Time Frame: BL ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores:PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. 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. Time-matched baseline values were presented by visit and represented the mean baseline value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Change From Baseline in SF-36 PCS and MCS Over Time For Participants Treated in OL [ Time Frame: BL, Days 169, 365, 729, 1093, 1457, and 1821 ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0=worst score (or quality of life) and 100=best score. Change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Baseline Physical Function Score Over Time For Participants Treated in the OL [ Time Frame: BL ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores:PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. 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. Time-matched baseline values were presented by visit and represented the mean baseline value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Change From Baseline in Physical Function Score Over Time For Participants Treated in the OL [ Time Frame: BL, Days 169, 365, 729, 1093, 1457, and 1821 ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0=worst score (or quality of life) and 100=best score. Change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Baseline Role-Physical Score Over Time For Participants Treated in the OL [ Time Frame: BL ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores:PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. 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. Time-matched baseline values were presented by visit and represented the mean baseline value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Change From Baseline in Role-Physical Score Over Time For Participants Treated in the OL [ Time Frame: BL, Days 169, 365, 729, 1093, 1457, and 1821 ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0=worst score (or quality of life) and 100=best score. Change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Baseline Bodily Pain Score Over Time For Participants Treated in the OL [ Time Frame: BL ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores:PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. 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. Time-matched baseline values were presented by visit and represented the mean baseline value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Change From Baseline in Bodily Pain Score Over Time For Participants Treated in the OL [ Time Frame: BL, Days 169, 365, 729, 1093, 1457, and 1821 ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0=worst score (or quality of life) and 100=best score. Change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Baseline General Health Score Over Time For Participants Treated in the OL [ Time Frame: BL ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores:PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. 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. Time-matched baseline values were presented by visit and represented the mean baseline value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Change From Baseline in General Health Score Over Time For Participants Treated in the OL [ Time Frame: BL, Days 169, 365, 729, 1093, 1457, and 1821 ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0=worst score (or quality of life) and 100=best score. Change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Baseline Vitality Score Over Time For Participants Treated in the OL [ Time Frame: BL ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores:PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. 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. Time-matched baseline values were presented by visit and represented the mean baseline value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Change From Baseline in Vitality Score Over Time For Participants Treated in the OL [ Time Frame: BL, Days 169, 365, 729, 1093, 1457, and 1821 ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0=worst score (or quality of life) and 100=best score. Change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Baseline Social Functioning Score Over Time For Participants Treated in the OL [ Time Frame: BL ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores:PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. 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. Time-matched baseline values were presented by visit and represented the mean baseline value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Change From Baseline in Social Functioning Score Over Time For Participants Treated in the OL [ Time Frame: BL, Days 169, 365, 729, 1093, 1457, and 1821 ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0=worst score (or quality of life) and 100=best score. Change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Baseline Role-Emotional Score Over Time For Participants Treated in the OL [ Time Frame: BL ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores:PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. 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. Time-matched baseline values were presented by visit and represented the mean baseline value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Change From Baseline in Role-Emotional Score Over Time For Participants Treated in the OL [ Time Frame: BL, Days 169, 365, 729, 1093, 1457, and 1821 ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0=worst score (or quality of life) and 100=best score. Change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Baseline Mental Health Score Over Time For Participants Treated in the OL [ Time Frame: BL ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores:PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. 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. Time-matched baseline values were presented by visit and represented the mean baseline value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Change From Baseline in Mental Health Score Over Time For Participants Treated in the OL [ Time Frame: BL, Days 169, 365, 729, 1093, 1457, and 1821 ] [ Designated as safety issue: No ]
    SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0=worst score (or quality of life) and 100=best score. Change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Baseline Medical Outcomes Study Sleep Module (MOS-sleep) Score Over Time For Participants Treated in the OL [ Time Frame: BL ] [ Designated as safety issue: No ]
    The validated 12-it3em Medical Outcomes Study sleep questionnaire (MOS-sleep) was used to measure sleep quality. An overall Sleep Problem Index (SPI) was generated as a summary measure of different types of sleep problems (sleep disturbance, sleep quantity, sleep adequacy, etc.). The score ranges from 0 to 100 with a higher score reflecting more severe problems with sleep. The mean score of the SPI in a population with chronic problems is 29.

  • OL; Mean Time-matched Change From Baseline in MOS-Sleep Score Over Time For Participants Treated in the OL [ Time Frame: BL, Days 169, 365, 729, 1093, 1457, and 1821 ] [ Designated as safety issue: No ]
    The validated 12-it3em Medical Outcomes Study sleep questionnaire (MOS-sleep) was used to measure sleep quality. An overall Sleep Problem Index (SPI) was generated as a summary measure of different types of sleep problems (sleep disturbance, sleep quantity, sleep adequacy, etc.). The score ranges from 0 to 100 with a higher score reflecting more severe problems with sleep. Change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Baseline Fatigue Visual Analog Score (VAS) Over Time For Participants Treated in the OL [ Time Frame: BL ] [ Designated as safety issue: No ]
    Fatigue severity was assessed on the VAS 100 mm where 0= no fatigue to 100 = the worst fatigue imaginable. Time-matched baseline values were presented by visit and represented the mean baseline value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Change From Baseline in Fatigue VAS Over Time For Participants Treated in the OL [ Time Frame: BL, Days 169, 365, 729, 1093, 1457, and 1821 ] [ Designated as safety issue: No ]
    Fatigue severity was assessed on the VAS 100 mm where 0= no fatigue to 100 = the worst fatigue imaginable. Change from BL = Post-BL value - time-matched BL value, where the time-matched BL value represents the mean BL value for only that cohort of participants with data available at that visit.

  • OL; Mean Time-matched Baseline Activity Limitation Score Over Time For Participants Treated in the OL [ Time Frame: BL ] [ Designated as safety issue: No ]
    Limitations on activities of daily living in the OL period at each study visit were measured by a 2-item questionnaire that was developed to collect data on the amount of time that a participant is unable to perform their usual activities because of their rheumatoid arthritis. Time-matched baseline values were presented by visit and represented the mean baseline value for only that cohort of participants with data available at that visit. The scale ranges from 0 to 100 with increasing score indicating increasing restrictions on levels of activity.

  • OL; Mean Change From Baseline in Activity Limitation Score Over Time For Participants Treated in the OL [ Time Frame: Days 169, 365, 729, 1093, 1457, and 1821 ] [ Designated as safety issue: No ]
    Limitations on activities of daily living in the OL period at each study visit was measured by a 2-item questionnaire that was developed to collect data on the amount of time that a participant is unable to perform their usual activities because of their rheumatoid arthritis. The scale ranges from 0 to 100 with increasing score indicating increasing restrictions on levels of activity.

  • Cumulative Analysis (DB + OL); Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by Enzyme-Linked Immunosorbent Assay (ELISA) [ Time Frame: From BL (Day 1) to Day 1821 ] [ Designated as safety issue: No ]
    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: 738
Study Start Date: December 2002
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Abatacept
Short Term Portion of Study
Drug: Abatacept
Vials, intravenous (IV), ~10mg/kg abatacept, One every 2 weeks for first month then every 4 weeks thereafter, 6 months.
Other Names:
  • Orencia
  • BMS-188667
  • CTLA4Ig
Placebo Comparator: Placebo
Short Term Portion of Study
Drug: Placebo
Vials, IV, 0mg, One every 2 weeks for first month then every 4 weeks thereafter, 6 months.
Active Comparator: Abatacept (Long Term)

Long Term Portion of Study:

All participants receive Active Drug

Drug: Abatacept
Vials, IV, ~10mg/kg abatacept, every 4 weeks, 5.5 years
Other Names:
  • Orencia
  • BMS-188667
  • CTLA4Ig

  Eligibility

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

Eligibility Criteria:

  • Active rheumatoid arthritis currently failing anti-TNF therapy or have failed anti-TNF therapy in the past.

Exclusion Criteria:

  • Women who are pregnant or breast feeding
  • Current symptoms of serious medical disease
  • History of cancer in last 5 years other than non-melanoma skin cancer
  • Chronic serious infection
  • Active TB requiring treatment in last 5 years
  • Herpes zoster in last 2 months
  • Any active viral infection including Human Immunodeficiency Virus (HIV)
  • Serious side effects associated with previous anti-TNF therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00048581

  Show 42 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
  More Information

Additional Information:
Publications:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00048581     History of Changes
Other Study ID Numbers: IM101-029
Study First Received: November 2, 2002
Results First Received: April 7, 2011
Last Updated: November 14, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Abatacept
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014