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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00124982
• Other study ID #: IM101-064
• Status: Completed
• Phase: Phase 3
• First received: June 30, 2005
• Last updated: February 23, 2012
• Start date: April 2005
• Est. completion date: August 2009

Study information

• Verified date: February 2012
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1286
• Est. completion date: August 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Completed double-blind portion of the IM101064 study.

• Rheumatoid arthritis (RA) for greater than 1 year from the time of initial diagnosis

• American College of Rheumatology (ACR) functional class I, II, III

• Subjects currently or previously received an anti-TNF therapy at an approved labeled dose for at least 3 months

Exclusion Criteria:

• Subjects with active vasculitis of a major organ system (except subcutaneous rheumatoid nodules)

• History of cancer within the last 5 years (other than non-melanoma skin cell cancers cured by local resection)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Abatacept
IV solution, IV infusion, between 500mg and 1gram based on body weight, monthly, 6 months.
• 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).
• 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

Locations

Country	Name	City	State
Belgium	Local Institution	Bruxelles
Belgium	Local Institution	Leuven
Czech Republic	Local Institution	Prague 2
France	Local Institution	Boisguillaume
France	Local Institution	Bordeaux Cedex
France	Local Institution	Brest Cedex
France	Local Institution	Chambray Les Tours
France	Local Institution	Montpellier
France	Local Institution	Nice Cedex 03
France	Local Institution	Paris
France	Local Institution	Rennes Cedex 9
France	Local Institution	Strasbourg Cedex
France	Local Institution	Toulouse
Germany	Local Institution	Freiburg
Germany	Local Institution	Hamburg
Germany	Local Institution	Kiel
Germany	Local Institution	Leipzig
Germany	Local Institution	Tuebingen
Ireland	Local Institution	Cork
Italy	Local Institution	Genova
Italy	Local Institution	Milano
Italy	Local Institution	Torino
Mexico	Local Institution	Distrito Federal
Mexico	Local Institution	Guadalajara	Jalisco
Spain	Local Institution	Alicante
Spain	Local Institution	Barcelona
Spain	Local Institution	Guipuzcoa
Spain	Local Institution	Madrid
Spain	Local Institution	Santander
Spain	Local Institution	Valencia
United Kingdom	Local Institution	Cambridge	Cambridgeshire
United Kingdom	Local Institution	Leeds	North Yorkshire
United Kingdom	Local Institution	Maidstone	Kent
United Kingdom	Local Institution	Manchester	Greater Manchester
United States	Local Institution	Akron	Ohio
United States	Local Institution	Albany	New York
United States	Local Institution	Ann Arbor	Michigan
United States	Local Institution	Asheville	North Carolina
United States	Local Institution	Atlanta	Georgia
United States	Local Institution	Austin	Texas
United States	Local Institution	Aventura	Florida
United States	Local Institution	Bala Cynwyd	Pennsylvania
United States	Local Institution	Beachwood	Ohio
United States	Local Institution	Bethlehem	Pennsylvania
United States	Local Institution	Birmingham	Alabama
United States	Local Institution	Bismark	North Dakota
United States	Local Institution	Blue Ridge	Georgia
United States	Local Institution	Boston	Massachusetts
United States	Local Institution	Bowling Green	Kentucky
United States	Local Institution	Brooklyn	New York
United States	Local Institution	Burke	Virginia
United States	Local Institution	Camp Hill	Pennsylvania
United States	Local Institution	Charlotte	North Carolina
United States	Local Institution	Cherry Hill	New Jersey
United States	Local Institution	Chesapeake	Virginia
United States	Local Institution	Clearwater	Florida
United States	Local Institution	Cleveland	Ohio
United States	Local Institution	Colorado Springs	Colorado
United States	Local Institution	Columbus	Ohio
United States	Local Institution	Corpus Christi	Texas
United States	Local Institution	Dallas	Texas
United States	Local Institution	Danbury	Connecticut
United States	Local Institution	Denver	Colorado
United States	Local Institution	Des Moines	Iowa
United States	Local Institution	Dover	New Jersey
United States	Local Institution	Duncansville	Pennsylvania
United States	Local Institution	East Lansing	Michigan
United States	Local Institution	Erie	Pennsylvania
United States	Local Institution	Evansville	Indiana
United States	Local Institution	Fairfax	Virginia
United States	Local Institution	Ft. Lauderdale	Florida
United States	Local Institution	Galveston	Texas
United States	Local Institution	Glendale	Wisconsin
United States	Local Institution	Grand Rapids	Michigan
United States	Local Institution	Hamden	Connecticut
United States	Local Institution	Hewlett	New York
United States	Local Institution	Hickory	North Carolina
United States	Local Institution	Hixson	Tennessee
United States	Local Institution	Houston	Texas
United States	Local Institution	Huntsville	Alabama
United States	Local Institution	Indianapolis	Indiana
United States	Local Institution	Jupiter	Florida
United States	Local Institution	Kansas City	Kansas
United States	Local Institution	Knoxville	Tennessee
United States	Local Institution	La Crosse	Wisconsin
United States	Local Institution	Lake Success	New York
United States	Local Institution	Lansing	Michigan
United States	Local Institution	Largo	Florida
United States	Local Institution	Las Vegas	Nevada
United States	Local Institution	Lebanon	New Hampshire
United States	Local Institution	Long Beach	California
United States	Local Institution	Louisville	Kentucky
United States	Local Institution	Lubbock	Texas
United States	Local Institution	Macon	Georgia
United States	Local Institution	Madison	Wisconsin
United States	Local Institution	Manalapan	New Jersey
United States	Local Institution	Mayfield Village	Ohio
United States	Local Institution	Meadville	Pennsylvania
United States	Local Institution	Mineola	New York
United States	Local Institution	Minneapolis	Minnesota
United States	Local Institution	Morton Grove	Illinois
United States	Local Institution	Myrtle Beach	South Carolina
United States	Local Institution	Nashua	New Hampshire
United States	Local Institution	New Brunswick	New Jersey
United States	Local Institution	New Orleans	Louisiana
United States	Local Institution	New York	New York
United States	Local Institution	Olean	New York
United States	Local Institution	Omaha	Nebraska
United States	Local Institution	Orchard Park	New York
United States	Local Institution	Palm Springs	California
United States	Local Institution	Palo Alto	California
United States	Local Institution	Paradise Valley	Arizona
United States	Local Institution	Peabody	Massachusetts
United States	Local Institution	Peoria	Arizona
United States	Local Institution	Petockey	Michigan
United States	Local Institution	Philadelphia	Pennsylvania
United States	Local Institution	Pittsburgh	Pennsylvania
United States	Local Institution	Portland	Oregon
United States	Local Institution	Prairie Village	Kansas
United States	Local Institution	Providence	Rhode Island
United States	Local Institution	Rochester	New York
United States	Local Institution	Salem	Virginia
United States	Local Institution	San Antonio	Texas
United States	Local Institution	San Diego	California
United States	Local Institution	Santa Monica	California
United States	Local Institution	Sarasota	Florida
United States	Local Institution	Schenectady	New York
United States	Local Institution	Seattle	Washington
United States	Local Institution	Simpsonville	South Carolina
United States	Local Institution	Sioux Falls	South Dakota
United States	Local Institution	Smithtown	New York
United States	Local Institution	Somerset	New Jersey
United States	Local Institution	Springfield	Massachusetts
United States	Local Institution	St. Paul	Minnesota
United States	Local Institution	Sugarland	Texas
United States	Local Institution	Syracuse	New York
United States	Local Institution	Teaneck	New Jersey
United States	Local Institution	Trumbull	Connecticut
United States	Local Institution	Tucson	Arizona
United States	Local Institution	Vancouver	Washington
United States	Local Institution	Voorhees	New Jersey
United States	Local Institution	Washington	District of Columbia
United States	Local Institution	West Reading	Pennsylvania
United States	Local Institution	Wexford	Pennsylvania
United States	Local Institution	Willow Grove	Pennsylvania
United States	Local Institution	Wilmington	North Carolina
United States	Local Institution	Worcester	Massachusetts
United States	Local Institution	Youngstown	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Belgium,  Czech Republic,  France,  Germany,  Ireland,  Italy,  Mexico,  Spain,  United Kingdom, 

References & Publications (1)

Schiff M, Pritchard C, Huffstutter JE, Rodriguez-Valverde V, Durez P, Zhou X, Li T, Bahrt K, Kelly S, Le Bars M, Genovese MC. The 6-month safety and efficacy of abatacept in patients with rheumatoid arthritis who underwent a washout after anti-tumour necrosis factor therapy or were directly switched to abatacept: the ARRIVE trial. Ann Rheum Dis. 2009 Nov;68(11):1708-14. doi: 10.1136/ard.2008.099218. Epub 2008 Dec 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	Days 1-169	Yes
Primary	Short-term Period: Number of Participants With AEs of Special Interest	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).	Days 1-169	Yes
Primary	Short-term Period: Number of Participants With Hematology Laboratories Meeting Marked Abnormality (MA) Criteria	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	Days 1-169	Yes
Primary	Short-term Period: Number of Participants With Liver and Kidney Function Laboratories Meeting MA Criteria	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	Days 1-169	Yes
Primary	Short-term Period: Number of Participants With Electrolyte Laboratories Meeting MA Criteria	Marked abnormality criteria:Sodium (Na): <0.95* LLN/ >1.05* ULN,or if BL	Days 1-169	Yes
Primary	Short-term Period: Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting MA Criteria	Marked abnormality criteria: serum glucose (Glu):<65 mg/dL/ >220 mg/dL; fasting serum Glu: <0.8* LLN/>1.5* ULN, or if BL	Days 1-169	Yes
Primary	Short-term Period: Mean Change From Baseline in Systolic and Diastolic Blood Pressure		Day 1 (Baseline) -Day 169	Yes
Primary	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)	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.	Days 1-169	Yes
Primary	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	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	From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept	Yes
Primary	Long-term Period: Number of Participants With AEs of Special Interest	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).	From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept	Yes
Primary	Long-term Period: Number of Participants With Hematology Laboratories Meeting Marked Abnormality (MA) Criteria	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	From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept	Yes
Primary	Long-term Period: Number of Participants With Liver and Kidney Function Laboratories Meeting MA Criteria	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	From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept	Yes
Primary	Long-term Period: Number of Participants With Electrolyte Laboratories Meeting MA Criteria	Marked abnormality criteria:Sodium (Na): <0.95* LLN/ >1.05* ULN,or if BL	From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept	Yes
Primary	Long-term Period: Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting MA Criteria	Marked abnormality criteria: serum glucose (Glu):<65 mg/dL/ >220 mg/dL; fasting serum Glu: <0.8* LLN/>1.5* ULN, or if BL	From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept	Yes
Primary	Long-term Period: Change From Baseline in Hemoglobin (HGB), Total Protein, and Albumin Over Time	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	BL, Day 365, Day 729	Yes
Primary	Long-term Period: Change From Baseline in Hematocrit Over Time	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).	BL, Day 365, Day 729	Yes
Primary	Long-term Period: Change From Baseline in Erythrocytes Over Time	Erythrocytes NR= 3.80 - 5.50 *10^6 c/uL, MA is <0.75 * BL	BL, Day 365, Day 729	Yes
Primary	Long-term Period: Change From Baseline in Platelets (PLT) Over Time	Erythrocytes NR= 3.80 - 5.50 *10^6 c/uL, MA is <0.75 * BL	BL, Day 365, Day 729	Yes
Primary	Long-term Period: Change From Baseline in White Blood Cells Over Time	Leukocytes NR=4.1 - 12.3*10^3 c/uL, MA is <0.75 * LLN/ >1.25 * ULN, or if BL	BL, Day 365, Day 729	Yes
Primary	Long-term Period: Change From Baseline in Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and G-Glutamyl Transferase (GGT) Over Time	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	BL, Day 365, Day 729	Yes
Primary	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	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	BL, Day 365, Day 729	Yes
Primary	LT; Change From Baseline in Sodium (Na), Potassium (K), Chloride (Cl) Over Time	Na NR=132 - 147 mEq/L, MA is 95* LLN/ >1.05* ULN, or if BL	BL, Day 365, Day 729	Yes
Primary	Long-term Period: Mean Sitting Systolic Blood Pressure (SBP) Over Time	Measurements were taken in a seated position before and after abatacept infusion.	From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept	Yes
Primary	Long-term Period: Mean Sitting Diastolic Blood Pressure (DBP) Over Time	Measurements were taken in a seated position before and after abatacept infusion.	From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept	Yes
Primary	Long-term Period: Mean Heart Rate (HR) Over Time		From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept	Yes
Primary	Long-term Period: Mean Temperature (T) Over Time		From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept	Yes
Secondary	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	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.	BL, Day 169	No
Secondary	Short-term Period: Mean Time-matched Baseline (Day 0) DAS 28 and DAS 28 for Post-Baseline Visits Through 6 Month Open-Label	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.	BL (Day 0), Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169	No
Secondary	Short-term Period: Mean Time-matched Change From Baseline (Day 0) in DAS 28 Through 6 Month Open-Label	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.	BL (Day 0), Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169	No
Secondary	Short-term Period: Mean Change From Baseline to Day 169 in High Sensitivity C-Reactive Protein (Hs-CRP)	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.	BL, Day 169	No
Secondary	Short-term Period: Mean Change From Baseline to Day 169 in Rheumatoid Factor (RF)	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.	BL, Day 169	No
Secondary	Short-term Period: Mean Change From Baseline to Day 169 in the Health Assessment Questionnaire Disability Index (HAQ-DI)	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).	BL, Day 169	No
Secondary	Short-term Period: Number of Participants Achieving a Clinically Meaningful HAQ Response	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.	BL, Day 169	No
Secondary	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	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.	BL	No
Secondary	Short-term Period: Mean Change From Baseline to Day 169 in SF-36 PCS, MCS, and SF-36 Individual Component Scores	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.	BL, Day 169	No
Secondary	Short-term Period: Mean Baseline Fatigue Visual Analog Scale (VAS)	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.	BL	No
Secondary	Short-term Period: Mean Change From Baseline to Day 169 in Fatigue Visual Analog Scale (VAS)	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.	BL, Day 169	No
Secondary	Long-term Period: Number of Participants With Clinically Meaningful Improvement in DAS 28, Low Disease Activity, or Remission Over Time	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.	BL, Days 365, 449, 533, 617, 729, 813	No
Secondary	Long-term Period: Mean Time-matched Baseline (Day 0) DAS 28 and DAS 28 for Post-Baseline Visits Over the Long Term	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.	BL (Day 0), Days 365, 449, 533, 617, 729, 813	No
Secondary	Long-term Period: Mean Time-matched Change From Baseline (Day 0) in DAS 28 Over The Long Term	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.	BL (Day 0), Days 365, 449, 533, 617, 729, 813	No
Secondary	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	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.	BL (Day 0), Days 365, 449, 533, 617, 729, 813	No
Secondary	Long-term Period: Mean Time-matched Change From Baseline (Day 0) in Number of Tender Joints Over the Long Term	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.	BL (Day 0), Days 365, 449, 533, 617, 729, 813	No
Secondary	Long-term Period: Mean Time-matched Baseline (Day 0) Number of Swollen Joints And Post-Baseline Number of Swollen Joints Over the Long Term	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.	BL (Day 0), Days 365, 449, 533, 617, 729, 813	No
Secondary	Long-term Period: Mean Time-Matched Change From Baseline (Day 0) in Number of Swollen Joints Over the Long Term	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.	BL (Day 0), Days 365, 449, 533, 617, 729, 813	No
Secondary	Long-term Period: Mean Time-matched Baseline (Day 0) Hs-CRP Levels and Hs-CRP Levels for Post-Baseline Over the Long Term	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.	BL (Day 0), Days 365, 449, 533, 617, 729, 813	No
Secondary	Long-term Period: Mean Time-matched Change From Baseline (Day 0) in Hs-CRP Level Over the Long Term	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.	BL (Day 0), Days 365, 449, 533, 617, 729, 813	No
Secondary	Long-term Period: Mean Time-matched Baseline (Day 0) Visual Analog Scale (VAS) and VAS for Post-Baseline Visits Over the Long Term	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.	BL (Day 0), Days 365, 449, 533, 617, 729, 813	No
Secondary	Long-term Period: Mean Time-matched Change From Baseline (Day 0) in VAS Over the Long Term	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.	BL (Day 0), Days 365, 449, 533, 617, 729, 813	No
Secondary	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	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.	BL (Day 0)	No
Secondary	Long-term Period: Mean HAQ-DI and HAQ-DI Component Scores For Participant Cohorts at Post-baseline Visits Over the Long Term	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.	Days 365, 449, 533, 617, 729, 813	No
Secondary	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	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.	BL (Day 0), Days 365, 449, 533, 617, 729, 813	No
Secondary	Long-term Period: Number of Participants Achieving Clinically Meaningful HAQ Response Over Time	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.	BL, Days 365, 449, 533, 617, 729, 813	No
Secondary	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	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	BL (Day 0)	No
Secondary	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	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.	Days 365 and 729	No
Secondary	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	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.	BL (Day 0), Days 365, 729	No
Secondary	LT; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by ELISA	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.	Days 1-813	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm