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.

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.

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.

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

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).

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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).

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.