A Phase 3 interventional study of Abatacept (ABA) + Methotrexate (MTX), double-blind (DB) and Infliximab (INF) + MTX, DB in Rheumatoid Arthritis, sponsored by Bristol-Myers Squibb. Completed at 76 sites in 17 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2015-03-24.
Sponsored by Bristol-Myers Squibb · Phase 3, Interventional, and Treatment
The purpose of this clinical research study is to learn if Abatacept or Infliximab in combination with Methotrexate demonstrate a greater reduction in disease activity over placebo.
3,554 studies on the registry are indexed under Arthritis; 318 are open to participants now.
This study's enrollment of 431 is above the median of 90 across 2,377 interventional studies indexed under Arthritis.
Browse Arthritis studies →Bristol-Myers Squibb is the lead sponsor of 1,538 studies on the registry; 116 are open to participants now.
Of its 429 completed or terminated interventional studies of FDA-regulated products, 223 (52%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Days 1-365
Drug: Abatacept (ABA) + Methotrexate (MTX), double-blind (DB)
Days 1-365
Drug: Infliximab (INF) + MTX, DB
Days 1-197
Drug: Placebo (PLA) + MTX, DB
Participants received placebo plus methotrexate for days 1-197, and abatacept plus methotrexate for days 198-365
Drug: PLA + MTX switched to ABA+ MTX, DB
Days 365 to 729 All participants receive Active Drug
Drug: ABA, open-label (OL)
Abatacept, intravenous (IV) Solution, Infusion, Depends on participant weight, Monthly, 12 months.
Also known as: Orencia
Infliximab, IV Solution, Infusion, Depends on participant weight, Every 2 Months, 12 months.
Placebo, IV Solution, Infusion, Depends on participant weight, Monthly, 6 months.
Placebo=IV Solution, Infusion, Depends on participant weight, Monthly, 6 months. Abatacept=IV Solution, Infusion, Depends on participant weight, Monthly, 6 months
Also known as: Orencia
Abatacept, IV solution, Infusion. Depends on participant weight, Monthly, 12+ months
Also known as: Orencia
DB; Adjusted Mean Change From Baseline to Day 197 in Disease Activity Score (DAS) 28 Score (Erythrocyte Sedimentation Rate [ESR]) For ABA Versus PLA (Last Observation Carried Forward [LOCF] Analysis)
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 C-reactive protein (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 is a decrease in DAS28 score of \>1.2 from baseline.
Time frame: Baseline (Day 1), 6 months (Day 197)
OL; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, and AEs Leading to Discontinuation
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. 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.
Time frame: From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)
OL; 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, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
Time frame: From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)
OL; Number of Participants With Select Hematologic Laboratory Abnormalities
High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): \>3 g/dL decrease from Baseline (BL); Hematocrit: \<0.75 x BL; Erythrocytes: \<0.75 x BL; Platelets (PLT): \<0.67 x LLN/\>1.5 x ULN; Leukocytes: \<0.75 x LLN/ \>1.25 x ULN; neutrophils+bands: \<1.0 x 10\^3 c/uL; lymphocytes: \<0.750 x 10\^3 c/uL/ \>7.50 x 10\^3 c/uL; monocytes: \>2000 mm3; eosinophils: \>0.750 x 10\^3 c/uL;
Time frame: From Day 366 through end of OL (range from 1.9 months to 42.3 months)
OL; Number of Participants With Select Blood Chemistry Laboratory Abnormalities
Low=lower than LLN, High=greater than ULN. LLN/ULN= Alkaline phosphatase (ALP): \>2 x ULN; aspartate aminotransferase (AST): \>3 x ULN; alanine aminotransferase (ALT): \>3 x ULN; G-Glutamyl transferase (GGT): \>2 x ULN; Bilirubin: \>2 x ULN; blood urea nitrogen (BUN): \>2 x BL; creatinine: \>4 x BL
Time frame: From Day 366 through end of OL (range from 1.9 months to 42.3 months)
OL; Mean Change From Baseline to Day 365 in Hemoglobin, Total Protein, and Albumin
Hemoglobin (HGB): \>3 g/dL decrease from BL; total protein: \< 0.9 x LLN, \>1.1 x ULN; albumin:\<0.9 x LLN
Time frame: Baseline (Day 1), Day 365
OL; Mean Change From Baseline to Day 365 in Platelets
Platelets (PLT): \<0.67 x LLN, \>1.5 x ULN
Time frame: Baseline (Day 1), Day 365
OL; Mean Change From Baseline to Day 365 in Hematocrit
Hematocrit: \<0.75 x BL
Time frame: Baseline (Day 1), Day 365
OL; Mean Change From Baseline to Day 365 in White Blood Cells
Leukocytes: \<0.75 x LLN, \>1.25 x ULN; neutrophils+bands: \<1.0 x 10\^3 c/uL; eosinophils: \>0.750 x 10\^3 c/uL; basophils: \> 400 mm3; monocytes: \>2000 mm3; lymphocytes: \<0.750 x 10\^3 c/uL, \>7.50 x 10\^3 c/uL.
Time frame: Baseline (Day 1), Day 365
OL; Mean Change From Baseline to Day 365 in Erythrocytes
Erythrocytes: \<0.75 x BL
Time frame: Baseline (Day 1), Day 365
OL; Mean Change From Baseline to Day 365 in Electrolytes
Sodium (Na): \<0.95 x LLN, \>1.05 x ULN; potassium (K): \<0.9 x LLN, \>1.1 x ULN; chloride (Cl): \<0.9 x LLN, \>1.1 x ULN
Time frame: Baseline (Day 1), Day 365
OL; Mean Change From Baseline to Day 365 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Bilirubin: \>2 x ULN; blood urea nitrogen (BUN): \>2 x BL; creatinine: \>4 x BL; calcium (Ca): \<0.8 x LLN, \>1.2 x ULN; phosphorous (P): \<0.75 x LLN, \>1.2 5 x ULN; serum glucose (Glu): \<65 mg/dL, \>220 mg/dL; fasting serum Glu: \<0.8 x LLN, \>1.5 x ULN; uric acid: \>1.5 x ULN;
Time frame: Baseline (Day 1), Day 365
OL; Mean Change From Baseline to Day 365 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
alanine aminotransferase (ALT): \>3 x ULN; aspartate aminotransferase (AST): \>3 x ULN; G-Glutamyl transferase (GGT): \>2 x ULN; Alkaline phosphatase (ALP): \>2 x ULN
Time frame: Baseline (Day 1), Day 365
OL; Mean Change From Baseline to Day 729 in Hemoglobin, Total Protein, and Albumin
Hemoglobin (HGB): \>3 g/dL decrease from BL; total protein: \< 0.9 x LLN, \>1.1 x ULN; albumin:\<0.9 x LLN
Time frame: Baseline (Day 1), Day 729
OL; Mean Change From Baseline to Day 729 in Platelets
Platelets (PLT): \<0.67 x LLN, \>1.5 x ULN
Time frame: Baseline (Day 1), Day 729
OL; Mean Change From Baseline to Day 729 in Hematocrit
Hematocrit: \<0.75 x BL
Time frame: Baseline (Day 1), Day 729
OL; Mean Change From Baseline to Day 729 in White Blood Cells
Leukocytes: \<0.75 x LLN, \>1.25 x ULN; neutrophils+bands: \<1.0 x 10\^3 c/uL; eosinophils: \>0.750 x 10\^3 c/uL; basophils: \> 400 mm3; monocytes: \>2000 mm3; lymphocytes: \<0.750 x 10\^3 c/uL, \>7.50 x 10\^3 c/uL.
Time frame: Baseline (Day 1), Day 729
OL; Mean Change From Baseline to Day 729 in Erythrocytes
Erythrocytes: \<0.75 x BL
Time frame: Baseline (Day 1), Day 729
OL; Mean Change From Baseline to Day 729 in Electrolytes
Sodium (Na): \<0.95 x LLN, \>1.05 x ULN; potassium (K): \<0.9 x LLN, \>1.1 x ULN; chloride (Cl): \<0.9 x LLN, \>1.1 x ULN
Time frame: Baseline (Day 1), Day 729
OL; Mean Change From Baseline to Day 729 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Bilirubin: \>2 x ULN; blood urea nitrogen (BUN): \>2 x BL; creatinine: \>4 x BL; calcium (Ca): \<0.8 x LLN, \>1.2 x ULN; phosphorous (P): \<0.75 x LLN, \>1.2 5 x ULN; serum glucose (Glu): \<65 mg/dL, \>220 mg/dL; fasting serum Glu: \<0.8 x LLN, \>1.5 x ULN; uric acid: \>1.5 x ULN;
Time frame: Baseline (Day 1), Day 729
OL; Mean Change From Baseline to Day 729 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
alanine aminotransferase (ALT): \>3 x ULN; aspartate aminotransferase (AST): \>3 x ULN; G-Glutamyl transferase (GGT): \>2 x ULN; Alkaline phosphatase (ALP): \>2 x ULN
Time frame: Baseline (Day 1), Day 729
OL; Mean Change From Baseline to Day 1121 in Hemoglobin, Total Protein, and Albumin
Hemoglobin (HGB): \>3 g/dL decrease from BL; total protein: \< 0.9 x LLN, \>1.1 x ULN; albumin:\<0.9 x LLN
Time frame: Baseline (Day 1), Day 1121
OL; Mean Change From Baseline to Day 1121 in Platelets
Platelets (PLT): \<0.67 x LLN, \>1.5 x ULN
Time frame: Baseline (Day 1), Day 1121
OL; Mean Change From Baseline to Day 1121 in Hematocrit
Hematocrit: \<0.75 x BL
Time frame: Baseline (Day 1), Day 1121
OL; Mean Change From Baseline to Day 1121 in White Blood Cells
Leukocytes: \<0.75 x LLN, \>1.25 x ULN; neutrophils+bands: \<1.0 x 10\^3 c/uL; eosinophils: \>0.750 x 10\^3 c/uL; basophils: \> 400 mm3; monocytes: \>2000 mm3; lymphocytes: \<0.750 x 10\^3 c/uL, \>7.50 x 10\^3 c/uL.
Time frame: Baseline (Day 1), Day 1121
OL; Mean Change From Baseline to Day 1121 in Erythrocytes
Erythrocytes: \<0.75 x BL
Time frame: Baseline (Day 1), Day 1121
OL; Mean Change From Baseline to Day 1121 in Electrolytes
Sodium (Na): \<0.95 x LLN, \>1.05 x ULN; potassium (K): \<0.9 x LLN, \>1.1 x ULN; chloride (Cl): \<0.9 x LLN, \>1.1 x ULN
Time frame: Baseline (Day 1), Day 1121
OL; Mean Change From Baseline to Day 1121 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Bilirubin: \>2 x ULN; blood urea nitrogen (BUN): \>2 x BL; creatinine: \>4 x BL; calcium (Ca): \<0.8 x LLN, \>1.2 x ULN; phosphorous (P): \<0.75 x LLN, \>1.2 5 x ULN; serum glucose (Glu): \<65 mg/dL, \>220 mg/dL; fasting serum Glu: \<0.8 x LLN, \>1.5 x ULN; uric acid: \>1.5 x ULN;
Time frame: Baseline (Day 1), Day 1121
OL; Mean Change From Baseline to Day 1121 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
alanine aminotransferase (ALT): \>3 x ULN; aspartate aminotransferase (AST): \>3 x ULN; G-Glutamyl transferase (GGT): \>2 x ULN; Alkaline phosphatase (ALP): \>2 x ULN
Time frame: Baseline (Day 1), Day 1121
OL; Mean Change From Baseline to Day 1513 in Hemoglobin, Total Protein, and Albumin
Hemoglobin (HGB): \>3 g/dL decrease from BL; total protein: \< 0.9 x LLN, \>1.1 x ULN; albumin:\<0.9 x LLN
Time frame: Baseline (Day 1), Day 1513
OL; Mean Change From Baseline to Day 1513 in Platelets
Platelets (PLT): \<0.67 x LLN, \>1.5 x ULN
Time frame: Baseline (Day 1), Day 1513
OL; Mean Change From Baseline to Day 1513 in Hematocrit
Hematocrit: \<0.75 x BL
Time frame: Baseline (Day 1), Day 1513
OL; Mean Change From Baseline to Day 1513 in White Blood Cells
Leukocytes: \<0.75 x LLN, \>1.25 x ULN; neutrophils+bands: \<1.0 x 10\^3 c/uL; eosinophils: \>0.750 x 10\^3 c/uL; basophils: \> 400 mm3; monocytes: \>2000 mm3; lymphocytes: \<0.750 x 10\^3 c/uL, \>7.50 x 10\^3 c/uL.
Time frame: Baseline (Day 1), Day 1513
OL; Mean Change From Baseline to Day 1513 in Erythrocytes
Erythrocytes: \<0.75 x BL
Time frame: Baseline (Day 1), Day 1513
OL; Mean Change From Baseline to Day 1513 in Electrolytes
Sodium (Na): \<0.95 x LLN, \>1.05 x ULN; potassium (K): \<0.9 x LLN, \>1.1 x ULN; chloride (Cl): \<0.9 x LLN, \>1.1 x ULN
Time frame: Baseline (Day 1), Day 1513
OL; Mean Change From Baseline to Day 1513 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Bilirubin: \>2 x ULN; blood urea nitrogen (BUN): \>2 x BL; creatinine: \>4 x BL; calcium (Ca): \<0.8 x LLN, \>1.2 x ULN; phosphorous (P): \<0.75 x LLN, \>1.2 5 x ULN; serum glucose (Glu): \<65 mg/dL, \>220 mg/dL; fasting serum Glu: \<0.8 x LLN, \>1.5 x ULN; uric acid: \>1.5 x ULN;
Time frame: Baseline (Day 1), Day 1513
OL; Mean Change From Baseline to Day 1513 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
alanine aminotransferase (ALT): \>3 x ULN; aspartate aminotransferase (AST): \>3 x ULN; G-Glutamyl transferase (GGT): \>2 x ULN; Alkaline phosphatase (ALP): \>2 x ULN
Time frame: Baseline (Day 1), Day 1513
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP), units=mm mercury (Hg)
Time frame: Days 365, 729, 1121, and 1513
OL; Mean Heart Rate (HR) During Open Label Period
Heart Rate (HR), units=beats per minute (bpm)
Time frame: Days 365, 729, 1121, and 1513
OL; Mean Temperature (T) During Open Label Period
Temperature (T), units=degrees Celcius
Time frame: Days 365, 729, 1121, and 1513
DB; Adjusted Mean Change From Baseline to Day 197 in DAS 28 Score (ESR) For INF Versus PLA (LOCF Analysis)
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 is a decrease in DAS28 score of \>1.2 from baseline.
Time frame: Baseline (Day 1), 6 months (Day 197)
DB; DAS 28 (ESR) Area Under The Curve (AUC) Over 12 Months For ABA Versus INF
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). Clinically significant response= decrease in DAS28 score of \>1.2 from baseline. DAS28 AUC can be calculated from the DAS28 score versus time curve, which provides an assessment of changes in disease activity over time.
Time frame: From Day 1 through Day 365 (12 months)
DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 197
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.
Time frame: DB Day 197
DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 365
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.
Time frame: DB Day 365
DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis)
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.
Time frame: Baseline (Day 1), 6 months (Day 197)
DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis)
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.
Time frame: Baseline (Day 1), 12 months (Day 365)
DB; Adjusted Mean Change From Baseline to Day 197 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)
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.
Time frame: Baseline (Day 1), 6 months (Day 197)
DB; Adjusted Mean Change From Baseline to Day 365 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)
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.
Time frame: Baseline (Day 1), 12 months (Day 365)
DB; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) at Day 365
The DAS28 is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= \> 5.1, low disease activity= \< 3.2, and remission= \< 2.6. Clinically significant response= decrease of \>1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute: \<3.2 or \>1.2 improvement from baseline \[BL\]), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: \>5.1 or \<0.6 change from BL)
Time frame: DB Day 365
DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 197
The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein \[CRP\]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.
Time frame: DB Day 197
DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 365
The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein \[CRP\]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.
Time frame: DB Day 365
DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, and AEs Leading to Discontinuation From Day 1 Through Day 197
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. 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.
Time frame: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 197
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, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
Time frame: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, and AEs Leading to Discontinuation From Day 1 Through Day 365
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. 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.
Time frame: From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, and AEs Leading to Discontinuation From Day 198 Through Day 365 in Participants Receiving Placebo Switched to Abatacept
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. 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.
Time frame: From Day 198 through Day 365, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 365
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, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
Time frame: From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With AEs of Special Interest From Day 198 Through Day 365 in Participants Receiving Placebo Switched to Abatacept
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, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
Time frame: From Day 198 through Day 365, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With Significant Changes in Mean Systolic and Diastolic Blood Pressure During Days 1 Through 197 and Days 1 Through 365
Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
Time frame: From Baseline (Day 1) through Day 197, or Day 1 through Day 365, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With Significant Changes in Mean Heart Rate During Days 1 Through 197 and Days 1 Through 365
Heart Rate (HR) was assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
Time frame: From Baseline (Day 1) through Day 197, or Day 1 through Day 365, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With Significant Changes in Mean Temperature During Days 1 Through 197 and Days 1 Through 365
Temperature (T) was assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
Time frame: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197
High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): \>3 g/dL decrease from Baseline (BL); Hematocrit: \<0.75 x BL; Platelets (PLT): \<0.67 x LLN/\>1.5 x ULN; Leukocytes: \<0.75 x LLN/ \>1.25 x ULN; neutrophils+bands: \<1.0 x 10\^3 c/uL; aspartate aminotransferase (AST): \>3 x ULN; alanine aminotransferase (ALT): \>3 x ULN; creatinine: \>4 x BL
Time frame: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365
High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): \>3 g/dL decrease from Baseline (BL); Hematocrit: \<0.75 x BL; Platelets (PLT): \<0.67 x LLN/\>1.5 x ULN; Leukocytes: \<0.75 x LLN/ \>1.25 x ULN; neutrophils+bands: \<1.0 x 10\^3 c/uL; aspartate aminotransferase (AST): \>3 x ULN; alanine aminotransferase (ALT): \>3 x ULN; creatinine: \>4 x BL
Time frame: From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With Anti-Abatacept Antibodies From Day 1 Through Day 365 (Electrochemiluminescent [ECL] Immunoassay)
ECL screened sera for drug-specific antibodies, immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction Category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing.
Time frame: Day 1 through day 365
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Infliximab levels were measured using a microplate enzyme-linked immunosorbant assay (ELISA) with infliximab bound to immobilized recombinant tumor necrosis factor (TNF)-alpha. Bound infliximab is detected utilizing a horseradish peroxidase-conjugated anti-human IgG Fc(fragment, crystallizable region)-specific). The enzyme turns over the substrate O-phenlenediamine to a chromogenic product that is measured at 490 nm. The cut-off value was 1.40 ug/mL; this was based on the mean (+ 3 SD) value in serum samples from 40 participants who had never received infliximab.
Time frame: Day 1 through day 365
OL; Mean Change From Baseline Over Time in DAS 28 (ESR) Score
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 is a decrease in DAS28 score of \>1.2 from baseline.
Time frame: Baseline (Day 1), Day 365, Day 533, Day 729
OL; Percentage of Participants With DAS28 (ESR) Remission and Low Disease Activity (LDAS) 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 is a decrease in DAS28 score of \>1.2 from baseline.
Time frame: Baseline (Day 1), Day 365, Day 533, Day 729
OL; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Over Time
The DAS28 is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= \> 5.1, low disease activity= \< 3.2, and remission= \< 2.6. Clinically significant response= decrease of \>1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute \<3.2 or \>1.2 improvement from baseline \[BL\]), moderate (absolute 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute \>5.1 or \<0.6 change from BL)
Time frame: DB Days 365, 533, and 729
OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time
The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein \[CRP\]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.
Time frame: DB Day 197, Day 365, Day 533, Day 729
OL; Percentage of Participants Who Achieved Major Clinical Response
Major Clinical Response was defined as a continuous ACR 70 for six months.
Time frame: Defined from the date of achieving ACR 70 response to 6 months post response
OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time
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.
Time frame: OL Days 197, 253, 281, 309, 337, 365, 449, 533, 617, and 729
OL; Adjusted Mean Change From Baseline to Day 729 in HAQ-DI
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.
Time frame: Day 1 (Baseline), Day 729
| Milestone | Abatacept (ABA) + Methotrexate (MTX) [Double-blind (DB)] | Infliximab (INF) + MTX [DB] | Placebo (PLA) + MTX [DB] | PLA Switched to ABA + MTX [DB] | ABA + MTX [Open-label (OL)] |
|---|---|---|---|---|---|
| Started | 156 | 165 | 110 | 0 | 0 |
| Completed | 147 | 152 | 107 | 0 | 0 |
| Not completed | 9 | 13 | 3 | 0 | 0 |
| Withdrew: Death | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Adverse event | 2 | 8 | 1 | 0 | 0 |
| Withdrew: Lack of efficacy | 2 | 2 | 1 | 0 | 0 |
| Withdrew: Lost to follow-up | 2 | 2 | 0 | 0 | 0 |
| Withdrew: Withdrawal of consent | 1 | 0 | 1 | 0 | 0 |
| Withdrew: Pregnancy | 1 | 1 | 0 | 0 | 0 |
| Milestone | Abatacept (ABA) + Methotrexate (MTX) [Double-blind (DB)] | Infliximab (INF) + MTX [DB] | Placebo (PLA) + MTX [DB] | PLA Switched to ABA + MTX [DB] | ABA + MTX [Open-label (OL)] |
|---|---|---|---|---|---|
| Started | 147 | 152 | 0 | 107 | 0 |
| Completed | 139 | 141 | 0 | 104 | 0 |
| Not completed | 8 | 11 | 0 | 3 | 0 |
| Withdrew: Death | 0 | 1 | 0 | 1 | 0 |
| Withdrew: Adverse event | 2 | 4 | 0 | 0 | 0 |
| Withdrew: Lack of efficacy | 2 | 4 | 0 | 1 | 0 |
| Withdrew: Withdrawal of consent | 3 | 2 | 0 | 0 | 0 |
| Withdrew: Participant relocation | 1 | 0 | 0 | 1 | 0 |
| Milestone | Abatacept (ABA) + Methotrexate (MTX) [Double-blind (DB)] | Infliximab (INF) + MTX [DB] | Placebo (PLA) + MTX [DB] | PLA Switched to ABA + MTX [DB] | ABA + MTX [Open-label (OL)] |
|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 372 |
| Completed | 0 | 0 | 0 | 0 | 327 |
| Not completed | 0 | 0 | 0 | 0 | 45 |
| Withdrew: Death | 0 | 0 | 0 | 0 | 3 |
| Withdrew: Adverse event | 0 | 0 | 0 | 0 | 11 |
| Withdrew: Lack of efficacy | 0 | 0 | 0 | 0 | 9 |
| Withdrew: Lost to follow-up | 0 | 0 | 0 | 0 | 6 |
| Withdrew: Withdrawal of consent | 0 | 0 | 0 | 0 | 12 |
| Withdrew: Pregnancy | 0 | 0 | 0 | 0 | 1 |
| Withdrew: No longer meets study criteria | 0 | 0 | 0 | 0 | 1 |
| Withdrew: Participant chose to use revellex | 0 | 0 | 0 | 0 | 1 |
| Withdrew: Leaving country | 0 | 0 | 0 | 0 | 1 |
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 C-reactive protein (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 is a decrease in DAS28 score of \>1.2 from baseline.
| units on a scale | ABA + MTX [DB] | PLA + MTX [DB] |
|---|---|---|
| DB; Adjusted Mean Change From Baseline to Day 197 in Disease Activity Score (DAS) 28 Score (Erythrocyte Sedimentation Rate [ESR]) For ABA Versus PLA (Last Observation Carried Forward [LOCF] Analysis) | -2.53 ± 0.12 | -1.48 ± 0.15 |
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 is a decrease in DAS28 score of \>1.2 from baseline.
| units on a scale | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|
| DB; Adjusted Mean Change From Baseline to Day 197 in DAS 28 Score (ESR) For INF Versus PLA (LOCF Analysis) | -2.25 ± 0.12 | -1.48 ± 0.15 |
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). Clinically significant response= decrease in DAS28 score of \>1.2 from baseline. DAS28 AUC can be calculated from the DAS28 score versus time curve, which provides an assessment of changes in disease activity over time.
| units on a scale | ABA + MTX [DB[ | INF + MTX [DB] |
|---|---|---|
| DB; DAS 28 (ESR) Area Under The Curve (AUC) Over 12 Months For ABA Versus INF | 1638.6 ± 395.81 | 1657.5 ± 460.52 |
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.
| percentage of participants | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 197 | 61.5 | 58.8 | 40.9 |
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.
| percentage of participants | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 365 | 57.7 | 52.7 | 57.3 |
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.
| units on a scale | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| HAQ-DI | -0.69 ± 0.05 | -0.61 ± 0.05 | -0.31 ± 0.06 |
| HAQ-DI component: activities | -0.61 ± 0.06 | -0.54 ± 0.06 | -0.22 ± 0.08 |
| HAQ-DI component: dressing and grooming | -0.69 ± 0.06 | -0.57 ± 0.06 | -0.37 ± 0.07 |
| HAQ-DI component: eating | -0.79 ± 0.06 | -0.77 ± 0.06 | -0.36 ± 0.08 |
| HAQ-DI component: grip | -0.73 ± 0.07 | -0.70 ± 0.07 | -0.26 ± 0.08 |
| HAQ-DI component: hygiene | -0.64 ± 0.07 | -0.48 ± 0.07 | -0.26 ± 0.08 |
| HAQ-DI component: reach | -0.72 ± 0.07 | -0.64 ± 0.07 | -0.30 ± 0.08 |
| HAQ-DI component: arising | -0.70 ± 0.06 | -0.68 ± 0.06 | -0.39 ± 0.07 |
| HAQ-DI component: walking | -0.58 ± 0.06 | -0.56 ± 0.06 | -0.23 ± 0.07 |
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.
| units on a scale | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| HAQ-DI | -0.67 ± 0.05 | -0.59 ± 0.05 | -0.56 ± 0.06 |
| HAQ-DI component: activities | -0.55 ± 0.07 | -0.52 ± 0.07 | -0.55 ± 0.08 |
| HAQ-DI component: dressing and grooming | -0.72 ± 0.06 | -0.60 ± 0.06 | -0.56 ± 0.07 |
| HAQ-DI component: eating | -0.80 ± 0.06 | -0.73 ± 0.06 | -0.71 ± 0.08 |
| HAQ-DI component: grip | -0.77 ± 0.07 | -0.64 ± 0.07 | -0.56 ± 0.08 |
| HAQ-DI component: hygiene | -0.53 ± 0.07 | -0.45 ± 0.07 | -0.42 ± 0.09 |
| HAQ-DI component: reach | -0.77 ± 0.07 | -0.66 ± 0.07 | -0.53 ± 0.08 |
| HAQ-DI component: arising | -0.68 ± 0.06 | -0.64 ± 0.06 | -0.61 ± 0.07 |
| HAQ-DI component: walking | -0.54 ± 0.06 | -0.55 ± 0.06 | -0.47 ± 0.07 |
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.
| units on a scale | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| SF-36 Physical Component Summary | 8.36 ± 0.69 | 7.66 ± 0.67 | 4.34 ± 0.82 |
| SF-36 Mental Component Summary | 5.14 ± 0.79 | 4.32 ± 0.76 | 1.64 ± 0.93 |
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.
| units on a scale | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| SF-36 Physical Component Summary | 9.52 ± 0.70 | 7.59 ± 0.68 | 8.00 ± 0.83 |
| SF-36 Mental Component Summary | 5.96 ± 0.81 | 4.03 ± 0.79 | 5.85 ± 0.97 |
The DAS28 is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= \> 5.1, low disease activity= \< 3.2, and remission= \< 2.6. Clinically significant response= decrease of \>1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute: \<3.2 or \>1.2 improvement from baseline \[BL\]), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: \>5.1 or \<0.6 change from BL)
| percentage of participants | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| No response | 27.3 | 36.3 | 23.5 |
| Moderate response | 40.7 | 45.2 | 49.0 |
| Good response | 32.0 | 18.5 | 27.5 |
The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein \[CRP\]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.
| percentage of participants | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Day 197, ACR 20 | 66.7 | 59.4 | 41.8 |
| Day 197, ACR 50 | 40.4 | 37.0 | 20.0 |
| Day 197, ACR 70 | 20.5 | 24.2 | 9.1 |
The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein \[CRP\]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.
| percentage of participants | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Day 365, ACR 20 | 72.4 | 55.8 | 68.2 |
| Day 365, ACR 50 | 45.5 | 36.4 | 50.9 |
| Day 365, ACR 70 | 26.3 | 20.6 | 29.1 |
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. 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.
| participants | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Deaths | 1 | 1 | 0 |
| SAEs | 8 | 19 | 13 |
| Related SAEs | 3 | 8 | 3 |
| SAEs Leading to Discontinuation | 2 | 4 | 0 |
| AEs | 129 | 140 | 92 |
| Related AEs | 64 | 74 | 46 |
| AEs Leading to discontinuation | 3 | 8 | 1 |
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, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
| participants | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Pre-specified infections | 12 | 18 | 8 |
| Neoplasms: Benign, malignant, and unspecified | 1 | 2 | 1 |
| Prespecified autoimmune symptoms and disorders | 1 | 1 | 1 |
| Pre-specified infusional AEs | 8 | 30 | 11 |
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. 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.
| participants | ABA + MTX [DB] | INF + MTX [DB] |
|---|---|---|
| Deaths | 1 | 2 |
| SAEs | 15 | 30 |
| Related SAEs | 5 | 14 |
| SAEs Leading to Discontinuation | 4 | 6 |
| AEs | 139 | 154 |
| Related AEs | 72 | 96 |
| AEs Leading to discontinuation | 5 | 12 |
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. 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.
| participants | PLA Switched to ABA + MTX [DB] |
|---|---|
| Deaths | 1 |
| SAEs | 12 |
| Related SAEs | 3 |
| SAEs Leading to Discontinuation | 0 |
| AEs | 71 |
| Related AEs | 26 |
| AEs Leading to discontinuation | 0 |
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. 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.
| participants | ABA + MTX [OL] |
|---|---|
| Deaths | 3 |
| SAEs | 90 |
| Related SAEs | 12 |
| SAEs Leading to Discontinuation | 5 |
| AEs | 349 |
| Related AEs | 165 |
| AEs Leading to discontinuation | 10 |
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, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
| participants | ABA + MTX [OL] |
|---|---|
| Infections | 277 |
| Malignant neoplasms | 3 |
| Benign and unspecified neoplasms | 18 |
| Prespecified autoimmune symptoms and disorders | 13 |
| Pre-specified peri-infusional AEs | 50 |
| Pre-specified acute infusional AEs | 28 |
High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): \>3 g/dL decrease from Baseline (BL); Hematocrit: \<0.75 x BL; Erythrocytes: \<0.75 x BL; Platelets (PLT): \<0.67 x LLN/\>1.5 x ULN; Leukocytes: \<0.75 x LLN/ \>1.25 x ULN; neutrophils+bands: \<1.0 x 10\^3 c/uL; lymphocytes: \<0.750 x 10\^3 c/uL/ \>7.50 x 10\^3 c/uL; monocytes: \>2000 mm3; eosinophils: \>0.750 x 10\^3 c/uL;
| participants | ABA + MTX [OL] |
|---|---|
| Low HGB (>3g/dL decrease from BL), n=372 | 9 |
| Low hematocrit (< 0.75 x BL), n=372 | 7 |
| Low erythrocytes (<0.75 x BL), n=372 | 6 |
| Low PLT (<0.67 x LLN), n=370 | 2 |
| High leukocytes (>1.25 x ULN), n=372 | 29 |
| Low neutrophils + bands (<1.0 x 10^3 c/uL), n=372 | 1 |
| Low lymphocytes (<0.75 x 10^3 c/uL), n=372 | 12 |
| High monocytes (>2000/mm^3), n=372 | 3 |
| High eosinophils (>0.750 x 10^3 c/uL), n=372 | 15 |
Low=lower than LLN, High=greater than ULN. LLN/ULN= Alkaline phosphatase (ALP): \>2 x ULN; aspartate aminotransferase (AST): \>3 x ULN; alanine aminotransferase (ALT): \>3 x ULN; G-Glutamyl transferase (GGT): \>2 x ULN; Bilirubin: \>2 x ULN; blood urea nitrogen (BUN): \>2 x BL; creatinine: \>4 x BL
| participants | ABA + MTX [OL] |
|---|---|
| High ALP (>2 x ULN) | 1 |
| High AST (>3 x ULN) | 4 |
| High ALT (>3 x ULN) | 11 |
| High GGT (>2 x ULN) | 16 |
| High total bilirubin (>2 x ULN) | 1 |
| High BUN (>2 x BL) | 17 |
| High creatinine (>1.5 increase from BL) | 44 |
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, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
| participants | ABA + MTX [DB] | INF + MTX [DB] |
|---|---|---|
| Pre-specified infections | 16 | 30 |
| Neoplasms:Benign, malignant, and unspecified | 1 | 2 |
| Prespecified autoimmune symptoms and disorders | 2 | 1 |
| Pre-specified infusional AEs | 11 | 41 |
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, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
| participants | PLA Switched to ABA + MTX [DB] |
|---|---|
| Pre-specified infections | 3 |
| Prespecified autoimmune symptoms and disorders | 1 |
| Pre-specified infusional AEs | 5 |
Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
| participants | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Days 1-197 | 0 | 0 | 0 |
| Days 1-365 | 0 | 0 | 0 |
Heart Rate (HR) was assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
| participants | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Days 1-197 | 0 | 0 | 0 |
| Days 1-365 | 0 | 0 | 0 |
Temperature (T) was assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
| participants | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Days 1-197 | 0 | 0 | 0 |
| Days 1-365 | 0 | 0 | 0 |
High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): \>3 g/dL decrease from Baseline (BL); Hematocrit: \<0.75 x BL; Platelets (PLT): \<0.67 x LLN/\>1.5 x ULN; Leukocytes: \<0.75 x LLN/ \>1.25 x ULN; neutrophils+bands: \<1.0 x 10\^3 c/uL; aspartate aminotransferase (AST): \>3 x ULN; alanine aminotransferase (ALT): \>3 x ULN; creatinine: \>4 x BL
| participants | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Low HGB (n=155, n=162, n=108) | 1 | 1 | 1 |
| Low hematocrit (n=155, n=162, n=108) | 0 | 2 | 0 |
| Low PLT (n=154, n=160, n=108) | 1 | 2 | 0 |
| High PLT (n=154, n=160, n=108) | 0 | 0 | 1 |
| Low leukocytes (n=155, n=162, n=108) | 0 | 1 | 0 |
| High leukocytes (n=155, n=162, n=108) | 6 | 12 | 16 |
| Low neutrophils + bands (n=155, n=162, n=108) | 0 | 0 | 1 |
| High AST (n=155, n=162, n=108) | 3 | 3 | 1 |
| High ALT (n=155, n=162, n=108) | 3 | 2 | 3 |
| High creatinine (n=155, n=162, n=108) | 6 | 9 | 5 |
High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): \>3 g/dL decrease from Baseline (BL); Hematocrit: \<0.75 x BL; Platelets (PLT): \<0.67 x LLN/\>1.5 x ULN; Leukocytes: \<0.75 x LLN/ \>1.25 x ULN; neutrophils+bands: \<1.0 x 10\^3 c/uL; aspartate aminotransferase (AST): \>3 x ULN; alanine aminotransferase (ALT): \>3 x ULN; creatinine: \>4 x BL
| participants | ABA + MTX [DB] | INF + MTX [DB] | PLA Switched to ABA + MTX [DB] |
|---|---|---|---|
| Low HGB (n=156, n=164, n=109) | 2 | 1 | 1 |
| Low hematocrit (n=156, n=164, n=109) | 1 | 2 | 0 |
| Low PLT (n=155, n=162, n=109) | 1 | 2 | 0 |
| High PLT (n=155, n=162, n=109) | 0 | 0 | 1 |
| Low leukocytes (n=156, n=164, n=109) | 0 | 1 | 0 |
| High leukocytes (n=156, n=164, n=109) | 7 | 22 | 20 |
| Low neutrophils + bands (n=156, n=164, n=109) | 0 | 0 | 1 |
| High AST (n=156, n=164, n=109) | 4 | 6 | 3 |
| High ALT (n=156, n=164, n=109) | 3 | 7 | 5 |
| High creatinine (n=156, n=164, n=109) | 10 | 13 | 7 |
ECL screened sera for drug-specific antibodies, immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction Category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing.
| participants | ABA + MTX [DB] | PLA Switched to ABA + MTX [DB] |
|---|---|---|
| CTLA4 and Possibly Ig | 0 | 0 |
| Ig and/or Junction | 0 | 0 |
Infliximab levels were measured using a microplate enzyme-linked immunosorbant assay (ELISA) with infliximab bound to immobilized recombinant tumor necrosis factor (TNF)-alpha. Bound infliximab is detected utilizing a horseradish peroxidase-conjugated anti-human IgG Fc(fragment, crystallizable region)-specific). The enzyme turns over the substrate O-phenlenediamine to a chromogenic product that is measured at 490 nm. The cut-off value was 1.40 ug/mL; this was based on the mean (+ 3 SD) value in serum samples from 40 participants who had never received infliximab.
| percentage of participants | INF + MTX [DB] |
|---|---|
| Overall anti-HACA | 62.0 |
| Overall indeterminate anti-HACA | 73.0 |
| Day 1 anti-HACA | 0 |
| Day 1 indeterminate anti-HACA | 3.7 |
| Day 113 anti-HACA | 20.0 |
| Day 113 indeterminate anti-HACA | 74.7 |
| Day 197 anti-HACA | 42.2 |
| Day 197 indeterminate anti-HACA | 33.3 |
| Day 309 anti-HACA | 53.6 |
| Day 309 indeterminate anti-HACA | 29.7 |
| Post Day 28 anti-HACA | 52.2 |
| Post Day 28 indeterminate anti-HACA | 27.5 |
| Discontinued, overall anti-HACA | 60.9 |
| Discontinued, overall indeterminate anti-HACA | 47.8 |
| Discontinued, post day 28 anti-HACA | 55.0 |
| Discontinued, post day 28 indeterminate anti-HACA | 25.0 |
| Discontinued, post day 56 anti-HACA | 72.7 |
| Discontinued, post day 56 indeterminate anti-HACA | 9.1 |
| Discontinued, post day 85 anti-HACA | 88.9 |
| Discontinued, post day 85 indeterminate anti-HACA | 0 |
| Missed doses, overall anti-HACA | 73.1 |
| Missed doses, overall indeterminate anti-HACA | 76.9 |
| Missed 1 dose, anti-HACA | 72.0 |
| Missed 1 dose, indeterminate anti-HACA | 76.0 |
| Missed >1 dose, anti-HACA | 100.0 |
| Missed >1 dose, indeterminate anti-HACA | 100.0 |
Hemoglobin (HGB): \>3 g/dL decrease from BL; total protein: \< 0.9 x LLN, \>1.1 x ULN; albumin:\<0.9 x LLN
| g/dL | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| HGB (n=131, n=135, n=103) | 0.53 ± 0.09 | 0.24 ± 0.09 | 0.43 ± 0.09 |
| Total protein (n=131, n=136, n=104) | -0.09 ± 0.04 | 0.11 ± 0.04 | -0.12 ± 0.04 |
| Albumin (n=131, n=136, n=104) | 0.12 ± 0.03 | 0.00 ± 0.03 | 0.05 ± 0.03 |
Platelets (PLT): \<0.67 x LLN, \>1.5 x ULN
| 10^9 c/L | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| OL; Mean Change From Baseline to Day 365 in Platelets | -42.4 ± 5.20 | -35.5 ± 6.93 | -28.4 ± 6.75 |
Hematocrit: \<0.75 x BL
| percentage red blood cells | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| OL; Mean Change From Baseline to Day 365 in Hematocrit | 1.44 ± 0.29 | 0.51 ± 0.27 | 1.03 ± 0.27 |
Leukocytes: \<0.75 x LLN, \>1.25 x ULN; neutrophils+bands: \<1.0 x 10\^3 c/uL; eosinophils: \>0.750 x 10\^3 c/uL; basophils: \> 400 mm3; monocytes: \>2000 mm3; lymphocytes: \<0.750 x 10\^3 c/uL, \>7.50 x 10\^3 c/uL.
| 10^3 c/uL | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Leukocytes (n=131, n=134, n=103) | -0.95 ± 0.23 | -0.90 ± 0.21 | -0.84 ± 0.23 |
| Neutrophils + bands (n=130, n=130, n=104) | -0.91 ± 0.20 | -1.14 ± 0.20 | -1.05 ± 0.22 |
| Basophils (n=130, n=130, n=101) | -0.01 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 |
| Monocytes (n=130, n=130, n=101) | -0.01 ± 0.02 | -0.01 ± 0.02 | 0.02 ± 0.02 |
| Eosinophils (n=130, n=130, n=101) | -0.04 ± 0.01 | -0.02 ± 0.02 | -0.03 ± 0.01 |
| Lymphocytes (n=130, n=130, n=101) | 0.03 ± 0.07 | 0.24 ± 0.06 | 0.22 ± 0.08 |
Erythrocytes: \<0.75 x BL
| 10^6 c/uL | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| OL; Mean Change From Baseline to Day 365 in Erythrocytes | 0.09 ± 0.03 | 0.00 ± 0.03 | 0.006 ± 0.03 |
Sodium (Na): \<0.95 x LLN, \>1.05 x ULN; potassium (K): \<0.9 x LLN, \>1.1 x ULN; chloride (Cl): \<0.9 x LLN, \>1.1 x ULN
| mEq/L | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Na (n=131, n=136, n=104) | -1.62 ± 0.29 | -1.57 ± 0.33 | -1.09 ± 0.38 |
| K (n=131, n=135, n=104) | -0.03 ± 0.04 | -0.07 ± 0.04 | -0.03 ± 0.05 |
| Cl (n=131, n=136, n=104) | -1.40 ± 0.28 | -1.18 ± 0.31 | -1.06 ± 0.33 |
Bilirubin: \>2 x ULN; blood urea nitrogen (BUN): \>2 x BL; creatinine: \>4 x BL; calcium (Ca): \<0.8 x LLN, \>1.2 x ULN; phosphorous (P): \<0.75 x LLN, \>1.2 5 x ULN; serum glucose (Glu): \<65 mg/dL, \>220 mg/dL; fasting serum Glu: \<0.8 x LLN, \>1.5 x ULN; uric acid: \>1.5 x ULN;
| mg/dL | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Creatinine (n=131, n=136, n=104) | 0.03 ± 0.02 | 0.02 ± 0.01 | 0.01 ± 0.02 |
| BUN (n=131, n=136, n=104) | -0.31 ± 0.41 | -0.52 ± 0.40 | 0.10 ± 0.53 |
| Ca (n=131, n=136, n=104) | 0.14 ± 0.04 | 0.08 ± 0.03 | 0.14 ± 0.04 |
| P (n=131, n=136, n=104) | 0.03 ± 0.05 | -0.01 ± 0.05 | 0.05 ± 0.05 |
| Uric Acid (n=131, n=136, n=104) | 0.09 ± 0.08 | 0.08 ± 0.10 | 0.04 ± 0.12 |
| Total bilirubin (n=131, n=134, n=104) | 0.06 ± 0.01 | 0.04 ± 0.02 | 0.03 ± 0.02 |
| Serum glucose (n=131, n=136, n=104) | 5.66 ± 2.41 | 2.49 ± 3.15 | 3.03 ± 2.16 |
alanine aminotransferase (ALT): \>3 x ULN; aspartate aminotransferase (AST): \>3 x ULN; G-Glutamyl transferase (GGT): \>2 x ULN; Alkaline phosphatase (ALP): \>2 x ULN
| U/L | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| ALT (n=131, n=135, n=104) | 3.51 ± 1.33 | 2.19 ± 2.31 | -0.04 ± 1.68 |
| AST (n=131, n=135, n=104) | 0.54 ± 1.04 | -0.11 ± 1.51 | -2.23 ± 1.41 |
| GGT (n=131, n=135, n=104) | 2.53 ± 2.81 | -0.61 ± 1.76 | -2.32 ± 2.73 |
| ALP (n=131, n=136, n=104) | -0.53 ± 2.16 | -7.78 ± 2.24 | -4.34 ± 2.48 |
Hemoglobin (HGB): \>3 g/dL decrease from BL; total protein: \< 0.9 x LLN, \>1.1 x ULN; albumin:\<0.9 x LLN
| g/dL | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| HGB (n=124, n=125, n=102) | 0.66 ± 0.10 | 0.48 ± 0.10 | 0.40 ± 0.13 |
| Total protein (n=124, n=127, n=102) | -0.33 ± 0.05 | -0.25 ± 0.04 | -0.29 ± 0.05 |
| Albumin (n=124, n=127, n=102) | 0.13 ± 0.03 | 0.10 ± 0.03 | 0.06 ± 0.03 |
Platelets (PLT): \<0.67 x LLN, \>1.5 x ULN
| 10^9 c/L | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| OL; Mean Change From Baseline to Day 729 in Platelets | -63.9 ± 6.04 | -5832 ± 7.66 | -47.7 ± 8.16 |
Hematocrit: \<0.75 x BL
| percentage of red blood cells | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| OL; Mean Change From Baseline to Day 729 in Hematocrit | 1.72 ± 0.29 | 1.23 ± 0.29 | 0.99 ± 0.38 |
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 is a decrease in DAS28 score of \>1.2 from baseline.
| units on a scale | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Day 365 (n=122, n=130, n=94) | -3.12 ± 0.13 | -2.39 ± 0.13 | -2.81 ± 0.16 |
| Day 533 (n=118, n=121, n=92) | -3.21 ± 0.13 | -3.04 ± 0.13 | -2.84 ± 0.17 |
| Day 729 (n=110, n=121, n=93) | -3.35 ± 0.14 | -3.29 ± 0.12 | -2.98 ± 0.17 |
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 is a decrease in DAS28 score of \>1.2 from baseline.
| percentage of participants | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Day 365 Remission (n=127, n=135, n=102) | 19.7 | 13.3 | 15.7 |
| Day 365 LDAS (n=127, n=135, n=102) | 37.0 | 23.0 | 29.4 |
| Day 533 Remission (n=122, n=125, n=98) | 20.5 | 20.0 | 19.4 |
| Day 533 LDAS (n=122, n=125, n=98) | 37.7 | 33.6 | 35.7 |
| Day 729 Remission (n=115, n=126, n=100) | 26.1 | 28.6 | 22.0 |
| Day 729 LDAS (n=115, n=126, n=100) | 41.7 | 45.2 | 34.0 |
The DAS28 is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= \> 5.1, low disease activity= \< 3.2, and remission= \< 2.6. Clinically significant response= decrease of \>1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute \<3.2 or \>1.2 improvement from baseline \[BL\]), moderate (absolute 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute \>5.1 or \<0.6 change from BL)
| percentage of participants | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Day 365 Good response (n=122, n=130, n=94) | 38.5 | 23.1 | 30.9 |
| Day 365 Moderate response (n=122, n=130, n=94) | 53.3 | 58.5 | 55.3 |
| Day 365 No response (n=122, n=130, n=94) | 8.2 | 18.5 | 13.8 |
| Day 533 Good response (n=118, n=121, n=92) | 38.1 | 33.1 | 35.9 |
| Day 533 Moderate response (n=118, n=121, n=92) | 58.5 | 58.7 | 53.3 |
| Day 533 No response (n=118, n=121, n=92) | 3.4 | 8.3 | 10.9 |
| Day 729 Good response (n=110, n=121, n=93) | 41.8 | 45.5 | 34.4 |
| Day 729 Moderate response (n=110, n=121, n=93) | 53.6 | 47.9 | 51.6 |
| Day 729 No response (n=110, n=121, n=93) | 4.5 | 6.6 | 14.0 |
The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein \[CRP\]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.
| percentage of participants | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Day 197, ACR 20 (n=130, n=133, n=102) | 73.1 | 68.4 | 44.1 |
| Day 197, ACR 50 (n=129, n=134, n=103) | 45.7 | 42.5 | 21.4 |
| Day 197, ACR 70 (n=130, n=133, n=103) | 23.1 | 27.1 | 10.7 |
| Day 365, ACR 20 (n=130, n=136, n=103) | 88.5 | 69.1 | 75.7 |
| Day 365, ACR 50 (n=131, n=136, n=102) | 55.0 | 43.4 | 54.9 |
| Day 365, ACR 70 (n=131, n=136, n=102) | 31.3 | 23.5 | 31.4 |
| Day 533, ACR 20 (n=128, n=128, n=102) | 82.8 | 82.8 | 74.5 |
| Day 533, ACR 50 (n=129, n=128, n=103) | 58.1 | 57.0 | 47.6 |
| Day 533, ACR 70 (n=129, n=127, n=102) | 35.7 | 40.9 | 32.4 |
| Day 729, ACR 20 (n=119, n=127, n=102) | 86.6 | 84.3 | 76.5 |
| Day 729, ACR 50 (n=117, n=127, n=101) | 60.7 | 70.9 | 49.5 |
| Day 729, ACR 70 (n=120, n=127, n=100) | 40.8 | 44.9 | 33.0 |
Major Clinical Response was defined as a continuous ACR 70 for six months.
No measurements were reported for this outcome.
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.
| percentage of participants | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Day 197 (n=131, n=134, n=103) | 70.2 | 68.7 | 42.7 |
| Day 225 (n=132, n=133, n=101) | 75.0 | 72.9 | 52.5 |
| Day 253 (n=130, n=135, n=102) | 71.5 | 65.2 | 57.8 |
| Day 281 (n=131, n=135, n=102) | 73.3 | 71.9 | 52.0 |
| Day 309 (n=131, n=134, n=102) | 71.0 | 70.1 | 62.7 |
| Day 337 (n=130, n=136, n=101) | 71.5 | 72.1 | 63.4 |
| Day 365 (n=130, n=136, n=103) | 70.8 | 67.6 | 61.2 |
| Day 449 (n=129, n=133, n=101) | 70.5 | 72.9 | 64.4 |
| Day 533 (n=128, n=127, n=103) | 74.2 | 78.0 | 61.2 |
| Day 617 (n=123, n=127, n=103) | 78.9 | 79.5 | 64.1 |
| Day 729 (n=122, n=127, n=103) | 74.6 | 78.0 | 63.1 |
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.
| units on a scale | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| HAQ-DI | -0.83 ± 0.06 | -0.84 ± 0.06 | -0.64 ± 0.07 |
| HAQ-DI component: dressing and grooming | -0.93 ± 0.08 | -91.0 ± 0.08 | -0.68 ± 0.09 |
| HAQ-DI component: arising | -0.8 ± 0.09 | -0.77 ± 0.08 | -0.72 ± 0.09 |
| HAQ-DI component: eating | -0.86 ± 0.09 | -0.99 ± 0.09 | -0.82 ± 0.10 |
| HAQ-DI component: walking | -0.78 ± 0.09 | -0.73 ± 0.08 | -0.54 ± 0.08 |
| HAQ-DI component: hygiene | -0.65 ± 0.10 | -0.65 ± 0.08 | -0.5 ± 0.09 |
| HAQ-DI component: reach | -0.97 ± 0.09 | -0.94 ± 0.10 | -0.64 ± 0.09 |
| HAQ-DI component: grip | -0.88 ± 0.09 | -0.96 ± 0.09 | -0.61 ± 0.09 |
| HAQ-DI component: activities | -0.75 ± 0.09 | -0.73 ± 0.09 | -0.61 ± 0.09 |
Leukocytes: \<0.75 x LLN, \>1.25 x ULN; neutrophils+bands: \<1.0 x 10\^3 c/uL; eosinophils: \>0.750 x 10\^3 c/uL; basophils: \> 400 mm3; monocytes: \>2000 mm3; lymphocytes: \<0.750 x 10\^3 c/uL, \>7.50 x 10\^3 c/uL.
| 10^3 c/uL | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Leukocytes (n=124, n=125, n=102) | -1.57 ± 0.23 | -1.23 ± 0.26 | -1.28 ± 0.23 |
| Neutrophils + bands (n=123, n=123, n=101) | -1.62 ± 0.21 | -1.35 ± 0.23 | -1.33 ± 0.22 |
| Basophils (n=123, n=123, n=101) | -0.01 ± 0.00 | 0.00 ± 0.00 | -0.01 ± 0.00 |
| Monocytes (n=123, n=123, n=101) | -0.05 ± 0.02 | -0.02 ± 0.04 | -0.03 ± 0.02 |
| Eosinophils (n=123, n=123, n=101) | -0.01 ± 0.01 | -0.03 ± 0.02 | -0.05 ± 0.02 |
| Lymphocytes (n=123, n=123, n=101) | 0.13 ± 0.06 | 0.18 ± 0.06 | 0.08 ± 0.06 |
Erythrocytes: \<0.75 x BL
| 10^6 c/uL | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| OL; Mean Change From Baseline to Day 729 in Erythrocytes | 0.07 ± 0.03 | 0.04 ± 0.03 | 0.02 ± 0.04 |
Sodium (Na): \<0.95 x LLN, \>1.05 x ULN; potassium (K): \<0.9 x LLN, \>1.1 x ULN; chloride (Cl): \<0.9 x LLN, \>1.1 x ULN
| mEq/L | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Na | -1.10 ± 0.28 | -1.12 ± 0.29 | -1.22 ± 0.38 |
| K | -0.03 ± 0.04 | -0.04 ± 0.04 | -0.02 ± 0.04 |
| Cl | -1.31 ± 0.26 | -1.28 ± 0.31 | -2.03 ± 0.29 |
Bilirubin: \>2 x ULN; blood urea nitrogen (BUN): \>2 x BL; creatinine: \>4 x BL; calcium (Ca): \<0.8 x LLN, \>1.2 x ULN; phosphorous (P): \<0.75 x LLN, \>1.2 5 x ULN; serum glucose (Glu): \<65 mg/dL, \>220 mg/dL; fasting serum Glu: \<0.8 x LLN, \>1.5 x ULN; uric acid: \>1.5 x ULN;
| mg/dL | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Creatinine (n=124, n=127, n=102) | 0.08 ± 0.02 | 0.08 ± 0.01 | 0.07 ± 0.02 |
| BUN (n=124, n=127, n=102) | -0.37 ± 0.43 | -0.12 ± 0.44 | 0.20 ± 0.46 |
| Ca (n=124, n=127, n=102) | 0.01 ± 0.04 | -0.01 ± 0.05 | 0.02 ± 0.05 |
| P (n=124, n=127, n=102) | -0.05 ± 0.05 | -0.16 ± 0.06 | -0.08 ± 0.06 |
| Uric Acid (n=124, n=127, n=102) | -0.22 ± 0.08 | -0.02 ± 0.09 | -0.10 ± 0.12 |
| Total bilirubin (n=124, n=127, n=101) | 0.01 ± 0.02 | 0.04 ± 0.02 | 0.03 ± 0.02 |
| Serum glucose (n=123, n=126, n=101) | 9.92 ± 3.04 | 7.52 ± 2.02 | 3.74 ± 2.17 |
alanine aminotransferase (ALT): \>3 x ULN; aspartate aminotransferase (AST): \>3 x ULN; G-Glutamyl transferase (GGT): \>2 x ULN; Alkaline phosphatase (ALP): \>2 x ULN
| U/L | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| ALT | 2.73 ± 1.59 | 1.02 ± 1.83 | -0.89 ± 1.96 |
| AST | 0.03 ± 1.17 | -0.22 ± 1.22 | -2.45 ± 1.60 |
| GGT | 1.23 ± 2.38 | -0.41 ± 2.14 | -1.93 ± 2.95 |
| ALP | -0.55 ± 2.17 | -2.61 ± 2.83 | -3.91 ± 3.41 |
Hemoglobin (HGB): \>3 g/dL decrease from BL; total protein: \< 0.9 x LLN, \>1.1 x ULN; albumin:\<0.9 x LLN
| g/dL | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| HGB (n=102, n=98, n=85) | 0.66 ± 0.13 | 0.53 ± 0.14 | 0.57 ± 0.13 |
| Total protein (n=102, n=98, n=86) | -0.35 ± 0.05 | -0.24 ± 0.05 | -0.33 ± 0.05 |
| Albumin (n=102, n=98, n=86) | 0.04 ± 0.04 | 0.08 ± 0.04 | -0.01 ± 0.04 |
Platelets (PLT): \<0.67 x LLN, \>1.5 x ULN
| 10^9 c/L | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| OL; Mean Change From Baseline to Day 1121 in Platelets | -67.5 ± 7.49 | -66.1 ± 8.86 | -62.5 ± 8.05 |
Hematocrit: \<0.75 x BL
| percentage of red blood cells | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| OL; Mean Change From Baseline to Day 1121 in Hematocrit | 1.83 ± 0.37 | 1.50 ± 0.39 | 1.47 ± 0.39 |
Leukocytes: \<0.75 x LLN, \>1.25 x ULN; neutrophils+bands: \<1.0 x 10\^3 c/uL; eosinophils: \>0.750 x 10\^3 c/uL; basophils: \> 400 mm3; monocytes: \>2000 mm3; lymphocytes: \<0.750 x 10\^3 c/uL, \>7.50 x 10\^3 c/uL.
| 10^3 c/uL | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Leukocytes (n=102, n=98, n=85) | -1.07 ± 0.27 | -1.09 ± 0.26 | -0.99 ± 0.25 |
| Neutrophils + bands (n=99, n=96, n=84) | -1.17 ± 0.25 | -1.40 ± 0.25 | -1.28 ± 0.24 |
| Basophils (n=99, n=96, n=85) | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 |
| Monocytes (n=99, n=96, n=84) | 0.03 ± 0.02 | 0.00 ± 0.03 | 0.01 ± 0.03 |
| Eosinophils (n=99, n=96, n=84) | 0.00 ± 0.01 | -0.06 ± 0.02 | -0.04 ± 0.02 |
| Lymphocytes (n=99, n=96, n=84) | 0.16 ± 0.08 | 0.34 ± 0.07 | 0.32 ± 0.10 |
Erythrocytes: \<0.75 x BL
| 10^6 c/uL | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| OL; Mean Change From Baseline to Day 1121 in Erythrocytes | 0.11 ± 0.03 | 0.11 ± 0.04 | 0.12 ± 0.04 |
Sodium (Na): \<0.95 x LLN, \>1.05 x ULN; potassium (K): \<0.9 x LLN, \>1.1 x ULN; chloride (Cl): \<0.9 x LLN, \>1.1 x ULN
| mEq/L | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Na (n=102, n=98, n=86) | -1.80 ± 0.33 | -1.38 ± 0.38 | -1.34 ± 0.42 |
| K (n=102, n=98, n=85) | 0.01 ± 0.04 | 0.08 ± 0.05 | 0.01 ± 0.05 |
| Cl (n=102, n=98, n=86) | -0.88 ± 0.35 | -0.94 ± 0.38 | -1.42 ± 0.37 |
Bilirubin: \>2 x ULN; blood urea nitrogen (BUN): \>2 x BL; creatinine: \>4 x BL; calcium (Ca): \<0.8 x LLN, \>1.2 x ULN; phosphorous (P): \<0.75 x LLN, \>1.2 5 x ULN; serum glucose (Glu): \<65 mg/dL, \>220 mg/dL; fasting serum Glu: \<0.8 x LLN, \>1.5 x ULN; uric acid: \>1.5 x ULN;
| mg/dL | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Creatinine (n=102, n=98, n=86) | 0.06 ± 0.02 | 0.07 ± 0.03 | 0.08 ± 0.02 |
| BUN (n=102, n=98, n=86) | -0.04 ± 0.49 | 0.34 ± 0.73 | 0.20 ± 0.56 |
| Ca (n=102, n=98, n=86) | -0.01 ± 0.05 | -0.03 ± 0.06 | 0.04 ± 0.05 |
| P (n=102, n=98, n=85) | -0.18 ± 0.07 | -0.19 ± 0.07 | -0.11 ± 0.06 |
| Uric Acid (n=102, n=98, n=86) | -0.05 ± 0.11 | 0.13 ± 0.10 | 0.20 ± 0.15 |
| Total bilirubin (n=102, n=98, n=86) | 0.02 ± 0.02 | 0.03 ± 0.02 | 0.03 ± 0.02 |
| Serum glucose (n=101, n=98, n=85) | 12.99 ± 3.31 | 6.91 ± 2.10 | 9.07 ± 3.20 |
alanine aminotransferase (ALT): \>3 x ULN; aspartate aminotransferase (AST): \>3 x ULN; G-Glutamyl transferase (GGT): \>2 x ULN; Alkaline phosphatase (ALP): \>2 x ULN
| U/L | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| ALT (n=102, n=98, n=86) | 4.74 ± 1.95 | 4.66 ± 2.88 | -0.35 ± 2.33 |
| AST (n=102, n=98, n=86) | 3.79 ± 1.60 | 4.49 ± 2.13 | 0.38 ± 1.69 |
| GGT (n=102, n=98, n=86) | 1.60 ± 2.79 | -2.88 ± 2.16 | -0.14 ± 3.79 |
| ALP (n=88, n=79, n=69) | 1.25 ± 2.62 | -4.03 ± 3.79 | -7.35 ± 3.53 |
Hemoglobin (HGB): \>3 g/dL decrease from BL; total protein: \< 0.9 x LLN, \>1.1 x ULN; albumin:\<0.9 x LLN
| g/dL | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| HGB | 0.25 ± 0.33 | 0.44 ± 0.31 | 0.56 ± 0.32 |
| Total protein | -0.73 ± 0.09 | -0.33 ± 0.11 | -0.34 ± 0.14 |
| Albumin | -0.06 ± 0.07 | 0.10 ± 0.07 | 0.00 ± 0.11 |
Platelets (PLT): \<0.67 x LLN, \>1.5 x ULN
| 10^9 c/L | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| OL; Mean Change From Baseline to Day 1513 in Platelets | -78.0 ± 17.20 | -74.0 ± 16.18 | -99.2 ± 19.83 |
Hematocrit: \<0.75 x BL
| percentage of red blood cells | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| OL; Mean Change From Baseline to Day 1513 in Hematocrit | 0.92 ± 1.00 | 1.28 ± 0.92 | 1.18 ± 1.00 |
Leukocytes: \<0.75 x LLN, \>1.25 x ULN; neutrophils+bands: \<1.0 x 10\^3 c/uL; eosinophils: \>0.750 x 10\^3 c/uL; basophils: \> 400 mm3; monocytes: \>2000 mm3; lymphocytes: \<0.750 x 10\^3 c/uL, \>7.50 x 10\^3 c/uL.
| 10^3 c/uL | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Leukocytes (n=23, n=20, n=16) | -0.34 ± 0.45 | -1.08 ± 0.63 | -2.13 ± 0.50 |
| Neutrophils + bands (n=22, n=17, n=16) | -0.37 ± 0.33 | -1.03 ± 0.68 | -1.93 ± 0.50 |
| Basophils (n=22, n=17, n=16) | 0.00 ± 0.01 | -0.01 ± 0.01 | -0.01 ± 0.01 |
| Monocytes (n=22, n=17, n=16) | 0.01 ± 0.03 | -0.10 ± 0.09 | -0.05 ± 0.04 |
| Eosinophils (n=22, n=17, n=16) | 0.04 ± 0.06 | -0.11 ± 0.16 | -0.23 ± 0.00 |
| Lymphocytes (n=22, n=17, n=16) | 0.20 ± 0.14 | 0.16 ± 0.16 | -0.15 ± 0.16 |
Erythrocytes: \<0.75 x BL
| 10^6 c/uL | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| OL; Mean Change From Baseline to Day 1513 in Erythrocytes | -0.10 ± 0.09 | 0.00 ± 0.09 | -0.09 ± 0.08 |
Sodium (Na): \<0.95 x LLN, \>1.05 x ULN; potassium (K): \<0.9 x LLN, \>1.1 x ULN; chloride (Cl): \<0.9 x LLN, \>1.1 x ULN
| mEq/L | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Na (n=22, n=20, n=16) | -4.36 ± 0.73 | -3.80 ± 0.99 | -4.50 ± 0.74 |
| K (n=23, n=20, n=16) | -0.16 ± 0.10 | -0.32 ± 0.08 | -0.46 ± 0.11 |
| Cl (n=23, n=20, n=16) | -2.48 ± 0.71 | -2.60 ± 0.84 | -4.13 ± 0.88 |
Bilirubin: \>2 x ULN; blood urea nitrogen (BUN): \>2 x BL; creatinine: \>4 x BL; calcium (Ca): \<0.8 x LLN, \>1.2 x ULN; phosphorous (P): \<0.75 x LLN, \>1.2 5 x ULN; serum glucose (Glu): \<65 mg/dL, \>220 mg/dL; fasting serum Glu: \<0.8 x LLN, \>1.5 x ULN; uric acid: \>1.5 x ULN;
| mg/dL | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| Creatinine | 0.10 ± 0.02 | 0.05 ± 0.04 | 0.08 ± 0.06 |
| BUN | 2.87 ± 0.90 | -0.40 ± 1.13 | 0.63 ± 1.36 |
| Ca | 0.27 ± 0.07 | 0.38 ± 0.09 | 0.35 ± 0.12 |
| P | -0.09 ± 0.11 | -0.51 ± 0.16 | -0.17 ± 0.13 |
| Uric Acid | 0.03 ± 0.18 | 0.06 ± 0.21 | 0.33 ± 0.33 |
| Total bilirubin | 0.08 ± 0.10 | 0.09 ± 0.03 | 0.23 ± 0.14 |
| Serum glucose | 8.87 ± 3.19 | 9.00 ± 1.88 | 8.44 ± 4.38 |
alanine aminotransferase (ALT): \>3 x ULN; aspartate aminotransferase (AST): \>3 x ULN; G-Glutamyl transferase (GGT): \>2 x ULN; Alkaline phosphatase (ALP): \>2 x ULN
| U/L | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|
| ALT | -1.87 ± 2.73 | -9.20 ± 3.75 | 2.44 ± 8.07 |
| AST | -1.35 ± 1.72 | -2.85 ± 2.55 | 0.38 ± 7.23 |
| GGT | -3.00 ± 2.99 | -10.9 ± 5.79 | -3.06 ± 10.30 |
| ALP | -15.8 ± 5.23 | -18.7 ± 7.12 | -11.30 ± 7.80 |
Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP), units=mm mercury (Hg)
| mm mercury (Hg) | ABA + MTX [OL] |
|---|---|
| Day 365 SBP pre-dose (n=343) | 119.0 ± 15.03 |
| Day 365 SBP post-dose (n=341) | 118.8 ± 15.35 |
| Day 729 SBP pre-dose (n=321) | 120.4 ± 15.20 |
| Day 729 SBP post-dose (n=323) | 119.5 ± 15.02 |
| Day 1121 SBP pre-dose (n=265) | 121.1 ± 15.59 |
| Day 1121 SBP post-dose (n=265) | 119.2 ± 13.99 |
| Day 1513 SBP pre-dose (n=52) | 114.6 ± 13.57 |
| Day 1513 SBP post-dose (n=52) | 114.2 ± 12.90 |
| Day 365 DBP pre-dose (n=343) | 74.5 ± 9.80 |
| Day 365 DBP post-dose (n=341) | 74.0 ± 10.18 |
| Day 729 DBP pre-dose (n=321) | 74.9 ± 9.69 |
| Day 729 DBP post-dose (n=323) | 74.6 ± 9.92 |
| Day 1121 DBP pre-dose (n=265) | 74.9 ± 9.45 |
| Day 1121 DBP post-dose (n=265) | 73.6 ± 9.12 |
| Day 1513 DBP pre-dose (n=52) | 71.7 ± 9.45 |
| Day 1513 DBP post-dose (n=52) | 72.1 ± 9.11 |
Heart Rate (HR), units=beats per minute (bpm)
| beats per minute (bpm) | ABA + MTX [OL] |
|---|---|
| Day 365 HR pre-dose (n=343) | 74.2 ± 9.30 |
| Day 365 HR post-dose (n=341) | 74.1 ± 8.57 |
| Day 729 HR pre-dose (n=322) | 74.2 ± 9.12 |
| Day 729 HR post-dose (n=324) | 73.4 ± 8.59 |
| Day 1121 HR pre-dose (n=265) | 73.9 ± 9.31 |
| Day 1121 HR post-dose (n=265) | 73.8 ± 9.46 |
| Day 1513 HR pre-dose (n=52) | 73.0 ± 8.38 |
| Day 1513 HR post-dose (n=52) | 73.8 ± 7.16 |
Temperature (T), units=degrees Celcius
| degrees Celsius | ABA + MTX [OL] |
|---|---|
| Day 365 T pre-dose (n=339) | 36.3 ± 0.43 |
| Day 365 T post-dose (n=339) | 36.3 ± 0.41 |
| Day 729 T pre-dose (n=320) | 36.3 ± 0.45 |
| Day 729 T post-dose (n=323) | 36.3 ± 0.42 |
| Day 1121 T pre-dose (n=263) | 36.2 ± 0.51 |
| Day 1121 T post-dose (n=264) | 36.2 ± 0.47 |
| Day 1513 T pre-dose (n=52) | 36.1 ± 0.35 |
| Day 1513 T post-dose (n=52) | 36.1 ± 0.37 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| ABA (DB) | — | 17/156 (10.9%) | 105/156 (67.3%) |
| ABA + MTX [OL] | — | 90/372 (24.2%) | 285/372 (76.6%) |
| INF + MTX [DB] | — | 30/165 (18.2%) | 130/165 (78.8%) |
| PLA + MTX [DB] | — | 21/110 (19.1%) | 82/110 (74.5%) |
| Event | ABA (DB) | ABA + MTX [OL] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|---|
| RHEUMATOID ARTHRITISMusculoskeletal and connective tissue disorders | 1/156 | 19/372 | 4/165 | 4/110 |
| PNEUMONIAInfections and infestations | 2/156 | 1/372 | 3/165 | 1/110 |
| OSTEOARTHRITISMusculoskeletal and connective tissue disorders | 1/156 | 4/372 | 0/165 | 2/110 |
| URINARY TRACT INFECTIONInfections and infestations | 0/156 | 5/372 | 0/165 | 0/110 |
| ARTHRITISMusculoskeletal and connective tissue disorders | 0/156 | 4/372 | 0/165 | 0/110 |
| ALANINE AMINOTRANSFERASE INCREASEDInvestigations | 0/156 | 0/372 | 0/165 | 1/110 |
| ASPARTATE AMINOTRANSFERASE INCREASEDInvestigations | 0/156 | 0/372 | 0/165 | 1/110 |
| PERICARDITISCardiac disorders | 0/156 | 0/372 | 0/165 | 1/110 |
| ANAPHYLACTIC SHOCKImmune system disorders | 0/156 | 0/372 | 0/165 | 1/110 |
| SCIATICANervous system disorders | 0/156 | 0/372 | 0/165 | 1/110 |
| Event | ABA (DB) | ABA + MTX [OL] | INF + MTX [DB] | PLA + MTX [DB] |
|---|---|---|---|---|
| HEADACHENervous system disorders | 23/156 | 54/372 | 34/165 | 24/110 |
| NASOPHARYNGITISInfections and infestations | 20/156 | 69/372 | 26/165 | 15/110 |
| URINARY TRACT INFECTIONInfections and infestations | 8/156 | 67/372 | 18/165 | 13/110 |
| DIARRHOEAGastrointestinal disorders | 21/156 | 56/372 | 21/165 | 7/110 |
| UPPER RESPIRATORY TRACT INFECTIONInfections and infestations | 11/156 | 50/372 | 19/165 | 16/110 |
| INFLUENZAInfections and infestations | 13/156 | 49/372 | 12/165 | 6/110 |
| NAUSEAGastrointestinal disorders | 16/156 | 26/372 | 21/165 | 10/110 |
| DYSPEPSIAGastrointestinal disorders | 19/156 | 41/372 | 17/165 | 7/110 |
| HYPERTENSIONVascular disorders | 13/156 | 42/372 | 11/165 | 13/110 |
| PHARYNGITISInfections and infestations | 12/156 | 43/372 | 17/165 | 9/110 |
| Age, Continuous(years) | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] | Total |
|---|---|---|---|---|
| Mean | 49.0 ± 12.5 | 49.1 ± 12.0 | 49.4 ± 11.5 | 49.1 ± 12.0 |
| Sex: Female, Male(Participants) | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] | Total |
|---|---|---|---|---|
| Female | 130 | 136 | 96 | 362 |
| Male | 26 | 29 | 14 | 69 |
| Baseline Disease Activity Score (DAS) 28 (Erythrocyte Sedimentation Rate [ESR])(units on a scale) | ABA + MTX [DB] | INF + MTX [DB] | PLA + MTX [DB] | Total |
|---|---|---|---|---|
| Mean | 6.9 ± 1.0 | 6.8 ± 0.9 | 6.8 ± 1.0 | 6.8 ± 1.0 |
This study is completed, as verified in Mar 2015. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Bristol-Myers Squibb