Trial Outcomes & Findings for Abatacept and Infliximab in Combination With Methotrexate in Subjects With Rheumatoid Arthritis (NCT NCT00095147)
NCT ID: NCT00095147
Last Updated: 2015-03-24
Results Overview
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.
COMPLETED
PHASE3
431 participants
Baseline (Day 1), 6 months (Day 197)
2015-03-24
Participant Flow
748 participants enrolled in this study; 317 participants were not randomized or treated. 384 participants completed the double-blind period; 12 participants did not enter the open-label period.
Participant milestones
| Measure |
Abatacept (ABA) + Methotrexate (MTX) [Double-blind (DB)]
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
Infliximab (INF) + MTX [DB]
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
Placebo (PLA) + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA Switched to ABA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
|
ABA + MTX [Open-label (OL)]
All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
|
|---|---|---|---|---|---|
|
Double-blind Period 1 (Days 1-197)
STARTED
|
156
|
165
|
110
|
0
|
0
|
|
Double-blind Period 1 (Days 1-197)
COMPLETED
|
147
|
152
|
107
|
0
|
0
|
|
Double-blind Period 1 (Days 1-197)
NOT COMPLETED
|
9
|
13
|
3
|
0
|
0
|
|
Double-blind Period 2 (Days 198-365)
STARTED
|
147
|
152
|
0
|
107
|
0
|
|
Double-blind Period 2 (Days 198-365)
COMPLETED
|
139
|
141
|
0
|
104
|
0
|
|
Double-blind Period 2 (Days 198-365)
NOT COMPLETED
|
8
|
11
|
0
|
3
|
0
|
|
Long-term Extension Period
STARTED
|
0
|
0
|
0
|
0
|
372
|
|
Long-term Extension Period
COMPLETED
|
0
|
0
|
0
|
0
|
327
|
|
Long-term Extension Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
45
|
Reasons for withdrawal
| Measure |
Abatacept (ABA) + Methotrexate (MTX) [Double-blind (DB)]
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
Infliximab (INF) + MTX [DB]
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
Placebo (PLA) + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA Switched to ABA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
|
ABA + MTX [Open-label (OL)]
All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
|
|---|---|---|---|---|---|
|
Double-blind Period 1 (Days 1-197)
Death
|
1
|
0
|
0
|
0
|
0
|
|
Double-blind Period 1 (Days 1-197)
Adverse Event
|
2
|
8
|
1
|
0
|
0
|
|
Double-blind Period 1 (Days 1-197)
Lack of Efficacy
|
2
|
2
|
1
|
0
|
0
|
|
Double-blind Period 1 (Days 1-197)
Lost to Follow-up
|
2
|
2
|
0
|
0
|
0
|
|
Double-blind Period 1 (Days 1-197)
Withdrawal of consent
|
1
|
0
|
1
|
0
|
0
|
|
Double-blind Period 1 (Days 1-197)
Pregnancy
|
1
|
1
|
0
|
0
|
0
|
|
Double-blind Period 2 (Days 198-365)
Death
|
0
|
1
|
0
|
1
|
0
|
|
Double-blind Period 2 (Days 198-365)
Adverse Event
|
2
|
4
|
0
|
0
|
0
|
|
Double-blind Period 2 (Days 198-365)
Lack of Efficacy
|
2
|
4
|
0
|
1
|
0
|
|
Double-blind Period 2 (Days 198-365)
Withdrawal of consent
|
3
|
2
|
0
|
0
|
0
|
|
Double-blind Period 2 (Days 198-365)
Participant relocation
|
1
|
0
|
0
|
1
|
0
|
|
Long-term Extension Period
Death
|
0
|
0
|
0
|
0
|
3
|
|
Long-term Extension Period
Adverse Event
|
0
|
0
|
0
|
0
|
11
|
|
Long-term Extension Period
Lack of Efficacy
|
0
|
0
|
0
|
0
|
9
|
|
Long-term Extension Period
Lost to Follow-up
|
0
|
0
|
0
|
0
|
6
|
|
Long-term Extension Period
Withdrawal of consent
|
0
|
0
|
0
|
0
|
12
|
|
Long-term Extension Period
Pregnancy
|
0
|
0
|
0
|
0
|
1
|
|
Long-term Extension Period
No longer meets study criteria
|
0
|
0
|
0
|
0
|
1
|
|
Long-term Extension Period
Participant chose to use Revellex
|
0
|
0
|
0
|
0
|
1
|
|
Long-term Extension Period
Leaving country
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Abatacept and Infliximab in Combination With Methotrexate in Subjects With Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
ABA + MTX [DB]
n=156 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
INF + MTX [DB]
n=165 Participants
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=110 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
Total
n=431 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
49.0 years
STANDARD_DEVIATION 12.5 • n=5 Participants
|
49.1 years
STANDARD_DEVIATION 12.0 • n=7 Participants
|
49.4 years
STANDARD_DEVIATION 11.5 • n=5 Participants
|
49.1 years
STANDARD_DEVIATION 12.0 • n=4 Participants
|
|
Sex: Female, Male
Female
|
130 Participants
n=5 Participants
|
136 Participants
n=7 Participants
|
96 Participants
n=5 Participants
|
362 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
69 Participants
n=4 Participants
|
|
Baseline Disease Activity Score (DAS) 28 (Erythrocyte Sedimentation Rate [ESR])
|
6.9 units on a scale
STANDARD_DEVIATION 1.0 • n=5 Participants
|
6.8 units on a scale
STANDARD_DEVIATION 0.9 • n=7 Participants
|
6.8 units on a scale
STANDARD_DEVIATION 1.0 • n=5 Participants
|
6.8 units on a scale
STANDARD_DEVIATION 1.0 • n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day 1), 6 months (Day 197)Population: The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=150 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=102 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
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 units on a scale
Standard Error 0.12
|
-1.48 units on a scale
Standard Error 0.15
|
—
|
PRIMARY outcome
Timeframe: From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)Population: All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=372 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
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
Deaths
|
3 participants
|
—
|
—
|
|
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
SAEs
|
90 participants
|
—
|
—
|
|
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
Related SAEs
|
12 participants
|
—
|
—
|
|
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
SAEs Leading to Discontinuation
|
5 participants
|
—
|
—
|
|
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
AEs
|
349 participants
|
—
|
—
|
|
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
Related AEs
|
165 participants
|
—
|
—
|
|
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
AEs Leading to discontinuation
|
10 participants
|
—
|
—
|
PRIMARY outcome
Timeframe: From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)Population: All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.
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).
Outcome measures
| Measure |
ABA + MTX [DB]
n=372 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Number of Participants With AEs of Special Interest
Infections
|
277 participants
|
—
|
—
|
|
OL; Number of Participants With AEs of Special Interest
Malignant neoplasms
|
3 participants
|
—
|
—
|
|
OL; Number of Participants With AEs of Special Interest
Benign and unspecified neoplasms
|
18 participants
|
—
|
—
|
|
OL; Number of Participants With AEs of Special Interest
Prespecified autoimmune symptoms and disorders
|
13 participants
|
—
|
—
|
|
OL; Number of Participants With AEs of Special Interest
Pre-specified peri-infusional AEs
|
50 participants
|
—
|
—
|
|
OL; Number of Participants With AEs of Special Interest
Pre-specified acute infusional AEs
|
28 participants
|
—
|
—
|
PRIMARY outcome
Timeframe: From Day 366 through end of OL (range from 1.9 months to 42.3 months)Population: All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.
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;
Outcome measures
| Measure |
ABA + MTX [DB]
n=372 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Number of Participants With Select Hematologic Laboratory Abnormalities
Low HGB (>3g/dL decrease from BL), n=372
|
9 participants
|
—
|
—
|
|
OL; Number of Participants With Select Hematologic Laboratory Abnormalities
Low hematocrit (< 0.75 x BL), n=372
|
7 participants
|
—
|
—
|
|
OL; Number of Participants With Select Hematologic Laboratory Abnormalities
Low erythrocytes (<0.75 x BL), n=372
|
6 participants
|
—
|
—
|
|
OL; Number of Participants With Select Hematologic Laboratory Abnormalities
Low PLT (<0.67 x LLN), n=370
|
2 participants
|
—
|
—
|
|
OL; Number of Participants With Select Hematologic Laboratory Abnormalities
High leukocytes (>1.25 x ULN), n=372
|
29 participants
|
—
|
—
|
|
OL; Number of Participants With Select Hematologic Laboratory Abnormalities
Low neutrophils + bands (<1.0 x 10^3 c/uL), n=372
|
1 participants
|
—
|
—
|
|
OL; Number of Participants With Select Hematologic Laboratory Abnormalities
Low lymphocytes (<0.75 x 10^3 c/uL), n=372
|
12 participants
|
—
|
—
|
|
OL; Number of Participants With Select Hematologic Laboratory Abnormalities
High monocytes (>2000/mm^3), n=372
|
3 participants
|
—
|
—
|
|
OL; Number of Participants With Select Hematologic Laboratory Abnormalities
High eosinophils (>0.750 x 10^3 c/uL), n=372
|
15 participants
|
—
|
—
|
PRIMARY outcome
Timeframe: From Day 366 through end of OL (range from 1.9 months to 42.3 months)Population: All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.
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
Outcome measures
| Measure |
ABA + MTX [DB]
n=371 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Number of Participants With Select Blood Chemistry Laboratory Abnormalities
High ALP (>2 x ULN)
|
1 participants
|
—
|
—
|
|
OL; Number of Participants With Select Blood Chemistry Laboratory Abnormalities
High AST (>3 x ULN)
|
4 participants
|
—
|
—
|
|
OL; Number of Participants With Select Blood Chemistry Laboratory Abnormalities
High ALT (>3 x ULN)
|
11 participants
|
—
|
—
|
|
OL; Number of Participants With Select Blood Chemistry Laboratory Abnormalities
High GGT (>2 x ULN)
|
16 participants
|
—
|
—
|
|
OL; Number of Participants With Select Blood Chemistry Laboratory Abnormalities
High total bilirubin (>2 x ULN)
|
1 participants
|
—
|
—
|
|
OL; Number of Participants With Select Blood Chemistry Laboratory Abnormalities
High BUN (>2 x BL)
|
17 participants
|
—
|
—
|
|
OL; Number of Participants With Select Blood Chemistry Laboratory Abnormalities
High creatinine (>1.5 increase from BL)
|
44 participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 365Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Hemoglobin (HGB): \>3 g/dL decrease from BL; total protein: \< 0.9 x LLN, \>1.1 x ULN; albumin:\<0.9 x LLN
Outcome measures
| Measure |
ABA + MTX [DB]
n=131 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=136 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=104 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 365 in Hemoglobin, Total Protein, and Albumin
HGB (n=131, n=135, n=103)
|
0.53 g/dL
Standard Error 0.09
|
0.24 g/dL
Standard Error 0.09
|
0.43 g/dL
Standard Error 0.09
|
|
OL; Mean Change From Baseline to Day 365 in Hemoglobin, Total Protein, and Albumin
Total protein (n=131, n=136, n=104)
|
-0.09 g/dL
Standard Error 0.04
|
0.11 g/dL
Standard Error 0.04
|
-0.12 g/dL
Standard Error 0.04
|
|
OL; Mean Change From Baseline to Day 365 in Hemoglobin, Total Protein, and Albumin
Albumin (n=131, n=136, n=104)
|
0.12 g/dL
Standard Error 0.03
|
0.00 g/dL
Standard Error 0.03
|
0.05 g/dL
Standard Error 0.03
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 365Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Platelets (PLT): \<0.67 x LLN, \>1.5 x ULN
Outcome measures
| Measure |
ABA + MTX [DB]
n=129 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=129 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=102 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 365 in Platelets
|
-42.4 10^9 c/L
Standard Error 5.20
|
-35.5 10^9 c/L
Standard Error 6.93
|
-28.4 10^9 c/L
Standard Error 6.75
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 365Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Hematocrit: \<0.75 x BL
Outcome measures
| Measure |
ABA + MTX [DB]
n=129 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=134 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=102 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 365 in Hematocrit
|
1.44 percentage red blood cells
Standard Error 0.29
|
0.51 percentage red blood cells
Standard Error 0.27
|
1.03 percentage red blood cells
Standard Error 0.27
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 365Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=131 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=134 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=104 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 365 in White Blood Cells
Leukocytes (n=131, n=134, n=103)
|
-0.95 10^3 c/uL
Standard Error 0.23
|
-0.90 10^3 c/uL
Standard Error 0.21
|
-0.84 10^3 c/uL
Standard Error 0.23
|
|
OL; Mean Change From Baseline to Day 365 in White Blood Cells
Neutrophils + bands (n=130, n=130, n=104)
|
-0.91 10^3 c/uL
Standard Error 0.20
|
-1.14 10^3 c/uL
Standard Error 0.20
|
-1.05 10^3 c/uL
Standard Error 0.22
|
|
OL; Mean Change From Baseline to Day 365 in White Blood Cells
Basophils (n=130, n=130, n=101)
|
-0.01 10^3 c/uL
Standard Error 0.00
|
0.00 10^3 c/uL
Standard Error 0.00
|
0.00 10^3 c/uL
Standard Error 0.00
|
|
OL; Mean Change From Baseline to Day 365 in White Blood Cells
Monocytes (n=130, n=130, n=101)
|
-0.01 10^3 c/uL
Standard Error 0.02
|
-0.01 10^3 c/uL
Standard Error 0.02
|
0.02 10^3 c/uL
Standard Error 0.02
|
|
OL; Mean Change From Baseline to Day 365 in White Blood Cells
Eosinophils (n=130, n=130, n=101)
|
-0.04 10^3 c/uL
Standard Error 0.01
|
-0.02 10^3 c/uL
Standard Error 0.02
|
-0.03 10^3 c/uL
Standard Error 0.01
|
|
OL; Mean Change From Baseline to Day 365 in White Blood Cells
Lymphocytes (n=130, n=130, n=101)
|
0.03 10^3 c/uL
Standard Error 0.07
|
0.24 10^3 c/uL
Standard Error 0.06
|
0.22 10^3 c/uL
Standard Error 0.08
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 365Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Erythrocytes: \<0.75 x BL
Outcome measures
| Measure |
ABA + MTX [DB]
n=131 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=135 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=103 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 365 in Erythrocytes
|
0.09 10^6 c/uL
Standard Error 0.03
|
0.00 10^6 c/uL
Standard Error 0.03
|
0.006 10^6 c/uL
Standard Error 0.03
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 365Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
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
Outcome measures
| Measure |
ABA + MTX [DB]
n=131 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=136 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=104 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 365 in Electrolytes
Na (n=131, n=136, n=104)
|
-1.62 mEq/L
Standard Error 0.29
|
-1.57 mEq/L
Standard Error 0.33
|
-1.09 mEq/L
Standard Error 0.38
|
|
OL; Mean Change From Baseline to Day 365 in Electrolytes
K (n=131, n=135, n=104)
|
-0.03 mEq/L
Standard Error 0.04
|
-0.07 mEq/L
Standard Error 0.04
|
-0.03 mEq/L
Standard Error 0.05
|
|
OL; Mean Change From Baseline to Day 365 in Electrolytes
Cl (n=131, n=136, n=104)
|
-1.40 mEq/L
Standard Error 0.28
|
-1.18 mEq/L
Standard Error 0.31
|
-1.06 mEq/L
Standard Error 0.33
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 365Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
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;
Outcome measures
| Measure |
ABA + MTX [DB]
n=131 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=136 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=104 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 365 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Creatinine (n=131, n=136, n=104)
|
0.03 mg/dL
Standard Error 0.02
|
0.02 mg/dL
Standard Error 0.01
|
0.01 mg/dL
Standard Error 0.02
|
|
OL; Mean Change From Baseline to Day 365 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
BUN (n=131, n=136, n=104)
|
-0.31 mg/dL
Standard Error 0.41
|
-0.52 mg/dL
Standard Error 0.40
|
0.10 mg/dL
Standard Error 0.53
|
|
OL; Mean Change From Baseline to Day 365 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Ca (n=131, n=136, n=104)
|
0.14 mg/dL
Standard Error 0.04
|
0.08 mg/dL
Standard Error 0.03
|
0.14 mg/dL
Standard Error 0.04
|
|
OL; Mean Change From Baseline to Day 365 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
P (n=131, n=136, n=104)
|
0.03 mg/dL
Standard Error 0.05
|
-0.01 mg/dL
Standard Error 0.05
|
0.05 mg/dL
Standard Error 0.05
|
|
OL; Mean Change From Baseline to Day 365 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Uric Acid (n=131, n=136, n=104)
|
0.09 mg/dL
Standard Error 0.08
|
0.08 mg/dL
Standard Error 0.10
|
0.04 mg/dL
Standard Error 0.12
|
|
OL; Mean Change From Baseline to Day 365 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Total bilirubin (n=131, n=134, n=104)
|
0.06 mg/dL
Standard Error 0.01
|
0.04 mg/dL
Standard Error 0.02
|
0.03 mg/dL
Standard Error 0.02
|
|
OL; Mean Change From Baseline to Day 365 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Serum glucose (n=131, n=136, n=104)
|
5.66 mg/dL
Standard Error 2.41
|
2.49 mg/dL
Standard Error 3.15
|
3.03 mg/dL
Standard Error 2.16
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 365Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
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
Outcome measures
| Measure |
ABA + MTX [DB]
n=131 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=136 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=104 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 365 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
ALT (n=131, n=135, n=104)
|
3.51 U/L
Standard Error 1.33
|
2.19 U/L
Standard Error 2.31
|
-0.04 U/L
Standard Error 1.68
|
|
OL; Mean Change From Baseline to Day 365 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
AST (n=131, n=135, n=104)
|
0.54 U/L
Standard Error 1.04
|
-0.11 U/L
Standard Error 1.51
|
-2.23 U/L
Standard Error 1.41
|
|
OL; Mean Change From Baseline to Day 365 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
GGT (n=131, n=135, n=104)
|
2.53 U/L
Standard Error 2.81
|
-0.61 U/L
Standard Error 1.76
|
-2.32 U/L
Standard Error 2.73
|
|
OL; Mean Change From Baseline to Day 365 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
ALP (n=131, n=136, n=104)
|
-0.53 U/L
Standard Error 2.16
|
-7.78 U/L
Standard Error 2.24
|
-4.34 U/L
Standard Error 2.48
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 729Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Hemoglobin (HGB): \>3 g/dL decrease from BL; total protein: \< 0.9 x LLN, \>1.1 x ULN; albumin:\<0.9 x LLN
Outcome measures
| Measure |
ABA + MTX [DB]
n=124 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=127 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=102 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 729 in Hemoglobin, Total Protein, and Albumin
HGB (n=124, n=125, n=102)
|
0.66 g/dL
Standard Error 0.10
|
0.48 g/dL
Standard Error 0.10
|
0.40 g/dL
Standard Error 0.13
|
|
OL; Mean Change From Baseline to Day 729 in Hemoglobin, Total Protein, and Albumin
Total protein (n=124, n=127, n=102)
|
-0.33 g/dL
Standard Error 0.05
|
-0.25 g/dL
Standard Error 0.04
|
-0.29 g/dL
Standard Error 0.05
|
|
OL; Mean Change From Baseline to Day 729 in Hemoglobin, Total Protein, and Albumin
Albumin (n=124, n=127, n=102)
|
0.13 g/dL
Standard Error 0.03
|
0.10 g/dL
Standard Error 0.03
|
0.06 g/dL
Standard Error 0.03
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 729Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Platelets (PLT): \<0.67 x LLN, \>1.5 x ULN
Outcome measures
| Measure |
ABA + MTX [DB]
n=124 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=122 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=100 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 729 in Platelets
|
-63.9 10^9 c/L
Standard Error 6.04
|
-5832 10^9 c/L
Standard Error 7.66
|
-47.7 10^9 c/L
Standard Error 8.16
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 729Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Hematocrit: \<0.75 x BL
Outcome measures
| Measure |
ABA + MTX [DB]
n=124 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=124 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=102 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 729 in Hematocrit
|
1.72 percentage of red blood cells
Standard Error 0.29
|
1.23 percentage of red blood cells
Standard Error 0.29
|
0.99 percentage of red blood cells
Standard Error 0.38
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 729Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=124 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=125 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=102 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 729 in White Blood Cells
Leukocytes (n=124, n=125, n=102)
|
-1.57 10^3 c/uL
Standard Error 0.23
|
-1.23 10^3 c/uL
Standard Error 0.26
|
-1.28 10^3 c/uL
Standard Error 0.23
|
|
OL; Mean Change From Baseline to Day 729 in White Blood Cells
Neutrophils + bands (n=123, n=123, n=101)
|
-1.62 10^3 c/uL
Standard Error 0.21
|
-1.35 10^3 c/uL
Standard Error 0.23
|
-1.33 10^3 c/uL
Standard Error 0.22
|
|
OL; Mean Change From Baseline to Day 729 in White Blood Cells
Basophils (n=123, n=123, n=101)
|
-0.01 10^3 c/uL
Standard Error 0.00
|
0.00 10^3 c/uL
Standard Error 0.00
|
-0.01 10^3 c/uL
Standard Error 0.00
|
|
OL; Mean Change From Baseline to Day 729 in White Blood Cells
Monocytes (n=123, n=123, n=101)
|
-0.05 10^3 c/uL
Standard Error 0.02
|
-0.02 10^3 c/uL
Standard Error 0.04
|
-0.03 10^3 c/uL
Standard Error 0.02
|
|
OL; Mean Change From Baseline to Day 729 in White Blood Cells
Eosinophils (n=123, n=123, n=101)
|
-0.01 10^3 c/uL
Standard Error 0.01
|
-0.03 10^3 c/uL
Standard Error 0.02
|
-0.05 10^3 c/uL
Standard Error 0.02
|
|
OL; Mean Change From Baseline to Day 729 in White Blood Cells
Lymphocytes (n=123, n=123, n=101)
|
0.13 10^3 c/uL
Standard Error 0.06
|
0.18 10^3 c/uL
Standard Error 0.06
|
0.08 10^3 c/uL
Standard Error 0.06
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 729Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Erythrocytes: \<0.75 x BL
Outcome measures
| Measure |
ABA + MTX [DB]
n=124 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=125 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=102 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 729 in Erythrocytes
|
0.07 10^6 c/uL
Standard Error 0.03
|
0.04 10^6 c/uL
Standard Error 0.03
|
0.02 10^6 c/uL
Standard Error 0.04
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 729Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
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
Outcome measures
| Measure |
ABA + MTX [DB]
n=124 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=127 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=102 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 729 in Electrolytes
Na
|
-1.10 mEq/L
Standard Error 0.28
|
-1.12 mEq/L
Standard Error 0.29
|
-1.22 mEq/L
Standard Error 0.38
|
|
OL; Mean Change From Baseline to Day 729 in Electrolytes
K
|
-0.03 mEq/L
Standard Error 0.04
|
-0.04 mEq/L
Standard Error 0.04
|
-0.02 mEq/L
Standard Error 0.04
|
|
OL; Mean Change From Baseline to Day 729 in Electrolytes
Cl
|
-1.31 mEq/L
Standard Error 0.26
|
-1.28 mEq/L
Standard Error 0.31
|
-2.03 mEq/L
Standard Error 0.29
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 729Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
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;
Outcome measures
| Measure |
ABA + MTX [DB]
n=124 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=127 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=102 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 729 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Creatinine (n=124, n=127, n=102)
|
0.08 mg/dL
Standard Error 0.02
|
0.08 mg/dL
Standard Error 0.01
|
0.07 mg/dL
Standard Error 0.02
|
|
OL; Mean Change From Baseline to Day 729 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
BUN (n=124, n=127, n=102)
|
-0.37 mg/dL
Standard Error 0.43
|
-0.12 mg/dL
Standard Error 0.44
|
0.20 mg/dL
Standard Error 0.46
|
|
OL; Mean Change From Baseline to Day 729 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Ca (n=124, n=127, n=102)
|
0.01 mg/dL
Standard Error 0.04
|
-0.01 mg/dL
Standard Error 0.05
|
0.02 mg/dL
Standard Error 0.05
|
|
OL; Mean Change From Baseline to Day 729 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
P (n=124, n=127, n=102)
|
-0.05 mg/dL
Standard Error 0.05
|
-0.16 mg/dL
Standard Error 0.06
|
-0.08 mg/dL
Standard Error 0.06
|
|
OL; Mean Change From Baseline to Day 729 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Uric Acid (n=124, n=127, n=102)
|
-0.22 mg/dL
Standard Error 0.08
|
-0.02 mg/dL
Standard Error 0.09
|
-0.10 mg/dL
Standard Error 0.12
|
|
OL; Mean Change From Baseline to Day 729 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Total bilirubin (n=124, n=127, n=101)
|
0.01 mg/dL
Standard Error 0.02
|
0.04 mg/dL
Standard Error 0.02
|
0.03 mg/dL
Standard Error 0.02
|
|
OL; Mean Change From Baseline to Day 729 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Serum glucose (n=123, n=126, n=101)
|
9.92 mg/dL
Standard Error 3.04
|
7.52 mg/dL
Standard Error 2.02
|
3.74 mg/dL
Standard Error 2.17
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 729Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
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
Outcome measures
| Measure |
ABA + MTX [DB]
n=124 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=127 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=102 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 729 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
ALT
|
2.73 U/L
Standard Error 1.59
|
1.02 U/L
Standard Error 1.83
|
-0.89 U/L
Standard Error 1.96
|
|
OL; Mean Change From Baseline to Day 729 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
AST
|
0.03 U/L
Standard Error 1.17
|
-0.22 U/L
Standard Error 1.22
|
-2.45 U/L
Standard Error 1.60
|
|
OL; Mean Change From Baseline to Day 729 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
GGT
|
1.23 U/L
Standard Error 2.38
|
-0.41 U/L
Standard Error 2.14
|
-1.93 U/L
Standard Error 2.95
|
|
OL; Mean Change From Baseline to Day 729 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
ALP
|
-0.55 U/L
Standard Error 2.17
|
-2.61 U/L
Standard Error 2.83
|
-3.91 U/L
Standard Error 3.41
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 1121Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Hemoglobin (HGB): \>3 g/dL decrease from BL; total protein: \< 0.9 x LLN, \>1.1 x ULN; albumin:\<0.9 x LLN
Outcome measures
| Measure |
ABA + MTX [DB]
n=102 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=98 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=86 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 1121 in Hemoglobin, Total Protein, and Albumin
HGB (n=102, n=98, n=85)
|
0.66 g/dL
Standard Error 0.13
|
0.53 g/dL
Standard Error 0.14
|
0.57 g/dL
Standard Error 0.13
|
|
OL; Mean Change From Baseline to Day 1121 in Hemoglobin, Total Protein, and Albumin
Total protein (n=102, n=98, n=86)
|
-0.35 g/dL
Standard Error 0.05
|
-0.24 g/dL
Standard Error 0.05
|
-0.33 g/dL
Standard Error 0.05
|
|
OL; Mean Change From Baseline to Day 1121 in Hemoglobin, Total Protein, and Albumin
Albumin (n=102, n=98, n=86)
|
0.04 g/dL
Standard Error 0.04
|
0.08 g/dL
Standard Error 0.04
|
-0.01 g/dL
Standard Error 0.04
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 1121Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Platelets (PLT): \<0.67 x LLN, \>1.5 x ULN
Outcome measures
| Measure |
ABA + MTX [DB]
n=101 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=95 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=85 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 1121 in Platelets
|
-67.5 10^9 c/L
Standard Error 7.49
|
-66.1 10^9 c/L
Standard Error 8.86
|
-62.5 10^9 c/L
Standard Error 8.05
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 1121Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Hematocrit: \<0.75 x BL
Outcome measures
| Measure |
ABA + MTX [DB]
n=100 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=98 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=85 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 1121 in Hematocrit
|
1.83 percentage of red blood cells
Standard Error 0.37
|
1.50 percentage of red blood cells
Standard Error 0.39
|
1.47 percentage of red blood cells
Standard Error 0.39
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 1121Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=102 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=98 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=85 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 1121 in White Blood Cells
Leukocytes (n=102, n=98, n=85)
|
-1.07 10^3 c/uL
Standard Error 0.27
|
-1.09 10^3 c/uL
Standard Error 0.26
|
-0.99 10^3 c/uL
Standard Error 0.25
|
|
OL; Mean Change From Baseline to Day 1121 in White Blood Cells
Neutrophils + bands (n=99, n=96, n=84)
|
-1.17 10^3 c/uL
Standard Error 0.25
|
-1.40 10^3 c/uL
Standard Error 0.25
|
-1.28 10^3 c/uL
Standard Error 0.24
|
|
OL; Mean Change From Baseline to Day 1121 in White Blood Cells
Basophils (n=99, n=96, n=85)
|
0.00 10^3 c/uL
Standard Error 0.00
|
0.00 10^3 c/uL
Standard Error 0.00
|
0.00 10^3 c/uL
Standard Error 0.00
|
|
OL; Mean Change From Baseline to Day 1121 in White Blood Cells
Monocytes (n=99, n=96, n=84)
|
0.03 10^3 c/uL
Standard Error 0.02
|
0.00 10^3 c/uL
Standard Error 0.03
|
0.01 10^3 c/uL
Standard Error 0.03
|
|
OL; Mean Change From Baseline to Day 1121 in White Blood Cells
Eosinophils (n=99, n=96, n=84)
|
0.00 10^3 c/uL
Standard Error 0.01
|
-0.06 10^3 c/uL
Standard Error 0.02
|
-0.04 10^3 c/uL
Standard Error 0.02
|
|
OL; Mean Change From Baseline to Day 1121 in White Blood Cells
Lymphocytes (n=99, n=96, n=84)
|
0.16 10^3 c/uL
Standard Error 0.08
|
0.34 10^3 c/uL
Standard Error 0.07
|
0.32 10^3 c/uL
Standard Error 0.10
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 1121Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Erythrocytes: \<0.75 x BL
Outcome measures
| Measure |
ABA + MTX [DB]
n=102 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=98 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=85 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 1121 in Erythrocytes
|
0.11 10^6 c/uL
Standard Error 0.03
|
0.11 10^6 c/uL
Standard Error 0.04
|
0.12 10^6 c/uL
Standard Error 0.04
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 1121Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
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
Outcome measures
| Measure |
ABA + MTX [DB]
n=102 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=98 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=86 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 1121 in Electrolytes
Na (n=102, n=98, n=86)
|
-1.80 mEq/L
Standard Error 0.33
|
-1.38 mEq/L
Standard Error 0.38
|
-1.34 mEq/L
Standard Error 0.42
|
|
OL; Mean Change From Baseline to Day 1121 in Electrolytes
K (n=102, n=98, n=85)
|
0.01 mEq/L
Standard Error 0.04
|
0.08 mEq/L
Standard Error 0.05
|
0.01 mEq/L
Standard Error 0.05
|
|
OL; Mean Change From Baseline to Day 1121 in Electrolytes
Cl (n=102, n=98, n=86)
|
-0.88 mEq/L
Standard Error 0.35
|
-0.94 mEq/L
Standard Error 0.38
|
-1.42 mEq/L
Standard Error 0.37
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 1121Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
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;
Outcome measures
| Measure |
ABA + MTX [DB]
n=102 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=98 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=86 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 1121 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Creatinine (n=102, n=98, n=86)
|
0.06 mg/dL
Standard Error 0.02
|
0.07 mg/dL
Standard Error 0.03
|
0.08 mg/dL
Standard Error 0.02
|
|
OL; Mean Change From Baseline to Day 1121 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
BUN (n=102, n=98, n=86)
|
-0.04 mg/dL
Standard Error 0.49
|
0.34 mg/dL
Standard Error 0.73
|
0.20 mg/dL
Standard Error 0.56
|
|
OL; Mean Change From Baseline to Day 1121 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Ca (n=102, n=98, n=86)
|
-0.01 mg/dL
Standard Error 0.05
|
-0.03 mg/dL
Standard Error 0.06
|
0.04 mg/dL
Standard Error 0.05
|
|
OL; Mean Change From Baseline to Day 1121 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
P (n=102, n=98, n=85)
|
-0.18 mg/dL
Standard Error 0.07
|
-0.19 mg/dL
Standard Error 0.07
|
-0.11 mg/dL
Standard Error 0.06
|
|
OL; Mean Change From Baseline to Day 1121 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Uric Acid (n=102, n=98, n=86)
|
-0.05 mg/dL
Standard Error 0.11
|
0.13 mg/dL
Standard Error 0.10
|
0.20 mg/dL
Standard Error 0.15
|
|
OL; Mean Change From Baseline to Day 1121 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Total bilirubin (n=102, n=98, n=86)
|
0.02 mg/dL
Standard Error 0.02
|
0.03 mg/dL
Standard Error 0.02
|
0.03 mg/dL
Standard Error 0.02
|
|
OL; Mean Change From Baseline to Day 1121 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Serum glucose (n=101, n=98, n=85)
|
12.99 mg/dL
Standard Error 3.31
|
6.91 mg/dL
Standard Error 2.10
|
9.07 mg/dL
Standard Error 3.20
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 1121Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
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
Outcome measures
| Measure |
ABA + MTX [DB]
n=102 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=98 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=86 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 1121 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
ALT (n=102, n=98, n=86)
|
4.74 U/L
Standard Error 1.95
|
4.66 U/L
Standard Error 2.88
|
-0.35 U/L
Standard Error 2.33
|
|
OL; Mean Change From Baseline to Day 1121 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
AST (n=102, n=98, n=86)
|
3.79 U/L
Standard Error 1.60
|
4.49 U/L
Standard Error 2.13
|
0.38 U/L
Standard Error 1.69
|
|
OL; Mean Change From Baseline to Day 1121 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
GGT (n=102, n=98, n=86)
|
1.60 U/L
Standard Error 2.79
|
-2.88 U/L
Standard Error 2.16
|
-0.14 U/L
Standard Error 3.79
|
|
OL; Mean Change From Baseline to Day 1121 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
ALP (n=88, n=79, n=69)
|
1.25 U/L
Standard Error 2.62
|
-4.03 U/L
Standard Error 3.79
|
-7.35 U/L
Standard Error 3.53
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 1513Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Hemoglobin (HGB): \>3 g/dL decrease from BL; total protein: \< 0.9 x LLN, \>1.1 x ULN; albumin:\<0.9 x LLN
Outcome measures
| Measure |
ABA + MTX [DB]
n=23 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=20 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=16 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 1513 in Hemoglobin, Total Protein, and Albumin
HGB
|
0.25 g/dL
Standard Error 0.33
|
0.44 g/dL
Standard Error 0.31
|
0.56 g/dL
Standard Error 0.32
|
|
OL; Mean Change From Baseline to Day 1513 in Hemoglobin, Total Protein, and Albumin
Total protein
|
-0.73 g/dL
Standard Error 0.09
|
-0.33 g/dL
Standard Error 0.11
|
-0.34 g/dL
Standard Error 0.14
|
|
OL; Mean Change From Baseline to Day 1513 in Hemoglobin, Total Protein, and Albumin
Albumin
|
-0.06 g/dL
Standard Error 0.07
|
0.10 g/dL
Standard Error 0.07
|
0.00 g/dL
Standard Error 0.11
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 1513Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Platelets (PLT): \<0.67 x LLN, \>1.5 x ULN
Outcome measures
| Measure |
ABA + MTX [DB]
n=23 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=19 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=16 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 1513 in Platelets
|
-78.0 10^9 c/L
Standard Error 17.20
|
-74.0 10^9 c/L
Standard Error 16.18
|
-99.2 10^9 c/L
Standard Error 19.83
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 1513Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Hematocrit: \<0.75 x BL
Outcome measures
| Measure |
ABA + MTX [DB]
n=23 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=19 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=16 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 1513 in Hematocrit
|
0.92 percentage of red blood cells
Standard Error 1.00
|
1.28 percentage of red blood cells
Standard Error 0.92
|
1.18 percentage of red blood cells
Standard Error 1.00
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 1513Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=23 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=20 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=16 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 1513 in White Blood Cells
Leukocytes (n=23, n=20, n=16)
|
-0.34 10^3 c/uL
Standard Error 0.45
|
-1.08 10^3 c/uL
Standard Error 0.63
|
-2.13 10^3 c/uL
Standard Error 0.50
|
|
OL; Mean Change From Baseline to Day 1513 in White Blood Cells
Neutrophils + bands (n=22, n=17, n=16)
|
-0.37 10^3 c/uL
Standard Error 0.33
|
-1.03 10^3 c/uL
Standard Error 0.68
|
-1.93 10^3 c/uL
Standard Error 0.50
|
|
OL; Mean Change From Baseline to Day 1513 in White Blood Cells
Basophils (n=22, n=17, n=16)
|
0.00 10^3 c/uL
Standard Error 0.01
|
-0.01 10^3 c/uL
Standard Error 0.01
|
-0.01 10^3 c/uL
Standard Error 0.01
|
|
OL; Mean Change From Baseline to Day 1513 in White Blood Cells
Monocytes (n=22, n=17, n=16)
|
0.01 10^3 c/uL
Standard Error 0.03
|
-0.10 10^3 c/uL
Standard Error 0.09
|
-0.05 10^3 c/uL
Standard Error 0.04
|
|
OL; Mean Change From Baseline to Day 1513 in White Blood Cells
Eosinophils (n=22, n=17, n=16)
|
0.04 10^3 c/uL
Standard Error 0.06
|
-0.11 10^3 c/uL
Standard Error 0.16
|
-0.23 10^3 c/uL
Standard Error 0.00
|
|
OL; Mean Change From Baseline to Day 1513 in White Blood Cells
Lymphocytes (n=22, n=17, n=16)
|
0.20 10^3 c/uL
Standard Error 0.14
|
0.16 10^3 c/uL
Standard Error 0.16
|
-0.15 10^3 c/uL
Standard Error 0.16
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 1513Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
Erythrocytes: \<0.75 x BL
Outcome measures
| Measure |
ABA + MTX [DB]
n=23 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=19 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=16 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 1513 in Erythrocytes
|
-0.10 10^6 c/uL
Standard Error 0.09
|
0.00 10^6 c/uL
Standard Error 0.09
|
-0.09 10^6 c/uL
Standard Error 0.08
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 1513Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
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
Outcome measures
| Measure |
ABA + MTX [DB]
n=23 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=20 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=16 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 1513 in Electrolytes
Na (n=22, n=20, n=16)
|
-4.36 mEq/L
Standard Error 0.73
|
-3.80 mEq/L
Standard Error 0.99
|
-4.50 mEq/L
Standard Error 0.74
|
|
OL; Mean Change From Baseline to Day 1513 in Electrolytes
K (n=23, n=20, n=16)
|
-0.16 mEq/L
Standard Error 0.10
|
-0.32 mEq/L
Standard Error 0.08
|
-0.46 mEq/L
Standard Error 0.11
|
|
OL; Mean Change From Baseline to Day 1513 in Electrolytes
Cl (n=23, n=20, n=16)
|
-2.48 mEq/L
Standard Error 0.71
|
-2.60 mEq/L
Standard Error 0.84
|
-4.13 mEq/L
Standard Error 0.88
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 1513Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
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;
Outcome measures
| Measure |
ABA + MTX [DB]
n=23 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=20 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=16 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 1513 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Serum glucose
|
8.87 mg/dL
Standard Error 3.19
|
9.00 mg/dL
Standard Error 1.88
|
8.44 mg/dL
Standard Error 4.38
|
|
OL; Mean Change From Baseline to Day 1513 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Creatinine
|
0.10 mg/dL
Standard Error 0.02
|
0.05 mg/dL
Standard Error 0.04
|
0.08 mg/dL
Standard Error 0.06
|
|
OL; Mean Change From Baseline to Day 1513 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
BUN
|
2.87 mg/dL
Standard Error 0.90
|
-0.40 mg/dL
Standard Error 1.13
|
0.63 mg/dL
Standard Error 1.36
|
|
OL; Mean Change From Baseline to Day 1513 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Ca
|
0.27 mg/dL
Standard Error 0.07
|
0.38 mg/dL
Standard Error 0.09
|
0.35 mg/dL
Standard Error 0.12
|
|
OL; Mean Change From Baseline to Day 1513 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
P
|
-0.09 mg/dL
Standard Error 0.11
|
-0.51 mg/dL
Standard Error 0.16
|
-0.17 mg/dL
Standard Error 0.13
|
|
OL; Mean Change From Baseline to Day 1513 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Uric Acid
|
0.03 mg/dL
Standard Error 0.18
|
0.06 mg/dL
Standard Error 0.21
|
0.33 mg/dL
Standard Error 0.33
|
|
OL; Mean Change From Baseline to Day 1513 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Total bilirubin
|
0.08 mg/dL
Standard Error 0.10
|
0.09 mg/dL
Standard Error 0.03
|
0.23 mg/dL
Standard Error 0.14
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 1513Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
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
Outcome measures
| Measure |
ABA + MTX [DB]
n=23 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=20 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=16 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline to Day 1513 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
ALT
|
-1.87 U/L
Standard Error 2.73
|
-9.20 U/L
Standard Error 3.75
|
2.44 U/L
Standard Error 8.07
|
|
OL; Mean Change From Baseline to Day 1513 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
AST
|
-1.35 U/L
Standard Error 1.72
|
-2.85 U/L
Standard Error 2.55
|
0.38 U/L
Standard Error 7.23
|
|
OL; Mean Change From Baseline to Day 1513 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
GGT
|
-3.00 U/L
Standard Error 2.99
|
-10.9 U/L
Standard Error 5.79
|
-3.06 U/L
Standard Error 10.30
|
|
OL; Mean Change From Baseline to Day 1513 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
ALP
|
-15.8 U/L
Standard Error 5.23
|
-18.7 U/L
Standard Error 7.12
|
-11.30 U/L
Standard Error 7.80
|
PRIMARY outcome
Timeframe: Days 365, 729, 1121, and 1513Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.n=number of participants with data available.
Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP), units=mm mercury (Hg)
Outcome measures
| Measure |
ABA + MTX [DB]
n=372 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Day 365 SBP pre-dose (n=343)
|
119.0 mm mercury (Hg)
Standard Deviation 15.03
|
—
|
—
|
|
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Day 365 SBP post-dose (n=341)
|
118.8 mm mercury (Hg)
Standard Deviation 15.35
|
—
|
—
|
|
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Day 729 SBP pre-dose (n=321)
|
120.4 mm mercury (Hg)
Standard Deviation 15.20
|
—
|
—
|
|
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Day 729 SBP post-dose (n=323)
|
119.5 mm mercury (Hg)
Standard Deviation 15.02
|
—
|
—
|
|
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Day 1121 SBP pre-dose (n=265)
|
121.1 mm mercury (Hg)
Standard Deviation 15.59
|
—
|
—
|
|
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Day 1121 SBP post-dose (n=265)
|
119.2 mm mercury (Hg)
Standard Deviation 13.99
|
—
|
—
|
|
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Day 1513 SBP pre-dose (n=52)
|
114.6 mm mercury (Hg)
Standard Deviation 13.57
|
—
|
—
|
|
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Day 1513 SBP post-dose (n=52)
|
114.2 mm mercury (Hg)
Standard Deviation 12.90
|
—
|
—
|
|
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Day 365 DBP pre-dose (n=343)
|
74.5 mm mercury (Hg)
Standard Deviation 9.80
|
—
|
—
|
|
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Day 365 DBP post-dose (n=341)
|
74.0 mm mercury (Hg)
Standard Deviation 10.18
|
—
|
—
|
|
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Day 729 DBP pre-dose (n=321)
|
74.9 mm mercury (Hg)
Standard Deviation 9.69
|
—
|
—
|
|
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Day 729 DBP post-dose (n=323)
|
74.6 mm mercury (Hg)
Standard Deviation 9.92
|
—
|
—
|
|
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Day 1121 DBP pre-dose (n=265)
|
74.9 mm mercury (Hg)
Standard Deviation 9.45
|
—
|
—
|
|
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Day 1121 DBP post-dose (n=265)
|
73.6 mm mercury (Hg)
Standard Deviation 9.12
|
—
|
—
|
|
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Day 1513 DBP pre-dose (n=52)
|
71.7 mm mercury (Hg)
Standard Deviation 9.45
|
—
|
—
|
|
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Day 1513 DBP post-dose (n=52)
|
72.1 mm mercury (Hg)
Standard Deviation 9.11
|
—
|
—
|
PRIMARY outcome
Timeframe: Days 365, 729, 1121, and 1513Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.n=number of participants with data available.
Heart Rate (HR), units=beats per minute (bpm)
Outcome measures
| Measure |
ABA + MTX [DB]
n=372 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Heart Rate (HR) During Open Label Period
Day 365 HR pre-dose (n=343)
|
74.2 beats per minute (bpm)
Standard Deviation 9.30
|
—
|
—
|
|
OL; Mean Heart Rate (HR) During Open Label Period
Day 365 HR post-dose (n=341)
|
74.1 beats per minute (bpm)
Standard Deviation 8.57
|
—
|
—
|
|
OL; Mean Heart Rate (HR) During Open Label Period
Day 729 HR pre-dose (n=322)
|
74.2 beats per minute (bpm)
Standard Deviation 9.12
|
—
|
—
|
|
OL; Mean Heart Rate (HR) During Open Label Period
Day 729 HR post-dose (n=324)
|
73.4 beats per minute (bpm)
Standard Deviation 8.59
|
—
|
—
|
|
OL; Mean Heart Rate (HR) During Open Label Period
Day 1121 HR pre-dose (n=265)
|
73.9 beats per minute (bpm)
Standard Deviation 9.31
|
—
|
—
|
|
OL; Mean Heart Rate (HR) During Open Label Period
Day 1121 HR post-dose (n=265)
|
73.8 beats per minute (bpm)
Standard Deviation 9.46
|
—
|
—
|
|
OL; Mean Heart Rate (HR) During Open Label Period
Day 1513 HR pre-dose (n=52)
|
73.0 beats per minute (bpm)
Standard Deviation 8.38
|
—
|
—
|
|
OL; Mean Heart Rate (HR) During Open Label Period
Day 1513 HR post-dose (n=52)
|
73.8 beats per minute (bpm)
Standard Deviation 7.16
|
—
|
—
|
PRIMARY outcome
Timeframe: Days 365, 729, 1121, and 1513Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period.n=number of participants with data available.
Temperature (T), units=degrees Celcius
Outcome measures
| Measure |
ABA + MTX [DB]
n=372 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Temperature (T) During Open Label Period
Day 365 T pre-dose (n=339)
|
36.3 degrees Celsius
Standard Deviation 0.43
|
—
|
—
|
|
OL; Mean Temperature (T) During Open Label Period
Day 365 T post-dose (n=339)
|
36.3 degrees Celsius
Standard Deviation 0.41
|
—
|
—
|
|
OL; Mean Temperature (T) During Open Label Period
Day 729 T pre-dose (n=320)
|
36.3 degrees Celsius
Standard Deviation 0.45
|
—
|
—
|
|
OL; Mean Temperature (T) During Open Label Period
Day 729 T post-dose (n=323)
|
36.3 degrees Celsius
Standard Deviation 0.42
|
—
|
—
|
|
OL; Mean Temperature (T) During Open Label Period
Day 1121 T pre-dose (n=263)
|
36.2 degrees Celsius
Standard Deviation 0.51
|
—
|
—
|
|
OL; Mean Temperature (T) During Open Label Period
Day 1121 T post-dose (n=264)
|
36.2 degrees Celsius
Standard Deviation 0.47
|
—
|
—
|
|
OL; Mean Temperature (T) During Open Label Period
Day 1513 T pre-dose (n=52)
|
36.1 degrees Celsius
Standard Deviation 0.35
|
—
|
—
|
|
OL; Mean Temperature (T) During Open Label Period
Day 1513 T post-dose (n=52)
|
36.1 degrees Celsius
Standard Deviation 0.37
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1), 6 months (Day 197)Population: The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=156 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=102 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Adjusted Mean Change From Baseline to Day 197 in DAS 28 Score (ESR) For INF Versus PLA (LOCF Analysis)
|
-2.25 units on a scale
Standard Error 0.12
|
-1.48 units on a scale
Standard Error 0.15
|
—
|
SECONDARY outcome
Timeframe: From Day 1 through Day 365 (12 months)Population: The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=150 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=156 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; DAS 28 (ESR) Area Under The Curve (AUC) Over 12 Months For ABA Versus INF
|
1638.6 units on a scale
Standard Deviation 395.81
|
1657.5 units on a scale
Standard Deviation 460.52
|
—
|
SECONDARY outcome
Timeframe: DB Day 197Population: The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=156 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=165 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=110 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 197
|
61.5 percentage of participants
|
58.8 percentage of participants
|
40.9 percentage of participants
|
SECONDARY outcome
Timeframe: DB Day 365Population: The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=156 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=165 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=110 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 365
|
57.7 percentage of participants
|
52.7 percentage of participants
|
57.3 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1), 6 months (Day 197)Population: The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=156 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=164 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=109 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis)
HAQ-DI component: activities
|
-0.61 units on a scale
Standard Error 0.06
|
-0.54 units on a scale
Standard Error 0.06
|
-0.22 units on a scale
Standard Error 0.08
|
|
DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis)
HAQ-DI component: dressing and grooming
|
-0.69 units on a scale
Standard Error 0.06
|
-0.57 units on a scale
Standard Error 0.06
|
-0.37 units on a scale
Standard Error 0.07
|
|
DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis)
HAQ-DI component: eating
|
-0.79 units on a scale
Standard Error 0.06
|
-0.77 units on a scale
Standard Error 0.06
|
-0.36 units on a scale
Standard Error 0.08
|
|
DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis)
HAQ-DI component: grip
|
-0.73 units on a scale
Standard Error 0.07
|
-0.70 units on a scale
Standard Error 0.07
|
-0.26 units on a scale
Standard Error 0.08
|
|
DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis)
HAQ-DI component: hygiene
|
-0.64 units on a scale
Standard Error 0.07
|
-0.48 units on a scale
Standard Error 0.07
|
-0.26 units on a scale
Standard Error 0.08
|
|
DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis)
HAQ-DI component: reach
|
-0.72 units on a scale
Standard Error 0.07
|
-0.64 units on a scale
Standard Error 0.07
|
-0.30 units on a scale
Standard Error 0.08
|
|
DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis)
HAQ-DI component: arising
|
-0.70 units on a scale
Standard Error 0.06
|
-0.68 units on a scale
Standard Error 0.06
|
-0.39 units on a scale
Standard Error 0.07
|
|
DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis)
HAQ-DI component: walking
|
-0.58 units on a scale
Standard Error 0.06
|
-0.56 units on a scale
Standard Error 0.06
|
-0.23 units on a scale
Standard Error 0.07
|
|
DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis)
HAQ-DI
|
-0.69 units on a scale
Standard Error 0.05
|
-0.61 units on a scale
Standard Error 0.05
|
-0.31 units on a scale
Standard Error 0.06
|
SECONDARY outcome
Timeframe: Baseline (Day 1), 12 months (Day 365)Population: Intent-to-Treat (ITT) Population: all participants randomized into the study receiving study medication, grouped according to randomization treatment. All participants randomized but never receiving study medication excluded. Although 3 participants in PLA group discontinued before Day 197, 2 of these patients were included in the 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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=156 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=164 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=109 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis)
HAQ-DI
|
-0.67 units on a scale
Standard Error 0.05
|
-0.59 units on a scale
Standard Error 0.05
|
-0.56 units on a scale
Standard Error 0.06
|
|
DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis)
HAQ-DI component: activities
|
-0.55 units on a scale
Standard Error 0.07
|
-0.52 units on a scale
Standard Error 0.07
|
-0.55 units on a scale
Standard Error 0.08
|
|
DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis)
HAQ-DI component: dressing and grooming
|
-0.72 units on a scale
Standard Error 0.06
|
-0.60 units on a scale
Standard Error 0.06
|
-0.56 units on a scale
Standard Error 0.07
|
|
DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis)
HAQ-DI component: eating
|
-0.80 units on a scale
Standard Error 0.06
|
-0.73 units on a scale
Standard Error 0.06
|
-0.71 units on a scale
Standard Error 0.08
|
|
DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis)
HAQ-DI component: grip
|
-0.77 units on a scale
Standard Error 0.07
|
-0.64 units on a scale
Standard Error 0.07
|
-0.56 units on a scale
Standard Error 0.08
|
|
DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis)
HAQ-DI component: hygiene
|
-0.53 units on a scale
Standard Error 0.07
|
-0.45 units on a scale
Standard Error 0.07
|
-0.42 units on a scale
Standard Error 0.09
|
|
DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis)
HAQ-DI component: reach
|
-0.77 units on a scale
Standard Error 0.07
|
-0.66 units on a scale
Standard Error 0.07
|
-0.53 units on a scale
Standard Error 0.08
|
|
DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis)
HAQ-DI component: arising
|
-0.68 units on a scale
Standard Error 0.06
|
-0.64 units on a scale
Standard Error 0.06
|
-0.61 units on a scale
Standard Error 0.07
|
|
DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis)
HAQ-DI component: walking
|
-0.54 units on a scale
Standard Error 0.06
|
-0.55 units on a scale
Standard Error 0.06
|
-0.47 units on a scale
Standard Error 0.07
|
SECONDARY outcome
Timeframe: Baseline (Day 1), 6 months (Day 197)Population: ITT population, all participants randomized into the study receiving study medication. Participants grouped according to the treatment to which they were randomized. All randomized participants who never received study medication were excluded. SF-36 component scores were not presented in tabular form.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=154 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=163 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=109 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Adjusted Mean Change From Baseline to Day 197 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)
SF-36 Physical Component Summary
|
8.36 units on a scale
Standard Error 0.69
|
7.66 units on a scale
Standard Error 0.67
|
4.34 units on a scale
Standard Error 0.82
|
|
DB; Adjusted Mean Change From Baseline to Day 197 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)
SF-36 Mental Component Summary
|
5.14 units on a scale
Standard Error 0.79
|
4.32 units on a scale
Standard Error 0.76
|
1.64 units on a scale
Standard Error 0.93
|
SECONDARY outcome
Timeframe: Baseline (Day 1), 12 months (Day 365)Population: ITT Population: all participants randomized into the study receiving study medication, grouped according to randomization treatment. Although 3 participants in PLA group discontinued before Day 197, 2 of these patients were included in the LOCF analysis. SF-36 component scores were not presented in tabular form.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=154 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=163 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=109 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Adjusted Mean Change From Baseline to Day 365 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)
SF-36 Physical Component Summary
|
9.52 units on a scale
Standard Error 0.70
|
7.59 units on a scale
Standard Error 0.68
|
8.00 units on a scale
Standard Error 0.83
|
|
DB; Adjusted Mean Change From Baseline to Day 365 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)
SF-36 Mental Component Summary
|
5.96 units on a scale
Standard Error 0.81
|
4.03 units on a scale
Standard Error 0.79
|
5.85 units on a scale
Standard Error 0.97
|
SECONDARY outcome
Timeframe: DB Day 365Population: The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.
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)
Outcome measures
| Measure |
ABA + MTX [DB]
n=150 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=157 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=102 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) at Day 365
No response
|
27.3 percentage of participants
|
36.3 percentage of participants
|
23.5 percentage of participants
|
|
DB; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) at Day 365
Moderate response
|
40.7 percentage of participants
|
45.2 percentage of participants
|
49.0 percentage of participants
|
|
DB; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) at Day 365
Good response
|
32.0 percentage of participants
|
18.5 percentage of participants
|
27.5 percentage of participants
|
SECONDARY outcome
Timeframe: DB Day 197Population: The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=156 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=165 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=110 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 197
Day 197, ACR 20
|
66.7 percentage of participants
|
59.4 percentage of participants
|
41.8 percentage of participants
|
|
DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 197
Day 197, ACR 50
|
40.4 percentage of participants
|
37.0 percentage of participants
|
20.0 percentage of participants
|
|
DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 197
Day 197, ACR 70
|
20.5 percentage of participants
|
24.2 percentage of participants
|
9.1 percentage of participants
|
SECONDARY outcome
Timeframe: DB Day 365Population: The Intent-to-Treat (ITT) analysis population was defined to include all participants randomized into the study who received study medication. Participants were grouped according to the treatment or treatment regimen to which they were randomized. All participants who were randomized but never received study medication were excluded.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=156 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=165 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=110 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 365
Day 365, ACR 20
|
72.4 percentage of participants
|
55.8 percentage of participants
|
68.2 percentage of participants
|
|
DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 365
Day 365, ACR 50
|
45.5 percentage of participants
|
36.4 percentage of participants
|
50.9 percentage of participants
|
|
DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 365
Day 365, ACR 70
|
26.3 percentage of participants
|
20.6 percentage of participants
|
29.1 percentage of participants
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-studyPopulation: The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=156 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=165 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=110 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
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
Deaths
|
1 participants
|
1 participants
|
0 participants
|
|
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
SAEs
|
8 participants
|
19 participants
|
13 participants
|
|
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
Related SAEs
|
3 participants
|
8 participants
|
3 participants
|
|
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
SAEs Leading to Discontinuation
|
2 participants
|
4 participants
|
0 participants
|
|
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
AEs
|
129 participants
|
140 participants
|
92 participants
|
|
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
Related AEs
|
64 participants
|
74 participants
|
46 participants
|
|
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
AEs Leading to discontinuation
|
3 participants
|
8 participants
|
1 participants
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-studyPopulation: The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.
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).
Outcome measures
| Measure |
ABA + MTX [DB]
n=156 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=165 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=110 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 197
Pre-specified infections
|
12 participants
|
18 participants
|
8 participants
|
|
DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 197
Neoplasms: Benign, malignant, and unspecified
|
1 participants
|
2 participants
|
1 participants
|
|
DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 197
Prespecified autoimmune symptoms and disorders
|
1 participants
|
1 participants
|
1 participants
|
|
DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 197
Pre-specified infusional AEs
|
8 participants
|
30 participants
|
11 participants
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-studyPopulation: The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=156 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=165 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
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
Deaths
|
1 participants
|
2 participants
|
—
|
|
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
SAEs
|
15 participants
|
30 participants
|
—
|
|
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
Related SAEs
|
5 participants
|
14 participants
|
—
|
|
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
SAEs Leading to Discontinuation
|
4 participants
|
6 participants
|
—
|
|
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
AEs
|
139 participants
|
154 participants
|
—
|
|
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
Related AEs
|
72 participants
|
96 participants
|
—
|
|
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
AEs Leading to discontinuation
|
5 participants
|
12 participants
|
—
|
SECONDARY outcome
Timeframe: From Day 198 through Day 365, and up to 56 days after last dose if occurring on-studyPopulation: The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=110 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
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
Deaths
|
1 participants
|
—
|
—
|
|
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
SAEs
|
12 participants
|
—
|
—
|
|
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
Related SAEs
|
3 participants
|
—
|
—
|
|
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
SAEs Leading to Discontinuation
|
0 participants
|
—
|
—
|
|
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
AEs
|
71 participants
|
—
|
—
|
|
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
Related AEs
|
26 participants
|
—
|
—
|
|
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
AEs Leading to discontinuation
|
0 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-studyPopulation: The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.
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).
Outcome measures
| Measure |
ABA + MTX [DB]
n=156 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=165 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 365
Pre-specified infections
|
16 participants
|
30 participants
|
—
|
|
DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 365
Neoplasms:Benign, malignant, and unspecified
|
1 participants
|
2 participants
|
—
|
|
DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 365
Prespecified autoimmune symptoms and disorders
|
2 participants
|
1 participants
|
—
|
|
DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 365
Pre-specified infusional AEs
|
11 participants
|
41 participants
|
—
|
SECONDARY outcome
Timeframe: From Day 198 through Day 365, and up to 56 days after last dose if occurring on-studyPopulation: The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.
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).
Outcome measures
| Measure |
ABA + MTX [DB]
n=110 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Number of Participants With AEs of Special Interest From Day 198 Through Day 365 in Participants Receiving Placebo Switched to Abatacept
Pre-specified infections
|
3 participants
|
—
|
—
|
|
DB; Number of Participants With AEs of Special Interest From Day 198 Through Day 365 in Participants Receiving Placebo Switched to Abatacept
Prespecified autoimmune symptoms and disorders
|
1 participants
|
—
|
—
|
|
DB; Number of Participants With AEs of Special Interest From Day 198 Through Day 365 in Participants Receiving Placebo Switched to Abatacept
Pre-specified infusional AEs
|
5 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) through Day 197, or Day 1 through Day 365, and up to 56 days after last dose if occurring on-studyPopulation: As-Treated Population
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=156 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=165 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=110 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Number of Participants With Significant Changes in Mean Systolic and Diastolic Blood Pressure During Days 1 Through 197 and Days 1 Through 365
Days 1-197
|
0 participants
|
0 participants
|
0 participants
|
|
DB; Number of Participants With Significant Changes in Mean Systolic and Diastolic Blood Pressure During Days 1 Through 197 and Days 1 Through 365
Days 1-365
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) through Day 197, or Day 1 through Day 365, and up to 56 days after last dose if occurring on-studyPopulation: As Treated Population.
Heart Rate (HR) was assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
Outcome measures
| Measure |
ABA + MTX [DB]
n=156 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=165 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=110 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Number of Participants With Significant Changes in Mean Heart Rate During Days 1 Through 197 and Days 1 Through 365
Days 1-197
|
0 participants
|
0 participants
|
0 participants
|
|
DB; Number of Participants With Significant Changes in Mean Heart Rate During Days 1 Through 197 and Days 1 Through 365
Days 1-365
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-studyPopulation: As Treated Population.
Temperature (T) was assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
Outcome measures
| Measure |
ABA + MTX [DB]
n=156 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=165 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=110 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Number of Participants With Significant Changes in Mean Temperature During Days 1 Through 197 and Days 1 Through 365
Days 1-197
|
0 participants
|
0 participants
|
0 participants
|
|
DB; Number of Participants With Significant Changes in Mean Temperature During Days 1 Through 197 and Days 1 Through 365
Days 1-365
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-studyPopulation: The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.
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
Outcome measures
| Measure |
ABA + MTX [DB]
n=155 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=162 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=108 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197
Low HGB (n=155, n=162, n=108)
|
1 participants
|
1 participants
|
1 participants
|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197
Low hematocrit (n=155, n=162, n=108)
|
0 participants
|
2 participants
|
0 participants
|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197
Low PLT (n=154, n=160, n=108)
|
1 participants
|
2 participants
|
0 participants
|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197
High PLT (n=154, n=160, n=108)
|
0 participants
|
0 participants
|
1 participants
|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197
Low leukocytes (n=155, n=162, n=108)
|
0 participants
|
1 participants
|
0 participants
|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197
High leukocytes (n=155, n=162, n=108)
|
6 participants
|
12 participants
|
16 participants
|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197
Low neutrophils + bands (n=155, n=162, n=108)
|
0 participants
|
0 participants
|
1 participants
|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197
High AST (n=155, n=162, n=108)
|
3 participants
|
3 participants
|
1 participants
|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197
High ALT (n=155, n=162, n=108)
|
3 participants
|
2 participants
|
3 participants
|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197
High creatinine (n=155, n=162, n=108)
|
6 participants
|
9 participants
|
5 participants
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-studyPopulation: The As-Treated analysis population contained all participants who received at least one dose of double-blind study medication, and participants were grouped on an as-assigned or randomized basis unless the participant received the incorrect medication for the entire period of treatment.
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
Outcome measures
| Measure |
ABA + MTX [DB]
n=156 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=164 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=109 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365
Low HGB (n=156, n=164, n=109)
|
2 participants
|
1 participants
|
1 participants
|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365
Low hematocrit (n=156, n=164, n=109)
|
1 participants
|
2 participants
|
0 participants
|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365
Low PLT (n=155, n=162, n=109)
|
1 participants
|
2 participants
|
0 participants
|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365
High PLT (n=155, n=162, n=109)
|
0 participants
|
0 participants
|
1 participants
|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365
Low leukocytes (n=156, n=164, n=109)
|
0 participants
|
1 participants
|
0 participants
|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365
High leukocytes (n=156, n=164, n=109)
|
7 participants
|
22 participants
|
20 participants
|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365
Low neutrophils + bands (n=156, n=164, n=109)
|
0 participants
|
0 participants
|
1 participants
|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365
High AST (n=156, n=164, n=109)
|
4 participants
|
6 participants
|
3 participants
|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365
High ALT (n=156, n=164, n=109)
|
3 participants
|
7 participants
|
5 participants
|
|
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365
High creatinine (n=156, n=164, n=109)
|
10 participants
|
13 participants
|
7 participants
|
SECONDARY outcome
Timeframe: Day 1 through day 365Population: The immunogenicity analysis population included participants who received at least one dose of abatacept and had immunogenicity samples collected at baseline and at least one post-baseline treatment visit.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=156 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=110 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Number of Participants With Anti-Abatacept Antibodies From Day 1 Through Day 365 (Electrochemiluminescent [ECL] Immunoassay)
CTLA4 and Possibly Ig
|
0 participants
|
0 participants
|
—
|
|
DB; Number of Participants With Anti-Abatacept Antibodies From Day 1 Through Day 365 (Electrochemiluminescent [ECL] Immunoassay)
Ig and/or Junction
|
0 participants
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: Day 1 through day 365Population: The immunogenicity analysis population included participants who received at least one dose of infliximab and had immunogenicity samples collected at baseline and at least one post-baseline treatment visit.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=163 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Post Day 28 indeterminate anti-HACA
|
27.5 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Discontinued, overall anti-HACA
|
60.9 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Discontinued, overall indeterminate anti-HACA
|
47.8 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Discontinued, post day 28 anti-HACA
|
55.0 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Discontinued, post day 28 indeterminate anti-HACA
|
25.0 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Discontinued, post day 56 anti-HACA
|
72.7 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Discontinued, post day 56 indeterminate anti-HACA
|
9.1 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Discontinued, post day 85 anti-HACA
|
88.9 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Discontinued, post day 85 indeterminate anti-HACA
|
0 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Missed doses, overall anti-HACA
|
73.1 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Missed doses, overall indeterminate anti-HACA
|
76.9 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Missed 1 dose, anti-HACA
|
72.0 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Missed 1 dose, indeterminate anti-HACA
|
76.0 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Missed >1 dose, anti-HACA
|
100.0 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Missed >1 dose, indeterminate anti-HACA
|
100.0 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Day 309 indeterminate anti-HACA
|
29.7 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Post Day 28 anti-HACA
|
52.2 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Overall anti-HACA
|
62.0 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Overall indeterminate anti-HACA
|
73.0 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Day 1 anti-HACA
|
0 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Day 1 indeterminate anti-HACA
|
3.7 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Day 113 anti-HACA
|
20.0 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Day 113 indeterminate anti-HACA
|
74.7 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Day 197 anti-HACA
|
42.2 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Day 197 indeterminate anti-HACA
|
33.3 percentage of participants
|
—
|
—
|
|
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Day 309 anti-HACA
|
53.6 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Day 365, Day 533, Day 729Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period.n=number of participants with data available.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=132 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=136 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=104 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Mean Change From Baseline Over Time in DAS 28 (ESR) Score
Day 365 (n=122, n=130, n=94)
|
-3.12 units on a scale
Standard Error 0.13
|
-2.39 units on a scale
Standard Error 0.13
|
-2.81 units on a scale
Standard Error 0.16
|
|
OL; Mean Change From Baseline Over Time in DAS 28 (ESR) Score
Day 533 (n=118, n=121, n=92)
|
-3.21 units on a scale
Standard Error 0.13
|
-3.04 units on a scale
Standard Error 0.13
|
-2.84 units on a scale
Standard Error 0.17
|
|
OL; Mean Change From Baseline Over Time in DAS 28 (ESR) Score
Day 729 (n=110, n=121, n=93)
|
-3.35 units on a scale
Standard Error 0.14
|
-3.29 units on a scale
Standard Error 0.12
|
-2.98 units on a scale
Standard Error 0.17
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Day 365, Day 533, Day 729Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Efficacy data was summarized for the 3 DB treatment cohorts.n=number of participants with data available.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=132 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=136 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=104 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Percentage of Participants With DAS28 (ESR) Remission and Low Disease Activity (LDAS) Over Time
Day 365 Remission (n=127, n=135, n=102)
|
19.7 percentage of participants
|
13.3 percentage of participants
|
15.7 percentage of participants
|
|
OL; Percentage of Participants With DAS28 (ESR) Remission and Low Disease Activity (LDAS) Over Time
Day 365 LDAS (n=127, n=135, n=102)
|
37.0 percentage of participants
|
23.0 percentage of participants
|
29.4 percentage of participants
|
|
OL; Percentage of Participants With DAS28 (ESR) Remission and Low Disease Activity (LDAS) Over Time
Day 533 Remission (n=122, n=125, n=98)
|
20.5 percentage of participants
|
20.0 percentage of participants
|
19.4 percentage of participants
|
|
OL; Percentage of Participants With DAS28 (ESR) Remission and Low Disease Activity (LDAS) Over Time
Day 533 LDAS (n=122, n=125, n=98)
|
37.7 percentage of participants
|
33.6 percentage of participants
|
35.7 percentage of participants
|
|
OL; Percentage of Participants With DAS28 (ESR) Remission and Low Disease Activity (LDAS) Over Time
Day 729 Remission (n=115, n=126, n=100)
|
26.1 percentage of participants
|
28.6 percentage of participants
|
22.0 percentage of participants
|
|
OL; Percentage of Participants With DAS28 (ESR) Remission and Low Disease Activity (LDAS) Over Time
Day 729 LDAS (n=115, n=126, n=100)
|
41.7 percentage of participants
|
45.2 percentage of participants
|
34.0 percentage of participants
|
SECONDARY outcome
Timeframe: DB Days 365, 533, and 729Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period.n=number of participants with data available.
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)
Outcome measures
| Measure |
ABA + MTX [DB]
n=132 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=136 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=104 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Over Time
Day 365 Good response (n=122, n=130, n=94)
|
38.5 percentage of participants
|
23.1 percentage of participants
|
30.9 percentage of participants
|
|
OL; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Over Time
Day 365 Moderate response (n=122, n=130, n=94)
|
53.3 percentage of participants
|
58.5 percentage of participants
|
55.3 percentage of participants
|
|
OL; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Over Time
Day 365 No response (n=122, n=130, n=94)
|
8.2 percentage of participants
|
18.5 percentage of participants
|
13.8 percentage of participants
|
|
OL; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Over Time
Day 533 No response (n=118, n=121, n=92)
|
3.4 percentage of participants
|
8.3 percentage of participants
|
10.9 percentage of participants
|
|
OL; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Over Time
Day 533 Moderate response (n=118, n=121, n=92)
|
58.5 percentage of participants
|
58.7 percentage of participants
|
53.3 percentage of participants
|
|
OL; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Over Time
Day 729 Good response (n=110, n=121, n=93)
|
41.8 percentage of participants
|
45.5 percentage of participants
|
34.4 percentage of participants
|
|
OL; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Over Time
Day 729 Moderate response (n=110, n=121, n=93)
|
53.6 percentage of participants
|
47.9 percentage of participants
|
51.6 percentage of participants
|
|
OL; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Over Time
Day 729 No response (n=110, n=121, n=93)
|
4.5 percentage of participants
|
6.6 percentage of participants
|
14.0 percentage of participants
|
|
OL; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Over Time
Day 533 Good response (n=118, n=121, n=92)
|
38.1 percentage of participants
|
33.1 percentage of participants
|
35.9 percentage of participants
|
SECONDARY outcome
Timeframe: DB Day 197, Day 365, Day 533, Day 729Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period. n=number of participants with data available.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=132 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=136 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=104 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time
Day 365, ACR 50 (n=131, n=136, n=102)
|
55.0 percentage of participants
|
43.4 percentage of participants
|
54.9 percentage of participants
|
|
OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time
Day 197, ACR 20 (n=130, n=133, n=102)
|
73.1 percentage of participants
|
68.4 percentage of participants
|
44.1 percentage of participants
|
|
OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time
Day 197, ACR 50 (n=129, n=134, n=103)
|
45.7 percentage of participants
|
42.5 percentage of participants
|
21.4 percentage of participants
|
|
OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time
Day 533, ACR 20 (n=128, n=128, n=102)
|
82.8 percentage of participants
|
82.8 percentage of participants
|
74.5 percentage of participants
|
|
OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time
Day 533, ACR 50 (n=129, n=128, n=103)
|
58.1 percentage of participants
|
57.0 percentage of participants
|
47.6 percentage of participants
|
|
OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time
Day 533, ACR 70 (n=129, n=127, n=102)
|
35.7 percentage of participants
|
40.9 percentage of participants
|
32.4 percentage of participants
|
|
OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time
Day 729, ACR 20 (n=119, n=127, n=102)
|
86.6 percentage of participants
|
84.3 percentage of participants
|
76.5 percentage of participants
|
|
OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time
Day 729, ACR 50 (n=117, n=127, n=101)
|
60.7 percentage of participants
|
70.9 percentage of participants
|
49.5 percentage of participants
|
|
OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time
Day 729, ACR 70 (n=120, n=127, n=100)
|
40.8 percentage of participants
|
44.9 percentage of participants
|
33.0 percentage of participants
|
|
OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time
Day 197, ACR 70 (n=130, n=133, n=103)
|
23.1 percentage of participants
|
27.1 percentage of participants
|
10.7 percentage of participants
|
|
OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time
Day 365, ACR 20 (n=130, n=136, n=103)
|
88.5 percentage of participants
|
69.1 percentage of participants
|
75.7 percentage of participants
|
|
OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time
Day 365, ACR 70 (n=131, n=136, n=102)
|
31.3 percentage of participants
|
23.5 percentage of participants
|
31.4 percentage of participants
|
SECONDARY outcome
Timeframe: Defined from the date of achieving ACR 70 response to 6 months post responsePopulation: Protocol-specified analyses of the proportion of participants achieving a Major Clinical Response were not performed since ACR responses in the open-label period could only be assessed at 6-month intervals due to the fact that CRP and ESR were only measured every 6 months during this period.
Major Clinical Response was defined as a continuous ACR 70 for six months.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: OL Days 197, 253, 281, 309, 337, 365, 449, 533, 617, and 729Population: Number of Participants Analyzed=All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period.n=number of participants with data available.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=132 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=136 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=104 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time
Day 729 (n=122, n=127, n=103)
|
74.6 percentage of participants
|
78.0 percentage of participants
|
63.1 percentage of participants
|
|
OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time
Day 197 (n=131, n=134, n=103)
|
70.2 percentage of participants
|
68.7 percentage of participants
|
42.7 percentage of participants
|
|
OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time
Day 225 (n=132, n=133, n=101)
|
75.0 percentage of participants
|
72.9 percentage of participants
|
52.5 percentage of participants
|
|
OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time
Day 449 (n=129, n=133, n=101)
|
70.5 percentage of participants
|
72.9 percentage of participants
|
64.4 percentage of participants
|
|
OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time
Day 253 (n=130, n=135, n=102)
|
71.5 percentage of participants
|
65.2 percentage of participants
|
57.8 percentage of participants
|
|
OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time
Day 309 (n=131, n=134, n=102)
|
71.0 percentage of participants
|
70.1 percentage of participants
|
62.7 percentage of participants
|
|
OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time
Day 533 (n=128, n=127, n=103)
|
74.2 percentage of participants
|
78.0 percentage of participants
|
61.2 percentage of participants
|
|
OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time
Day 337 (n=130, n=136, n=101)
|
71.5 percentage of participants
|
72.1 percentage of participants
|
63.4 percentage of participants
|
|
OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time
Day 281 (n=131, n=135, n=102)
|
73.3 percentage of participants
|
71.9 percentage of participants
|
52.0 percentage of participants
|
|
OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time
Day 365 (n=130, n=136, n=103)
|
70.8 percentage of participants
|
67.6 percentage of participants
|
61.2 percentage of participants
|
|
OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time
Day 617 (n=123, n=127, n=103)
|
78.9 percentage of participants
|
79.5 percentage of participants
|
64.1 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Day 729Population: All Treated Population, all participants who entered the open-label period and received at least one dose of abatacept at any time during this period. Treatment groups represent treatment received in the DB period.
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.
Outcome measures
| Measure |
ABA + MTX [DB]
n=122 Participants
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=127 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
PLA + MTX [DB]
n=103 Participants
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly)
|
|---|---|---|---|
|
OL; Adjusted Mean Change From Baseline to Day 729 in HAQ-DI
HAQ-DI
|
-0.83 units on a scale
Standard Error 0.06
|
-0.84 units on a scale
Standard Error 0.06
|
-0.64 units on a scale
Standard Error 0.07
|
|
OL; Adjusted Mean Change From Baseline to Day 729 in HAQ-DI
HAQ-DI component: dressing and grooming
|
-0.93 units on a scale
Standard Error 0.08
|
-91.0 units on a scale
Standard Error 0.08
|
-0.68 units on a scale
Standard Error 0.09
|
|
OL; Adjusted Mean Change From Baseline to Day 729 in HAQ-DI
HAQ-DI component: arising
|
-0.8 units on a scale
Standard Error 0.09
|
-0.77 units on a scale
Standard Error 0.08
|
-0.72 units on a scale
Standard Error 0.09
|
|
OL; Adjusted Mean Change From Baseline to Day 729 in HAQ-DI
HAQ-DI component: hygiene
|
-0.65 units on a scale
Standard Error 0.10
|
-0.65 units on a scale
Standard Error 0.08
|
-0.5 units on a scale
Standard Error 0.09
|
|
OL; Adjusted Mean Change From Baseline to Day 729 in HAQ-DI
HAQ-DI component: eating
|
-0.86 units on a scale
Standard Error 0.09
|
-0.99 units on a scale
Standard Error 0.09
|
-0.82 units on a scale
Standard Error 0.10
|
|
OL; Adjusted Mean Change From Baseline to Day 729 in HAQ-DI
HAQ-DI component: walking
|
-0.78 units on a scale
Standard Error 0.09
|
-0.73 units on a scale
Standard Error 0.08
|
-0.54 units on a scale
Standard Error 0.08
|
|
OL; Adjusted Mean Change From Baseline to Day 729 in HAQ-DI
HAQ-DI component: activities
|
-0.75 units on a scale
Standard Error 0.09
|
-0.73 units on a scale
Standard Error 0.09
|
-0.61 units on a scale
Standard Error 0.09
|
|
OL; Adjusted Mean Change From Baseline to Day 729 in HAQ-DI
HAQ-DI component: reach
|
-0.97 units on a scale
Standard Error 0.09
|
-0.94 units on a scale
Standard Error 0.10
|
-0.64 units on a scale
Standard Error 0.09
|
|
OL; Adjusted Mean Change From Baseline to Day 729 in HAQ-DI
HAQ-DI component: grip
|
-0.88 units on a scale
Standard Error 0.09
|
-0.96 units on a scale
Standard Error 0.09
|
-0.61 units on a scale
Standard Error 0.09
|
Adverse Events
ABA (DB)
ABA + MTX [OL]
INF + MTX [DB]
PLA + MTX [DB]
Serious adverse events
| Measure |
ABA (DB)
n=156 participants at risk
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
ABA + MTX [OL]
n=372 participants at risk
All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
|
INF + MTX [DB]
n=165 participants at risk
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=110 participants at risk
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, 104 participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
|
|---|---|---|---|---|
|
Injury, poisoning and procedural complications
COMPLICATED FRACTURE
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
ROAD TRAFFIC ACCIDENT
|
0.64%
1/156
|
0.00%
0/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
LUMBAR VERTEBRAL FRACTURE
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
POST PROCEDURAL HAEMATOMA
|
0.64%
1/156
|
0.00%
0/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Eye disorders
CATARACT
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Eye disorders
CORNEAL PERFORATION
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Investigations
HORMONE LEVEL ABNORMAL
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Cardiac disorders
ARRHYTHMIA
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Cardiac disorders
PERICARDITIS
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Cardiac disorders
ANGINA PECTORIS
|
0.64%
1/156
|
0.27%
1/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Cardiac disorders
ANGINA UNSTABLE
|
0.64%
1/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Cardiac disorders
CARDIAC FAILURE
|
0.00%
0/156
|
0.27%
1/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Cardiac disorders
ATRIAL TACHYCARDIA
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
0.00%
0/156
|
0.81%
3/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Cardiac disorders
CORONARY ARTERY DISEASE
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Cardiac disorders
CORONARY ARTERY OCCLUSION
|
0.64%
1/156
|
0.00%
0/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION
|
0.00%
0/156
|
0.54%
2/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Vascular disorders
ARTERITIS
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Vascular disorders
HAEMATOMA
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Vascular disorders
VASCULITIS
|
0.64%
1/156
|
0.00%
0/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Vascular disorders
HYPERTENSION
|
0.00%
0/156
|
0.27%
1/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Vascular disorders
AORTIC STENOSIS
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Vascular disorders
HYPERTENSIVE CRISIS
|
0.64%
1/156
|
0.00%
0/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Endocrine disorders
ADRENAL INSUFFICIENCY
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Psychiatric disorders
DEPRESSION
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Hepatobiliary disorders
BILIARY COLIC
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Hepatobiliary disorders
CHOLELITHIASIS
|
0.64%
1/156
|
0.54%
2/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Immune system disorders
ANAPHYLACTIC SHOCK
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Nervous system disorders
SCIATICA
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Nervous system disorders
CEREBROVASCULAR ACCIDENT
|
0.64%
1/156
|
0.00%
0/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Gastrointestinal disorders
GASTRITIS
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Gastrointestinal disorders
ANAL FISSURE
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Gastrointestinal disorders
ANAL SKIN TAGS
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Gastrointestinal disorders
INGUINAL HERNIA
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Gastrointestinal disorders
UMBILICAL HERNIA
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Gastrointestinal disorders
PANCREATITIS ACUTE
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Gastrointestinal disorders
HYPERTROPHIC ANAL PAPILLA
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Gastrointestinal disorders
UPPER GASTROINTESTINAL HAEMORRHAGE
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Ear and labyrinth disorders
VERTIGO
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Infections and infestations
SEPSIS
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Infections and infestations
ABSCESS
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Infections and infestations
PNEUMONIA
|
1.3%
2/156
|
0.27%
1/372
|
1.8%
3/165
|
0.91%
1/110
|
|
Infections and infestations
SINUSITIS
|
0.64%
1/156
|
0.00%
0/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Infections and infestations
BRONCHITIS
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Infections and infestations
CELLULITIS
|
0.00%
0/156
|
0.81%
3/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Infections and infestations
ERYSIPELAS
|
0.00%
0/156
|
0.27%
1/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Infections and infestations
APPENDICITIS
|
0.00%
0/156
|
0.54%
2/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Infections and infestations
SEPTIC SHOCK
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Infections and infestations
HERPES ZOSTER
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Infections and infestations
OSTEOMYELITIS
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Infections and infestations
GASTROENTERITIS
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Infections and infestations
LOBAR PNEUMONIA
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Infections and infestations
WOUND INFECTION
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Infections and infestations
BURSITIS INFECTIVE
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Infections and infestations
ABSCESS SOFT TISSUE
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Infections and infestations
ENCEPHALITIS HERPES
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Infections and infestations
INFECTED SKIN ULCER
|
0.64%
1/156
|
0.00%
0/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Infections and infestations
SUBCUTANEOUS ABSCESS
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Infections and infestations
NECROTISING FASCIITIS
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Infections and infestations
PULMONARY TUBERCULOSIS
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Infections and infestations
APPENDICITIS PERFORATED
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Infections and infestations
PERITONEAL TUBERCULOSIS
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.00%
0/156
|
1.3%
5/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Infections and infestations
LUNG INFECTION PSEUDOMONAL
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Infections and infestations
POSTOPERATIVE WOUND INFECTION
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.91%
1/110
|
|
Infections and infestations
PNEUMOCYSTIS JIROVECI PNEUMONIA
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Renal and urinary disorders
RENAL FAILURE
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Renal and urinary disorders
BLADDER PROLAPSE
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Renal and urinary disorders
RENAL IMPAIRMENT
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Renal and urinary disorders
STRESS URINARY INCONTINENCE
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Metabolism and nutrition disorders
HYPOGLYCAEMIA
|
0.64%
1/156
|
0.00%
0/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Metabolism and nutrition disorders
DIABETES MELLITUS
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Blood and lymphatic system disorders
ANAEMIA
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
0.64%
1/156
|
0.00%
0/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Skin and subcutaneous tissue disorders
PSORIASIS
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Skin and subcutaneous tissue disorders
URTICARIA
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Reproductive system and breast disorders
OVARIAN CYST
|
0.00%
0/156
|
0.54%
2/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Reproductive system and breast disorders
DYSMENORRHOEA
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Reproductive system and breast disorders
UTERINE POLYP
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Reproductive system and breast disorders
OVARIAN TORSION
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Reproductive system and breast disorders
UTERINE PROLAPSE
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
FALL
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
ACCIDENT
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
HIP FRACTURE
|
0.64%
1/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
ANKLE FRACTURE
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Injury, poisoning and procedural complications
ILIUM FRACTURE
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
TENDON RUPTURE
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
TIBIA FRACTURE
|
0.64%
1/156
|
0.00%
0/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
CARTILAGE INJURY
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
MULTIPLE INJURIES
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
FAILURE OF IMPLANT
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Injury, poisoning and procedural complications
SUBDURAL HAEMATOMA
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
ACCIDENTAL OVERDOSE
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
LOWER LIMB FRACTURE
|
0.00%
0/156
|
0.27%
1/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
PUBIC RAMI FRACTURE
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
UPPER LIMB FRACTURE
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
CERVICAL VERTEBRAL FRACTURE
|
0.64%
1/156
|
0.00%
0/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
POST PROCEDURAL COMPLICATION
|
0.00%
0/156
|
0.54%
2/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Injury, poisoning and procedural complications
DISLOCATION OF JOINT PROSTHESIS
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Musculoskeletal and connective tissue disorders
FISTULA
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Musculoskeletal and connective tissue disorders
ARTHRITIS
|
0.00%
0/156
|
1.1%
4/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Musculoskeletal and connective tissue disorders
OSTEONECROSIS
|
0.64%
1/156
|
0.54%
2/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Musculoskeletal and connective tissue disorders
FOOT DEFORMITY
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Musculoskeletal and connective tissue disorders
JOINT SWELLING
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS
|
0.64%
1/156
|
1.1%
4/372
|
0.00%
0/165
|
1.8%
2/110
|
|
Musculoskeletal and connective tissue disorders
RHEUMATOID ARTHRITIS
|
0.64%
1/156
|
5.1%
19/372
|
2.4%
4/165
|
3.6%
4/110
|
|
Musculoskeletal and connective tissue disorders
SPINAL OSTEOARTHRITIS
|
0.64%
1/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Musculoskeletal and connective tissue disorders
LUMBAR SPINAL STENOSIS
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAIN
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Musculoskeletal and connective tissue disorders
INTERVERTEBRAL DISC PROTRUSION
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOTHORAX
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Respiratory, thoracic and mediastinal disorders
LARYNGEAL OEDEMA
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Respiratory, thoracic and mediastinal disorders
LARYNGEAL GRANULOMA
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
0.00%
0/156
|
0.27%
1/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Respiratory, thoracic and mediastinal disorders
SLEEP APNOEA SYNDROME
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Respiratory, thoracic and mediastinal disorders
OBSTRUCTIVE AIRWAYS DISORDER
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
General disorders
PYREXIA
|
0.64%
1/156
|
0.54%
2/372
|
0.00%
0/165
|
0.00%
0/110
|
|
General disorders
HYPERTHERMIA
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LEIOMYOMA
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
FIBROSARCOMA
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BLADDER CANCER
|
0.64%
1/156
|
0.00%
0/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
UTERINE LEIOMYOMA
|
0.64%
1/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.91%
1/110
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BENIGN LUNG NEOPLASM
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PITUITARY TUMOUR BENIGN
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SQUAMOUS CELL CARCINOMA
|
0.00%
0/156
|
0.27%
1/372
|
0.00%
0/165
|
0.00%
0/110
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT ANORECTAL NEOPLASM
|
0.00%
0/156
|
0.00%
0/372
|
0.61%
1/165
|
0.00%
0/110
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BENIGN NEOPLASM OF THYROID GLAND
|
0.00%
0/156
|
0.00%
0/372
|
0.00%
0/165
|
0.91%
1/110
|
Other adverse events
| Measure |
ABA (DB)
n=156 participants at risk
Abatacept was administered intravenously (IV) on Days 1, 15, 29 and every 28 days thereafter for a total of 14 doses. Administration was as follows: 500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 gram for participants \> 100 kg. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
ABA + MTX [OL]
n=372 participants at risk
All participants received ABA at a weight-tiered dose of 10 mg/kg plus a stable dose of MTX (minimum 15 mg weekly).
|
INF + MTX [DB]
n=165 participants at risk
Infliximab was given 3 mg/kg IV (approved labeled dose) on Days 1, 15, 43, 85 and every 56 days thereafter for a total of 8 doses. All participants received a stable dose of MTX (minimum 15 mg weekly).
|
PLA + MTX [DB]
n=110 participants at risk
Normal saline was administered as placebo. All participants received a stable dose of MTX (minimum 15 mg weekly). After placebo treatment from Day 1-197, 104 participants were reallocated to receive abatacept (weight based) plus a stable dose of MTX (minimum 15 mg weekly).
|
|---|---|---|---|---|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
3.8%
6/156
|
2.4%
9/372
|
2.4%
4/165
|
5.5%
6/110
|
|
Vascular disorders
HYPERTENSION
|
8.3%
13/156
|
11.3%
42/372
|
6.7%
11/165
|
11.8%
13/110
|
|
Psychiatric disorders
ANXIETY
|
3.2%
5/156
|
6.5%
24/372
|
4.2%
7/165
|
1.8%
2/110
|
|
Psychiatric disorders
INSOMNIA
|
3.2%
5/156
|
4.0%
15/372
|
7.3%
12/165
|
2.7%
3/110
|
|
Psychiatric disorders
DEPRESSION
|
3.8%
6/156
|
7.0%
26/372
|
3.6%
6/165
|
0.91%
1/110
|
|
Nervous system disorders
HEADACHE
|
14.7%
23/156
|
14.5%
54/372
|
20.6%
34/165
|
21.8%
24/110
|
|
Nervous system disorders
DIZZINESS
|
7.1%
11/156
|
6.7%
25/372
|
7.9%
13/165
|
6.4%
7/110
|
|
Gastrointestinal disorders
NAUSEA
|
10.3%
16/156
|
7.0%
26/372
|
12.7%
21/165
|
9.1%
10/110
|
|
Gastrointestinal disorders
VOMITING
|
3.2%
5/156
|
3.5%
13/372
|
6.1%
10/165
|
4.5%
5/110
|
|
Gastrointestinal disorders
DIARRHOEA
|
13.5%
21/156
|
15.1%
56/372
|
12.7%
21/165
|
6.4%
7/110
|
|
Gastrointestinal disorders
DYSPEPSIA
|
12.2%
19/156
|
11.0%
41/372
|
10.3%
17/165
|
6.4%
7/110
|
|
Gastrointestinal disorders
GASTRITIS
|
3.8%
6/156
|
5.9%
22/372
|
4.8%
8/165
|
6.4%
7/110
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
1.9%
3/156
|
6.2%
23/372
|
4.8%
8/165
|
1.8%
2/110
|
|
Infections and infestations
INFLUENZA
|
8.3%
13/156
|
13.2%
49/372
|
7.3%
12/165
|
5.5%
6/110
|
|
Infections and infestations
SINUSITIS
|
6.4%
10/156
|
7.8%
29/372
|
4.2%
7/165
|
7.3%
8/110
|
|
Infections and infestations
BRONCHITIS
|
7.1%
11/156
|
11.0%
41/372
|
6.1%
10/165
|
10.0%
11/110
|
|
Infections and infestations
PHARYNGITIS
|
7.7%
12/156
|
11.6%
43/372
|
10.3%
17/165
|
8.2%
9/110
|
|
Infections and infestations
GASTROENTERITIS
|
2.6%
4/156
|
6.2%
23/372
|
7.3%
12/165
|
5.5%
6/110
|
|
Infections and infestations
NASOPHARYNGITIS
|
12.8%
20/156
|
18.5%
69/372
|
15.8%
26/165
|
13.6%
15/110
|
|
Infections and infestations
URINARY TRACT INFECTION
|
5.1%
8/156
|
18.0%
67/372
|
10.9%
18/165
|
11.8%
13/110
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
7.1%
11/156
|
13.4%
50/372
|
11.5%
19/165
|
14.5%
16/110
|
|
Skin and subcutaneous tissue disorders
RASH
|
0.64%
1/156
|
3.2%
12/372
|
6.1%
10/165
|
0.91%
1/110
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
3.2%
5/156
|
1.3%
5/372
|
6.1%
10/165
|
0.91%
1/110
|
|
Skin and subcutaneous tissue disorders
URTICARIA
|
1.9%
3/156
|
2.7%
10/372
|
6.7%
11/165
|
2.7%
3/110
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
7.7%
12/156
|
11.0%
41/372
|
6.1%
10/165
|
7.3%
8/110
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
3.8%
6/156
|
7.5%
28/372
|
4.2%
7/165
|
4.5%
5/110
|
|
General disorders
OEDEMA PERIPHERAL
|
5.1%
8/156
|
4.8%
18/372
|
3.6%
6/165
|
4.5%
5/110
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER