Phase 3
Completed N=431
Abatacept and Infliximab in Combination With Methotrexate in Subjects With Rheumatoid Arthritis
Source: ClinicalTrials.gov NCT00095147 ↗Enrolled (actual)
431
Serious AEs
19.7%
Results posted
Jan 2011
Primary outcomePrimary: 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; -1.48 units on a scale — p=<0.001
Summary
The purpose of this clinical research study is to learn if Abatacept or Infliximab in combination with Methotrexate demonstrate a greater reduction in disease activity over placebo.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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; -1.48 | <0.001 sig |
| PRIMARY 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 |
3; 90; 12; 5; 349; 165 | — |
| PRIMARY OL; Number of Participants With AEs of Special Interest |
277; 3; 18; 13; 50; 28 | — |
| PRIMARY OL; Number of Participants With Select Hematologic Laboratory Abnormalities |
9; 7; 6; 2; 29; 1 | — |
| PRIMARY OL; Number of Participants With Select Blood Chemistry Laboratory Abnormalities |
1; 4; 11; 16; 1; 17 | — |
| PRIMARY OL; Mean Change From Baseline to Day 365 in Hemoglobin, Total Protein, and Albumin |
0.53; 0.24; 0.43; -0.09; 0.11; -0.12 | — |
| PRIMARY OL; Mean Change From Baseline to Day 365 in Platelets |
-42.4; -35.5; -28.4 | — |
| PRIMARY OL; Mean Change From Baseline to Day 365 in Hematocrit |
1.44; 0.51; 1.03 | — |
| PRIMARY OL; Mean Change From Baseline to Day 365 in White Blood Cells |
-0.95; -0.90; -0.84; -0.91; -1.14; -1.05 | — |
| PRIMARY OL; Mean Change From Baseline to Day 365 in Erythrocytes |
0.09; 0.00; 0.006 | — |
| PRIMARY OL; Mean Change From Baseline to Day 365 in Electrolytes |
-1.62; -1.57; -1.09; -0.03; -0.07; -0.03 | — |
| PRIMARY OL; Mean Change From Baseline to Day 365 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid |
0.03; 0.02; 0.01; -0.31; -0.52; 0.10 | — |
| PRIMARY OL; Mean Change From Baseline to Day 365 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase |
3.51; 2.19; -0.04; 0.54; -0.11; -2.23 | — |
| PRIMARY OL; Mean Change From Baseline to Day 729 in Hemoglobin, Total Protein, and Albumin |
0.66; 0.48; 0.40; -0.33; -0.25; -0.29 | — |
| PRIMARY OL; Mean Change From Baseline to Day 729 in Platelets |
-63.9; -5832; -47.7 | — |
| PRIMARY OL; Mean Change From Baseline to Day 729 in Hematocrit |
1.72; 1.23; 0.99 | — |
| PRIMARY OL; Mean Change From Baseline to Day 729 in White Blood Cells |
-1.57; -1.23; -1.28; -1.62; -1.35; -1.33 | — |
| PRIMARY OL; Mean Change From Baseline to Day 729 in Erythrocytes |
0.07; 0.04; 0.02 | — |
| PRIMARY OL; Mean Change From Baseline to Day 729 in Electrolytes |
-1.10; -1.12; -1.22; -0.03; -0.04; -0.02 | — |
| PRIMARY OL; Mean Change From Baseline to Day 729 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid |
0.08; 0.08; 0.07; -0.37; -0.12; 0.20 | — |
| PRIMARY OL; Mean Change From Baseline to Day 729 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase |
2.73; 1.02; -0.89; 0.03; -0.22; -2.45 | — |
| PRIMARY OL; Mean Change From Baseline to Day 1121 in Hemoglobin, Total Protein, and Albumin |
0.66; 0.53; 0.57; -0.35; -0.24; -0.33 | — |
| PRIMARY OL; Mean Change From Baseline to Day 1121 in Platelets |
-67.5; -66.1; -62.5 | — |
| PRIMARY OL; Mean Change From Baseline to Day 1121 in Hematocrit |
1.83; 1.50; 1.47 | — |
| PRIMARY OL; Mean Change From Baseline to Day 1121 in White Blood Cells |
-1.07; -1.09; -0.99; -1.17; -1.40; -1.28 | — |
| PRIMARY OL; Mean Change From Baseline to Day 1121 in Erythrocytes |
0.11; 0.11; 0.12 | — |
| PRIMARY OL; Mean Change From Baseline to Day 1121 in Electrolytes |
-1.80; -1.38; -1.34; 0.01; 0.08; 0.01 | — |
| PRIMARY OL; Mean Change From Baseline to Day 1121 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid |
0.06; 0.07; 0.08; -0.04; 0.34; 0.20 | — |
| PRIMARY OL; Mean Change From Baseline to Day 1121 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase |
4.74; 4.66; -0.35; 3.79; 4.49; 0.38 | — |
| PRIMARY OL; Mean Change From Baseline to Day 1513 in Hemoglobin, Total Protein, and Albumin |
0.25; 0.44; 0.56; -0.73; -0.33; -0.34 | — |
| PRIMARY OL; Mean Change From Baseline to Day 1513 in Platelets |
-78.0; -74.0; -99.2 | — |
| PRIMARY OL; Mean Change From Baseline to Day 1513 in Hematocrit |
0.92; 1.28; 1.18 | — |
| PRIMARY OL; Mean Change From Baseline to Day 1513 in White Blood Cells |
-0.34; -1.08; -2.13; -0.37; -1.03; -1.93 | — |
| PRIMARY OL; Mean Change From Baseline to Day 1513 in Erythrocytes |
-0.10; 0.00; -0.09 | — |
| PRIMARY OL; Mean Change From Baseline to Day 1513 in Electrolytes |
-4.36; -3.80; -4.50; -0.16; -0.32; -0.46 | — |
| PRIMARY OL; Mean Change From Baseline to Day 1513 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid |
0.10; 0.05; 0.08; 2.87; -0.40; 0.63 | — |
| PRIMARY OL; Mean Change From Baseline to Day 1513 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase |
-1.87; -9.20; 2.44; -1.35; -2.85; 0.38 | — |
| PRIMARY OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period |
119.0; 118.8; 120.4; 119.5; 121.1; 119.2 | — |
| PRIMARY OL; Mean Heart Rate (HR) During Open Label Period |
74.2; 74.1; 74.2; 73.4; 73.9; 73.8 | — |
| PRIMARY OL; Mean Temperature (T) During Open Label Period |
36.3; 36.3; 36.3; 36.3; 36.2; 36.2 | — |
| SECONDARY DB; Adjusted Mean Change From Baseline to Day 197 in DAS 28 Score (ESR) For INF Versus PLA (LOCF Analysis) |
-2.25; -1.48 | <0.001 sig |
| SECONDARY DB; DAS 28 (ESR) Area Under The Curve (AUC) Over 12 Months For ABA Versus INF |
1638.6; 1657.5 | — |
| SECONDARY DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 197 |
61.5; 58.8; 40.9 | 0.001 sig |
| SECONDARY DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 365 |
57.7; 52.7; 57.3 | — |
| SECONDARY DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis) |
-0.69; -0.61; -0.31; -0.61; -0.54; -0.22 | <0.001 sig |
| SECONDARY DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis) |
-0.67; -0.59; -0.56; -0.55; -0.52; -0.55 | — |
| SECONDARY DB; Adjusted Mean Change From Baseline to Day 197 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) |
8.36; 7.66; 4.34; 5.14; 4.32; 1.64 | <0.001 sig |
| SECONDARY DB; Adjusted Mean Change From Baseline to Day 365 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) |
9.52; 7.59; 8.00; 5.96; 4.03; 5.85 | — |
| SECONDARY DB; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) at Day 365 |
27.3; 36.3; 23.5; 40.7; 45.2; 49.0 | — |
| SECONDARY DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 197 |
66.7; 59.4; 41.8; 40.4; 37.0; 20.0 | — |
| SECONDARY DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 365 |
72.4; 55.8; 68.2; 45.5; 36.4; 50.9 | — |
| SECONDARY 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 |
1; 1; 0; 8; 19; 13 | — |
| SECONDARY DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 197 |
12; 18; 8; 1; 2; 1 | — |
| SECONDARY 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 |
1; 2; 15; 30; 5; 14 | — |
| SECONDARY 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 |
1; 12; 3; 0; 71; 26 | — |
| SECONDARY DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 365 |
16; 30; 1; 2; 2; 1 | — |
| SECONDARY DB; Number of Participants With AEs of Special Interest From Day 198 Through Day 365 in Participants Receiving Placebo Switched to Abatacept |
3; 1; 5 | — |
| SECONDARY DB; Number of Participants With Significant Changes in Mean Systolic and Diastolic Blood Pressure During Days 1 Through 197 and Days 1 Through 365 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY DB; Number of Participants With Significant Changes in Mean Heart Rate During Days 1 Through 197 and Days 1 Through 365 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY DB; Number of Participants With Significant Changes in Mean Temperature During Days 1 Through 197 and Days 1 Through 365 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197 |
1; 1; 1; 0; 2; 0 | — |
| SECONDARY DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365 |
2; 1; 1; 1; 2; 0 | — |
| SECONDARY DB; Number of Participants With Anti-Abatacept Antibodies From Day 1 Through Day 365 (Electrochemiluminescent [ECL] Immunoassay) |
0; 0; 0; 0 | — |
| SECONDARY DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365 |
62.0; 73.0; 0; 3.7; 20.0; 74.7 | — |
| SECONDARY OL; Mean Change From Baseline Over Time in DAS 28 (ESR) Score |
-3.12; -2.39; -2.81; -3.21; -3.04; -2.84 | — |
| SECONDARY OL; Percentage of Participants With DAS28 (ESR) Remission and Low Disease Activity (LDAS) Over Time |
19.7; 13.3; 15.7; 37.0; 23.0; 29.4 | — |
| SECONDARY OL; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Over Time |
38.5; 23.1; 30.9; 53.3; 58.5; 55.3 | — |
| SECONDARY OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time |
73.1; 68.4; 44.1; 45.7; 42.5; 21.4 | — |
| SECONDARY OL; Percentage of Participants Who Achieved Major Clinical Response |
— | — |
| SECONDARY OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time |
70.2; 68.7; 42.7; 75.0; 72.9; 52.5 | — |
| SECONDARY OL; Adjusted Mean Change From Baseline to Day 729 in HAQ-DI |
-0.83; -0.84; -0.64; -0.93; -91.0; -0.68 | — |
Eligibility Criteria
Inclusion Criteria
- Diagnosis of Rheumatoid Arthritis
- At least 3 months prior treatment with Methotrexate (MTX)
- At least 10 swollen joints and 12 tender joints and C-Reactive Protein of at least 1 mg/dl
- Washout required for other disease modifying anti-rheumatic drugs (DMARDS)
Exclusion Criteria
- participants who have failed more than 3 DMARDs
- participants previously treated with an approved biologic drug
- History of cancer in the last 5 years
- Severe or recurrent bacterial infection
- Any previous or current medical conditions that are contraindications to the use of TNF blocking agents
- Women of Child Bearing Potential
Data sourced from ClinicalTrials.gov (NCT00095147). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.