Please select the outcome measures that correspond to the clinical trial below.
Title: A Randomized, Double-blind Study of Safety and Prevention of Structural Joint Damage During Treatment With Tocilizumab Versus Placebo, in Combination With Methotrexate, in Patients With Moderate to Severe Rheumatoid Arthritis
Brief Summary: This 3 arm study will compare the safety and efficacy, with respect to a reduction in signs and symptoms and prevention of joint damage, of tocilizumab versus placebo, both in combination with methotrexate (MTX) in patients with moderate to severe active rheumatoid arthritis. Patients will be randomized to receive tocilizumab 4 mg/kg IV, tocilizumab 8 mg/kg IV or placebo IV, every 4 weeks. All patients will also receive methotrexate, 10-25 mg/week. The anticipated time on study treatment is 1-2 years and the target sample size is 500+ individuals. After completion of the 2 year study participants could participate in the optional 3 year open label extension phase (year 3 to 5).


Options:
A: Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 6 (Week 6)
B: Number of American College of Rheumatology 20 (ACR 20) Responders at Day 169 (Day 169); Number of Participants Achieving Clinically Meaningful Improvement in Health Assessment Questionnaire (HAQ) at Day 365 (Day 365); Baseline and Mean Change From Baseline (BL) in Radiographic Erosion Score Results at Day 365 (BL (Day 0), Day 365); Participants With Deaths, Adverse Events (AEs) and SAEs in the Open-Label (OL) Period (Day 365 to Day 2,185); Participants With Hematology Values Meeting the Marked Abnormality Criteria in the OL Period (Day 365 to Day 2,185); Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria in the OL Period (Day 365 to Day 2,185); Participants With Electrolyte Values Meeting the Marked Abnormality Criteria in the OL Period (Day 365 to Day 2,185); Participants With Glucose, Protein, Metabolites, and Urinalysis Values Meeting the Marked Abnormality Criteria in the OL Period (Day 365 to Day 2,185); Mean BL Immunoglobulins Over Time in the OL Period (BL (Day 0), Day 365, Day 729, Day 1,093); Mean Change From BL in Immunoglobulins in the OL Period (BL (Day 0), Day 365, Day 729, Day 1,093); Participants With Immunogenicity to Abatacept in the Cumulative DB + OL Period (Day 1 to Day 1,821); Number of Participants Experiencing Clinically Significant Changes in Vital Signs in the OL Period (Day 365 to Day 1,821. All changes in participant vital signs were monitored on each day of study drug administration prior to dosing and 60 minutes after dosing.); Number of Participants Experiencing AEs of Special Interest in the OL Period (Day 365 to Day 2,185); Mean BL Hematocrit in the OL Period (Baseline (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185); Mean Change From BL in Participant Hematocrit in the OL Period (BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185); Mean BL Platelet Count in the OL Period (BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185); Mean Change From BL in Participant Platelet Count in the OL Period (BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185); Mean BL Hemoglobin, Total Protein, and Albumin in the OL Period (BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185); Mean Change From BL in Hemoglobin, Total Protein, and Albumin in the OL Period (BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185); Mean BL White Blood Cells in the OL Period (BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185); Mean Change From BL in White Blood Cells in the OL Period (BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185); Mean BL Liver Function Parameters in the OL Period (BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185); Mean Change From BL in Liver Function Parameters in the OL Period (BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185); Mean BL Select Laboratory Parameters in the OL Period (BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185); Mean Change From BL in Select Laboratory Parameters in the OL Period (BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185); Mean BL Serum Electrolytes in the OL Period (BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185); Mean Change From BL in Serum Electrolytes in the OL Period (BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185)
C: Change From Baseline in Synovial Tissue Messenger Ribonucleic Acid (mRNA) Expression at Day 28 (Day -7 (Baseline), Day 28); Change From Baseline in Protein Expression of Tumor Necrosis Factor Alpha (TNFalpha), Interleukin-6 (IL-6), Interleukin-17a (IL-17a) and Interleukin-10 (IL-10) at Day 28 (Baseline (Day -7), Day 28); Change From Baseline in Percentage of Area Stained For CD3+ and CD68+ Surface Markers of Inflammatory Cells of the Synovial Tissue at Day 28 (Baseline (Day -7), Day 28); Blood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at Baseline (Day-7) (Baseline (Day -7)); Blood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at Day 28 (Day 28); Blood Cytokine Level at Pre-dose on Day 1 (Pre-dose on Day 1); Blood Cytokine Level at 1 Hour Post-dose on Day 1 (1 hour post-dose on Day 1); Blood Cytokine Level at 4 Hours Post-dose on Day 1 (4 hours post-dose on Day 1); Blood Cytokine Level at Pre-dose on Day 10 (Pre-dose on Day 10); Blood Cytokine Level at Pre-dose on Day 28 (Pre-dose on Day 28); Blood Cytokine Level at 1 Hour Post-dose on Day 28 (1 Hour Post-dose on Day 28); Blood Cytokine Level at 4 Hours Post-dose on Day 28 (4 Hours Post-dose on Day 28); Blood Cytokine Level at 8 Hours Post-dose on Day 28 (8 Hours Post-dose on Day 28); Blood Cytokine Level at 24 Hours Post-dose on Day 28 (24 Hours Post-dose on Day 28); Blood Cytokine Level at Pre-dose on Day 35 or Early Termination (Pre-dose on Day 35 or Early Termination); Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 1 (Pre-dose on Day 1); Blood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 1 (1 Hour Post-dose on Day 1); Blood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 1 (4 Hours Post-dose on Day 1); Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 10 (Pre-dose on Day 10); Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 28 (Pre-dose on Day 28); Blood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 28 (1 Hour Post-dose on Day 28); Blood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 28 (4 Hours Post-dose on Day 28); Blood T, B and NK Lymphocyte Counts at 8 Hours Post-dose on Day 28 (8 Hours Post-dose on Day 28); Blood T, B and NK Lymphocyte Counts at 24 Hours Post-dose on Day 28 (24 Hours Post-dose on Day 28); Blood T, B and NK Lymphocyte Counts and Possible Subsets at Pre-dose on Day 35 or Early Termination (Pre-dose on Day 35 or Early Termination); Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 1 (Pre-dose on Day 1); Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 1 (1 Hour Post-dose on Day 1); Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 1 (4 Hours Post-dose on Day 1); Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 10 (Pre-dose on Day 10); Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 28 (Pre-dose on Day 28); Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 28 (1 Hour Post-dose on Day 28); Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 28 (4 Hours Post-dose on Day 28); Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 8 Hours Post-dose on Day 28 (8 Hours Post-dose on Day 28); Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 24 Hours Post-dose on Day 28 (24 Hours Post-dose on Day 28); Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 35 or Early Termination (Pre-dose on Day 35 or Early Termination); Parathyroid Hormone (PTH) Level at Pre-dose on Day 1 (Pre-dose on Day 1); Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 1 (1 Hour Post-dose on Day 1); Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 1 (4 Hours Post-dose on Day 1); Parathyroid Hormone (PTH) Level at Pre-dose on Day 10 (Pre-dose on Day 10); Parathyroid Hormone (PTH) Level at Pre-dose on Day 28 (Pre-dose on Day 28); Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 28 (1 Hour Post-dose on Day 28); Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 28 (4 Hours Post-dose on Day 28); Parathyroid Hormone (PTH) Level at 8 Hours Post-dose on Day 28 (8 Hours Post-dose on Day 28); Parathyroid Hormone (PTH) Level at 24 Hours Post-dose on Day 28 (24 Hours Post-dose on Day 28); Parathyroid Hormone (PTH) Level at Pre-dose on Day 35 or Early Termination (Pre-dose on Day 35 or Early Termination); Osteoprotegerin (OPG) Level at Pre-dose on Day 1 (Pre-dose on Day 1); Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 1 (1 Hour Post-dose on Day 1); Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 1 (4 Hours Post-dose on Day 1); Osteoprotegerin (OPG) Level at Pre-dose on Day 10 (Pre-dose on Day 10); Osteoprotegerin (OPG) Level at Pre-dose on Day 28 (Pre-dose on Day 28); Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 28 (1 Hour Post-dose on Day 28); Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 28 (4 Hours Post-dose on Day 28); Osteoprotegerin (OPG) Level at 8 Hours Post-dose on Day 28 (8 Hours Post-dose on Day 28); Osteoprotegerin (OPG) Level at 24 Hours Post-dose on Day 28 (24 Hours Post-dose on Day 28); Osteoprotegerin(OPG) Level at Pre-dose on Day 35 or Early Termination (Pre-dose on Day 35 or Early Termination); Plasma Level of Matrix Metallopeptidase (MMP13) (Pre-dose on Day 1, 10, 28 and 35 or Early Termination; 1, 4 hours Post-dose on Day 1, 28; 8, 24 hours Post-dose on Day 28); Plasma Level of Interleukin-34 (IL-34) and Interleukin-18 (IL-18) (Pre-dose on Day 1, 10, 28 and 35 or Early Termination; 1, 4 hours Post-dose on Day 1, 28; 8, 24 hours Post-dose on Day 28); Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 1 (Pre-dose on Day 1); Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 1 (1 Hour Post-dose on Day 1); Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 4 Hours Post-dose on Day 1 (4 Hours Post-dose on Day 1); Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 10 (Pre-dose on Day 10); Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 28 (Pre-dose on Day 28); Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 28 (1 Hour Post-dose on Day 28); Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 4 Hours Post-dose on Day 28 (4 Hours Post-dose on Day 28); Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 8 Hours Post-dose on Day 28 (8 Hours Post-dose on Day 28); Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 24 Hours Post-dose on Day 28 (24 Hours Post-dose on Day 28); Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 35 or Early Termination (Pre-dose on Day 35 or Early Termination); Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 1 (Pre-dose on Day 1); Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 1 (1 Hour Post-dose on Day 1); Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 1 (4 Hours Post-dose on Day 1); Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 10 (Pre-dose on Day 10); Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 28 (Pre-dose on Day 28); Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 28 (1 Hour Post-dose on Day 28); Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 28 (4 Hours Post-dose on Day 28); Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 8 Hours Post-dose on Day 28 (8 Hours Post-dose on Day 28); Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 24 Hours Post-dose on Day 28 (24 Hours Post-dose on Day 28); Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 35 or Early Termination (Pre-dose on Day 35 or Early Termination); Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 1 (Pre-dose on Day 1); Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 10 (Pre-dose on Day 10); Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 28 (Pre-dose on Day 28); Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at 24 Hours Post-dose on Day 28 (24 Hours Post-dose on Day 28); Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 35 or Early Termination (Pre-dose on Day 35 or Early Termination)
D: Percentage of Participants With American College of Rheumatology-ACR20 Response (Baseline, Week 24); Change From Baseline in Modified Total Sharp-Genant Score at Week 52 (Baseline, Week 52); Change in Physical Function as Measured by the Area Under the Curve (AUC) for the Change From Baseline in the Health Assessment Questionnaire (HAQ) Disability Index at Week 52 (Baseline to Week 52); Change From Baseline in the Modified Total Sharp-Genant Score at Week 104 (Baseline, Week 104); Change in Physical Function as Measured by the Area Under the Curve for the Change From Baseline in the Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 104 (Baseline to Week 104)

Answer: D