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A Study of Tocilizumab Plus Non-biological DMARD in Patients With Moderate to Severe Rheumatoid Arthritis and an Inadequate Response to Non-biological DMARDs

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ClinicalTrials.gov Identifier: NCT01034397
Recruitment Status : Completed
First Posted : December 17, 2009
Results First Posted : February 6, 2015
Last Update Posted : March 29, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: tocilizumab [RoActemra/Actemra]
Drug: placebo
Drug: non-biological DMARDs
Enrollment 54
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Tocilizumab 8 Milligrams Per Kilogram (mg/kg) Placebo
Hide Arm/Group Description Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) intravenously (IV) once every 4 weeks for 24 weeks. Participants received placebo IV once every 4 weeks for a maximum of 24 weeks. At 12 weeks, participants who did not respond to treatment (those who did not show improvement of greater than or equal to [≥]20 percent [%] in tender joint count and swollen joint count) were offered rescue therapy with open-label tocilizumab 8 mg/kg every 4 weeks through Week 24.
Period Title: Overall Study
Started 35 19
Completed 28 17
Not Completed 7 2
Reason Not Completed
Lack of compliance             0             1
Lack of Efficacy             3             0
Adverse Event             4             0
Not specified             0             1
Arm/Group Title Placebo Tocilizumab 8 mg/kg Total
Hide Arm/Group Description Participants received placebo IV once every 4 weeks for a maximum of 24 weeks. At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in tender joint count and swollen joint count) were offered rescue therapy with open-label tocilizumab 8 mg/kg every 4 weeks through Week 24. Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 24 weeks. Total of all reporting groups
Overall Number of Baseline Participants 19 35 54
Hide Baseline Analysis Population Description
Intent-to Treat (ITT) population: all participants randomized who had at least one efficacy measurement performed.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 19 participants 35 participants 54 participants
54
(45 to 69)
54
(28 to 79)
54
(28 to 79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 35 participants 54 participants
Female
17
  89.5%
29
  82.9%
46
  85.2%
Male
2
  10.5%
6
  17.1%
8
  14.8%
1.Primary Outcome
Title Percent Change From Baseline to Week 12 in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score
Hide Description Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Three wrist regions (distal radioulnar joint, radiocarpal joint, the intercarpal and intermetacarpal joint) and the 2nd to 5th metacarpophalangeal (MCP) were assessed for synovitis via magnetic resonance imaging (MRI) and scored using a scale ranging from 0-3 where 0 is normal and scores 1-3 (mild, moderate, severe) are by thirds of the presumed volume of enhancing tissue in the synovial compartment. These values were then summed yielding scores of 0-9 in the wrist region, 0-12 for MCP joints, and 0-22 on the aggregate. A negative value in synovitis change from Baseline score indicates an improvement.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n (number) equals (=) number of participants assessed for the specified parameter
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in tender joint count [TJC] and swollen joint count [SJC]) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 30 17
Median (Full Range)
Unit of Measure: percent change
Wrist region (n=30,17)
-20.0
(-100.0 to 200.0)
-37.5
(-100.0 to 40.0)
2nd to 5th MCP joints (n=25,14)
-25.0
(-91.7 to 100.0)
0.0
(-100.0 to 100.0)
Total synovitis score (n=30,17)
-23.6
(-80.0 to 1200.0)
-25.0
(-69.2 to 60.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments Wrist region: Tocilizumab versus placebo; Since one-sided t-test was used all effects in the opposite direction of what was predicted have a p-value=1.
Method t-test, 1 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.026
Comments 2nd and 5th MCP joints: Tocilizumab versus placebo
Method t-test, 1 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments Total synovitis score: Tocilizumab versus placebo; Since one-sided t-test was used all effects in the opposite direction of what was predicted have a p-value=1.
Method t-test, 1 sided
Comments [Not Specified]
2.Secondary Outcome
Title Percent Change From Baseline to Week 12 in OMERACT RAMRIS Score
Hide Description RAMRIS score is the sum of its core components: Synovitis Score, Edema Score, and Erosion Score. Synovitis scored from 0 (normal) to 9 (maximum distension of synovial cavity). Edema scored 0 (normal) to 69 (maximum articular bone involvement). Erosion scored from 0 (normal) to 230 (maximum erosion of articular bone). RAMRIS=Synovial Score plus (+) Edema Score + Erosion Score. Minimum RAMRIS score=0 (normal), maximum RAMRIS score=308 (severe structural damage). For Synovial Score, Edema Score, Erosion Score, and RAMRIS score, increasing number=increasing severity.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 30 17
Median (Full Range)
Unit of Measure: percent change
-10.6
(-80.9 to 127.8)
-15.4
(-59.7 to 41.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.421
Comments Percentage Change in OMERACT RAMRIS global score; Tocilizumab versus placebo.
Method t-test, 1 sided
Comments [Not Specified]
3.Secondary Outcome
Title Absolute Change From Baseline to Week 12 in OMERACT RAMRIS Score
Hide Description RAMRIS score is the sum of its core components: Synovitis Score, Edema Score, and Erosion Score. Synovitis scored from 0 (normal) to 9 (maximum distension of synovial cavity). Edema scored 0 (normal) to 69 (maximum articular bone involvement). Erosion scored from 0 (normal) to 230 (maximum erosion of articular bone). RAMRIS=Synovial Score plus (+) Edema Score + Erosion Score. Minimum RAMRIS score=0 (normal), maximum RAMRIS score=308 (severe structural damage). For Synovial Score, Edema Score, Erosion Score, and RAMRIS score, increasing number=increasing severity.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 30 17
Median (Full Range)
Unit of Measure: units on a scale
-5.5
(-38.0 to 23.0)
-7.0
(-43.0 to 15.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.434
Comments Absolute change in OMERACT RAMRIS global score; Placebo versus Tocilizumab
Method t-test, 1 sided
Comments [Not Specified]
4.Secondary Outcome
Title Percent Change From Baseline to Week 24 in OMERACT RAMRIS Score
Hide Description RAMRIS score is the sum of its core components: Synovitis Score, Edema Score, and Erosion Score. Synovitis scored from 0 (normal) to 9 (maximum distension of synovial cavity). Edema scored 0 (normal) to 69 (maximum articular bone involvement). Erosion scored from 0 (normal) to 230 (maximum erosion of articular bone). RAMRIS=Synovial Score + Edema Score + Erosion Score. Minimum RAMRIS score=0 (normal), maximum RAMRIS score=308 (severe structural damage). For Synovial Score, Edema Score, Erosion Score, and RAMRIS score, increasing number=increasing severity.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; participants from the placebo group who did not show an improvement of ≥20% in TJC and SJC were offered recovery therapy with tocilizumab 8 mg/kg and were placed in Placebo-Tocilizumab 8 mg/kg group.
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 24 7 9
Median (Full Range)
Unit of Measure: percent change
-24.2
(-70.0 to 83.3)
-17.3
(-33.3 to -4.2)
-36.8
(-73.7 to 11.8)
5.Secondary Outcome
Title Absolute Change From Baseline to Week 24 in OMERACT RAMRIS Score
Hide Description RAMRIS score is the sum of its core components: Synovitis Score, Edema Score, and Erosion Score. Synovitis scored from 0 (normal) to 9 (maximum distension of synovial cavity). Edema scored 0 (normal) to 69 (maximum articular bone involvement). Erosion scored from 0 (normal) to 230 (maximum erosion of articular bone). RAMRIS=Synovial Score + Edema Score + Erosion Score. Minimum RAMRIS score=0 (normal), maximum RAMRIS score=308 (severe structural damage). For Synovial Score, Edema Score, Erosion Score, and RAMRIS score, increasing number=increasing severity.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; participants from the placebo group who did not show an improvement of ≥20% in TJC and SJC were offered recovery therapy with tocilizumab 8 mg/kg and were placed in Placebo-Tocilizumab 8 mg/kg group.
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 24 7 9
Median (Full Range)
Unit of Measure: units on a scale
-13.0
(-34.0 to 15.0)
-3.0
(-24.0 to -1.0)
-14.0
(-46.0 to 4.0)
6.Secondary Outcome
Title Absolute Change From Baseline to Week 12 in OMERACT-RAMRIS Synovitis Score
Hide Description Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Three wrist regions (distal radioulnar joint, radiocarpal joint, the intercarpal and intermetacarpal joint) and the 2nd to 5th MCP were assessed for synovitis via MRI and scored using a scale ranging from 0-3 where 0 is normal and scores 1-3 (mild, moderate, severe) are by thirds of the presumed volume of enhancing tissue in the synovial compartment. These values were then summed yielding scores of 0-9 in the wrist region, 0-12 for MCP joints, and 0-22 on the aggregate. A negative value in synovitis change from Baseline score indicates an improvement.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 30 17
Median (Full Range)
Unit of Measure: units on a scale
Wrist region
-1.0
(-6.0 to 3.0)
-2.0
(-8.0 to 2.0)
2nd to 5th MCP joints
-1.0
(-11.0 to 10.0)
0.0
(-4.0 to 6.0)
Total synovitis score
-2.0
(-14.0 to 12.0)
-2.0
(-9.0 to 5.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments Change in Wrist region; Tocilizumab versus placebo. Since one-sided t-test was used all effects in the opposite direction of what was predicted have a p-value=1.
Method t-test, 1 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.065
Comments Change in 2nd to 5th MCP; Tocilizumab versus placebo.
Method t-test, 1 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments Change in Total synovitis; Tocilizumab versus placebo. Since one-sided t-test was used all effects in the opposite direction of what was predicted have a p-value=1.
Method t-test, 1 sided
Comments [Not Specified]
7.Secondary Outcome
Title Absolute Change From Baseline to Week 24 in OMERACT-RAMRIS Synovitis Score
Hide Description Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Three wrist regions (distal radioulnar joint, radiocarpal joint, the intercarpal and intermetacarpal joint) and the 2nd to 5th MCP were assessed for synovitis via MRI and scored using a scale ranging from 0-3 where 0 is normal and scores 1-3 (mild, moderate, severe) are by thirds of the presumed volume of enhancing tissue in the synovial compartment. These values were then summed yielding scores of 0-9 in the wrist region, 0-12 for MCP joints, and 0-22 on the aggregate. A negative value in synovitis change from Baseline score indicates an improvement.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 24 7 9
Median (Full Range)
Unit of Measure: units on a scale
Wrist region
-1.0
(-7.0 to 2.0)
-2.0
(-5.0 to -1.0)
-2.0
(-5.0 to -1.0)
2nd to 5th MCP joints
-1.0
(-9.0 to 7.0)
0.0
(-1.0 to 6.0)
-1.0
(-9.0 to 3.0)
Total synovitis score
-3.0
(-9.0 to 9.0)
-1.0
(-5.0 to 3.0)
-3.0
(-10.0 to 0.0)
8.Secondary Outcome
Title Percent Change From Baseline to Week 12 in OMERACT RAMRIS Bone Erosion Score
Hide Description Bones from the wrist regions (carpal bones, distal radius, distal ulna and metacarpal bases) and the MCP joints (metacarpal heads and phalangeal bases) were assessed for erosion via MRI and scored separately based on the proportion of eroded bone compared to the 'assessed bone volume' judged from all available images. Scoring ranges from 0 (no erosion) to 10 (91-100%). For long bones, the 'assessed bone volume' is from the articular surface to a depth of 1 centimeter (cm) (if the articular surface is absent its best estimated position is used), and in carpal bones it is the whole bone. Results were summed, resulting in scores from 0 to 80 for the wrist region, 0 to 150 for the MCP joints, and 0 to 230 on aggregate. A negative value in change from Baseline score indicates an improvement.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 30 17
Median (Full Range)
Unit of Measure: percent change
-3.7
(-72.7 to 180.0)
0.0
(-60.6 to 41.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments Absolute Change in Bone erosion; Tocilizumab versus placebo. Since one-sided t-test was used all effects in the opposite direction of what was predicted have a p-value=1.
Method t-test, 1 sided
Comments [Not Specified]
9.Secondary Outcome
Title Absolute Change From Baseline to Week 12 in OMERACT RAMRIS Bone Erosion Score
Hide Description Bones from the wrist regions (carpal bones, distal radius, distal ulna and metacarpal bases) and the MCP joints (metacarpal heads and phalangeal bases) were assessed for erosion via MRI and scored separately based on the proportion of eroded bone compared to the 'assessed bone volume' judged from all available images. Scoring ranges from 0 (no erosion) to 10 (91-100%). For long bones, the 'assessed bone volume' is from the articular surface to a depth of 1 centimeter (cm) (if the articular surface is absent its best estimated position is used), and in carpal bones it is the whole bone. Results were summed, resulting in scores from 0 to 80 for the wrist region, 0 to 150 for the MCP joints, and 0 to 230 on aggregate. A negative value in change from Baseline score indicates an improvement.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 30 17
Median (Full Range)
Unit of Measure: units on a scale
-0.5
(-16.0 to 10.0)
0.0
(-20.0 to 5.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments Percentage Change in Bone erosion; Tocilizumab versus placebo. Since one-sided t-test was used all effects in the opposite direction of what was predicted have a p-value=1.
Method t-test, 1 sided
Comments [Not Specified]
10.Secondary Outcome
Title Percent Change From Baseline to Week 24 in OMERACT RAMRIS Bone Erosion Score
Hide Description Bones from the wrist regions (carpal bones, distal radius, distal ulna and metacarpal bases) and the MCP joints (metacarpal heads and phalangeal bases) were assessed for erosion via MRI and scored separately based on the proportion of eroded bone compared to the 'assessed bone volume' judged from all available images. Scoring ranges from 0 (no erosion) to 10 (91-100%). For long bones, the 'assessed bone volume' is from the articular surface to a depth of 1 cm (if the articular surface is absent its best estimated position is used), and in carpal bones it is the whole bone. Results were summed, resulting in scores from 0 to 80 for the wrist region, 0 to 150 for the MCP joints, and 0 to 230 on aggregate. A negative value in change from Baseline score indicates an improvement.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 24 7 9
Median (Full Range)
Unit of Measure: percent change
-6.6
(-66.7 to 140.0)
-12.0
(-51.5 to 10.0)
-5.0
(-80.3 to 33.3)
11.Secondary Outcome
Title Absolute Change From Baseline to Week 24 in OMERACT RAMRIS Bone Erosion Score
Hide Description Bones from the wrist regions (carpal bones, distal radius, distal ulna and metacarpal bases) and the MCP joints (metacarpal heads and phalangeal bases) were assessed for erosion via MRI and scored separately based on the proportion of eroded bone compared to the 'assessed bone volume' judged from all available images. Scoring ranges from 0 (no erosion) to 10 (91-100%). For long bones, the 'assessed bone volume' is from the articular surface to a depth of 1 cm (if the articular surface is absent its best estimated position is used), and in carpal bones it is the whole bone. Results were summed, resulting in scores from 0 to 80 for the wrist region, 0 to 150 for the MCP joints, and 0 to 230 on aggregate. A negative value in change from Baseline score indicates an improvement.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; participants from the placebo group who did not show an improvement of ≥ 20% in TJC and SJC were offered recovery therapy with tocilizumab 8mg/kg and were placed in Placebo-Tocilizumab 8mg/kg group.
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 24 7 9
Median (Full Range)
Unit of Measure: units on a scale
-1.5
(-9.0 to 7.0)
-2.0
(-17.0 to 1.0)
-2.0
(-15.0 to 4.0)
12.Secondary Outcome
Title Percent Change From Baseline to Week 12 in OMERACT RAMRIS Bone Edema Score
Hide Description Bones from the wrist regions (carpal bones, distal radius, distal ulna and metacarpal bases) and the MCP joints (metacarpal heads and phalangeal bases) were assessed for edema via MRI and scored separately based on the proportion of bone with edema. Scoring ranged from 0 to 3 as follows: 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. Summing these values yielded a scale from 0-45 for the wrist region, 0-24 for the MCP joints, and 0-69 on aggregate.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of participants assessed for the specified parameter at a given visit. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 30 17
Median (Full Range)
Unit of Measure: percent change
-17.1
(-100.0 to 66.7)
-15.0
(-83.3 to 137.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.266
Comments Percentage Change in Bone oedema; Tocilizumab versus placebo.
Method t-test, 1 sided
Comments [Not Specified]
13.Secondary Outcome
Title Absolute Change From Baseline to Week 12 in OMERACT RAMRIS Bone Edema Score
Hide Description Bones from the wrist regions (carpal bones, distal radius, distal ulna and metacarpal bases) and the MCP joints (metacarpal heads and phalangeal bases) were assessed for edema via MRI and scored separately based on the proportion of bone with edema. Scoring ranged from 0 to 3 as follows: 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. Summing these values yielded a scale from 0-45 for the wrist region, 0-24 for the MCP joints, and 0-69 on aggregate.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of participants assessed for the specified parameter at a given visit. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 30 17
Median (Full Range)
Unit of Measure: units on a scale
-3.0
(-19.0 to 7.0)
-2.0
(-25.0 to 11.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.337
Comments Absolute Change in Bone edema; Tocilizumab versus placebo.
Method t-test, 1 sided
Comments [Not Specified]
14.Secondary Outcome
Title Percent Change From Baseline to Week 24 in OMERACT RAMRIS Bone Edema Score
Hide Description Bones from the wrist regions (carpal bones, distal radius, distal ulna and metacarpal bases) and the MCP joints (metacarpal heads and phalangeal bases) were assessed for edema via MRI and scored separately based on the proportion of bone with edema. Scoring ranged from 0 to 3 as follows: 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. Summing these values yielded a scale from 0-45 for the wrist region, 0-24 for the MCP joints, and 0-69 on aggregate.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; participants from the placebo group who did not show an improvement of ≥ 20% in TJC and SJC were offered recovery therapy with tocilizumab 8mg/kg and were placed in Placebo-Tocilizumab 8mg/kg group.
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 22 7 9
Median (Full Range)
Unit of Measure: percent change
-37.5
(-100.0 to 6.7)
-37.5
(-100.0 to 10.7)
-51.9
(-85.2 to 116.7)
15.Secondary Outcome
Title Absolute Change From Baseline to Week 24 in OMERACT RAMRIS Bone Edema Score
Hide Description Bones from the wrist regions (carpal bones, distal radius, distal ulna and metacarpal bases) and the MCP joints (metacarpal heads and phalangeal bases) were assessed for edema via MRI and scored separately based on the proportion of bone with edema. Scoring ranged from 0 to 3 as follows: 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. Summing these values yielded a scale from 0-45 for the wrist region, 0-24 for the MCP joints, and 0-69 on aggregate.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; participants from the placebo group who did not show an improvement of ≥ 20% in TJC and SJC were offered recovery therapy with tocilizumab 8mg/kg and were placed in Placebo-Tocilizumab 8mg/kg group.
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 24 7 9
Median (Full Range)
Unit of Measure: percent change
-5.5
(-29.0 to 1.0)
-3.0
(-9.0 to 3.0)
-10.0
(-23.0 to 7.0)
16.Secondary Outcome
Title Percent Change From Baseline to Week 12 in Dynamic Contrast Enhanced (DCE)-MRI Early Enhancement Rate (EER) Global Score
Hide Description Contrast enhancement was quantified in terms of initial rate of enhancement (IRE) and number of voxels (Nvox), which are extracted by examining individual signal intensity vs time curves derived from defined regions of interest (ROIs). A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. Maximum enhancement (ME)=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of signal intensity (SI) until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from all the assessed ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 12 9
Median (Full Range)
Unit of Measure: percent change
-38.7
(-55.3 to -18.4)
-12.1
(-78.3 to 31.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.114
Comments Percentage change in DCE-MRI EER (global); Placebo versus Tocilizumab
Method t-test, 1 sided
Comments [Not Specified]
17.Secondary Outcome
Title Absolute Change From Baseline to Week 12 in Dynamic Contrast Enhanced (DCE)-MRI Early Enhancement Rate (EER) Global Score
Hide Description Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from all the assessed ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 12 9
Median (Full Range)
Unit of Measure: units on a scale
-0.002
(-0.004 to 0.001)
-0.001
(-0.01 to 0.002)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.239
Comments Absolute Change in DCE-MRI EER; Tocilizumab versus placebo.
Method t-test, 1 sided
Comments [Not Specified]
18.Secondary Outcome
Title Percent Change From Baseline to Week 24 in DCE-MRI EER Global Score
Hide Description Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from all the assessed ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 10 4 5
Median (Full Range)
Unit of Measure: percent change
-45.4
(-68.6 to -11.8)
23.0
(-37.5 to 76.5)
-32.7
(-57.6 to -3.5)
19.Secondary Outcome
Title Absolute Change From Baseline to Week 24 in DCE-MRI EER Global Score
Hide Description Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from all the assessed ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population;
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 10 4 5
Median (Full Range)
Unit of Measure: units on a scale
-0.003
(-0.01 to 0.00)
0.0002
(0.00 to 0.01)
-0.002
(-0.01 to 0.00)
20.Secondary Outcome
Title Percent Change From Baseline to Week 12 in DCE-MRI EER MCP Score
Hide Description Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from the MCP ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 15 10
Median (Full Range)
Unit of Measure: percent change
-29.8
(-83.9 to 471.7)
-10.9
(-88.0 to 91.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.271
Comments Percentage change in DCE-MRI EER (MCP); Placebo versus Tocilizumab
Method t-test, 1 sided
Comments [Not Specified]
21.Secondary Outcome
Title Absolute Change From Baseline to Week 12 in DCE-MRI EER MCP Score
Hide Description Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from the MCP ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 15 10
Median (Full Range)
Unit of Measure: units on a scale
-0.002
(-0.01 to 0.00)
-0.001
(-0.02 to 0.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.370
Comments Absolute change in DCE-MRI EER (MCP); Placebo versus Tocilizumab
Method t-test, 1 sided
Comments [Not Specified]
22.Secondary Outcome
Title Percent Change From Baseline to Week 24 in DCE-MRI EER MCP Score
Hide Description Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from the MCP ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population;
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 12 5 5
Median (Full Range)
Unit of Measure: percent change
-32.3
(-100.0 to 40.0)
15.0
(-56.9 to 45.7)
-29.1
(-66.8 to 7.5)
23.Secondary Outcome
Title Absolute Change From Baseline to Week 24 in DCE-MRI EER MCP Score
Hide Description Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from the MCP ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population;
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 12 5 5
Median (Full Range)
Unit of Measure: units on a scale
-0.002
(-0.01 to 0.00)
0.001
(0.00 to 0.01)
-0.001
(-0.01 to 0.00)
24.Secondary Outcome
Title Percent Change From Baseline to Week 12 in DCE-MRI EER Wrist Score
Hide Description Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from the wrist ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 15 10
Median (Full Range)
Unit of Measure: percent change
-24.8
(-81.6 to 102.1)
-19.1
(-84.3 to 111.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments Percentage and absolute change in DCE-MRI EER (wrist); Placebo versus Tocilizumab
Method t-test, 1 sided
Comments [Not Specified]
25.Secondary Outcome
Title Absolute Change From Baseline to Week 12 in DCE-MRI EER Wrist Score
Hide Description Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from the wrist ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 15 10
Median (Full Range)
Unit of Measure: units on a scale
-0.002
(-0.01 to 0.00)
-0.001
(-0.01 to 0.00)
26.Secondary Outcome
Title Percent Change From Baseline to Week 24 in DCE-MRI EER Wrist Score
Hide Description Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from the wrist ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 12 5 5
Median (Full Range)
Unit of Measure: percent change
-27.0
(-80.0 to 59.1)
1.4
(-4.9 to 102.4)
-54.8
(-67.5 to -30.5)
27.Secondary Outcome
Title Absolute Change From Baseline to Week 24 in DCE-MRI EER Wrist Score
Hide Description Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from the wrist ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 12 5 5
Median (Full Range)
Unit of Measure: units on a scale
-0.002
(-0.01 to 0.00)
0.0001
(0.00 to 0.02)
-0.004
(-0.01 to 0.00)
28.Secondary Outcome
Title Disease Activity Score Based on 28-Joint Count (DAS28)
Hide Description DAS28 was calculated from the number of swollen joints and tender joints (SJC and TJC) using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]) and global health assessment (participant rated global assessment of disease activity using 10-mm visual analog scale [VAS]); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of participants assessed for the specified parameter at a given visit. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 32 17 10
Median (Full Range)
Unit of Measure: units on a scale
Baseline (n=32,17,0)
5.7
(3.4 to 8.0)
6.2
(4.1 to 8.2)
NA [1] 
(NA to NA)
Week 12 (n=30,17,0)
2.6
(1.1 to 5.8)
5.6
(1.8 to 8.0)
NA [1] 
(NA to NA)
Week 24 (n=24,7,10)
2.1
(0.8 to 4.1)
3.9
(3.2 to 6.6)
3.2
(1.5 to 5.1)
[1]
Data for the Placebo group with recovery therapy were collected only at Weeks 16, 20, and 24.
29.Secondary Outcome
Title Change From Baseline to Week 12 in DAS28 Global Score
Hide Description DAS28 was calculated from the number of swollen joints and tender joints (SJC and TJC) using the 28-joint count, the ESR (mm/hr) and global health assessment (participant rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. Change in DAS28 global score was determined as the difference in the scores at baseline and Week 12. A negative number indicated improvement.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 30 15
Median (Full Range)
Unit of Measure: units on a scale
-2.99
(-5.23 to -0.40)
0.22
(-3.88 to 1.54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
30.Secondary Outcome
Title Change From Baseline to Week 24 in DAS28 Global Score
Hide Description DAS28 was calculated from the number of swollen joints and tender joints (SJC and TJC) using the 28-joint count, the ESR (mm/hr) and global health assessment (participant rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. Change in DAS28 global score was determined as the difference in the scores at baseline and Week 24. A negative number indicated improvement.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 24 6 9
Median (Full Range)
Unit of Measure: units on a scale
-3.4
(-6.5 to -1.8)
-1.2
(-5.0 to 0.6)
-2.9
(-4.1 to -1.5)
31.Secondary Outcome
Title Tender and Swollen Joint Counts
Hide Description TJC and SJC were determined using the 28 joint counts. Joints were classified as tender/not tender and swollen/not swollen and counted. The scores ranged from 0 to 28. Higher scores indicated higher disease activity.
Time Frame Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of participants assessed for the specified parameter at a given visit. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 32 19 10
Median (Full Range)
Unit of Measure: joints
TJC, Week 12 (n=30,17,0)
3.5
(0.0 to 28.0)
8.0
(2.0 to 28.0)
NA [1] 
(NA to NA)
TJC, Week 24 (n=26,7,10)
1.0
(0.0 to 7.0)
7.0
(3.0 to 12.0)
5.5
(0.0 to 12.0)
SJC, Week 12 (n=30,17,0)
1.5
(0.0 to 12.0)
8.0
(0.0 to 24.0)
NA [1] 
(NA to NA)
SJC, Week 24 (n=26,7,10)
0.0
(0.0 to 4.0)
5.0
(1.0 to 17.0)
2.5
(1.0 to 9.0)
[1]
Data for the Placebo group with recovery therapy were collected only at Weeks, 16, 20 and 24
32.Secondary Outcome
Title Change From Baseline to Week 12 in TJC
Hide Description Change in TJC was determined as the difference in the number of tender joints at baseline and the number at Week 12. A negative number indicated improvement.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 30 17
Median (Full Range)
Unit of Measure: tender joints
-6.5
(-17.0 to 0.0)
-2.0
(-16.0 to 10.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.067
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
33.Secondary Outcome
Title Change From Baseline to Week 24 in TJC
Hide Description Change in TJC was determined as the difference in the number of tender joints at baseline and the number at Week 24. A negative number indicated improvement.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 26 7 10
Median (Full Range)
Unit of Measure: tender joints
-8.5
(-26.0 to 0.0)
-5.0
(-21.0 to 0.0)
-7.5
(-22.0 to 0.0)
34.Secondary Outcome
Title Change From Baseline to Week 12 in SJC
Hide Description Change in SJC was determined as the difference in the number of swollen joints at baseline and the number at Week 12. A negative number indicated improvement.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 30 17
Median (Full Range)
Unit of Measure: swollen joints
-7.0
(-19.0 to -1.0)
-1.0
(-13.0 to 10.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
35.Secondary Outcome
Title Change From Baseline to Week 24 in SJC
Hide Description Change in SJC was determined as the difference in the number of swollen joints at baseline and the number at Week 24. A negative number indicated improvement.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 26 7 10
Median (Full Range)
Unit of Measure: swollen joints
-8.5
(-23.0 to -2.0)
-7.0
(-21.0 to 1.0)
-5.0
(-8.0 to 0.0)
36.Secondary Outcome
Title Change From Baseline to Week 12 in Patient Global Assessment of Disease Activity
Hide Description General health was assessed using the Patient Global Assessment of Disease Activity, a 0 to 10 mm VAS, where 0 mm = very well and 10 mm = extremely bad. Participants were asked to answer the following question: “In general how would you rate your health over the last 2-3 weeks?”. Participants responded by marking the line and the distance from the left edge was recorded.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 30 17
Median (Full Range)
Unit of Measure: mm
-3.8
(-9.4 to 2.0)
0.2
(-6.6 to 6.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
37.Secondary Outcome
Title Change From Baseline to Week 24 in Patient Global Assessment of Disease Activity
Hide Description General health was assessed using the Patient Global Assessment of Disease Activity, a 0 to 10 mm VAS, where 0 mm = very well and 10 mm = extremely bad. Participants were asked to answer the following question: “In general how would you rate your health over the last 2-3 weeks?”. Participants responded by marking the line and the distance from the left edge was recorded.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 26 7 10
Median (Full Range)
Unit of Measure: mm
-4.4
(-9.5 to 2.6)
-1.5
(-7.1 to 3.7)
-1.4
(-5.4 to 1.0)
38.Secondary Outcome
Title Patient Global Assessment of Pain
Hide Description Patient's Global Assessment of Pain was assessed using a 10-mm horizontal VAS (0 to 10 mm) where 0=pain absent and 10=intolerable pain. Participants responded by placing a mark on the line to indicate their current level of pain; the distance from the left edge to the mark was recorded.
Time Frame Baseline, Weeks 4, 8, 12, 16, 20, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of participants assessed for the specific parameter at a given visit. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 32 19 10
Median (Full Range)
Unit of Measure: mm
Baseline (n=32,19,0)
5.2
(2.6 to 10.0)
5.1
(1.1 to 10.0)
NA [1] 
(NA to NA)
Week 4 (n= 31,18,0)
3.2
(0.4 to 7.4)
5.1
(1.3 to 10.0)
NA [1] 
(NA to NA)
Week 8 (n=31,17,0)
2.8
(0.0 to 8.6)
4.9
(1.9 to 8.3)
NA [1] 
(NA to NA)
Week 12 (n=30,17,0)
2.2
(0.0 to 8.0)
4.8
(1.0 to 8.6)
NA [1] 
(NA to NA)
Week 16 (n=26,7,10)
2.4
(0.0 to 6.6)
3.8
(0.4 to 8.2)
5.2
(1.5 to 8.8)
Week 20 (n=26,7,10)
1.5
(0.0 to 6.7)
5.0
(2.0 to 6.5)
3.8
(0.9 to 7.2)
Week 24 (n=26,7,10)
1.2
(0.0 to 8.0)
5.3
(1.5 to 6.6)
3.1
(0.7 to 6.2)
[1]
Data for the Placebo group with recovery therapy were collected only at Weeks 16, 20, and 24.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Change from Baseline to Week 12
Method Friedman's T test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.500
Comments Change from Baseline to Week 12
Method Friedman's T test
Comments [Not Specified]
39.Secondary Outcome
Title Change From Baseline to Week 12 in Patient Global Assessment of Pain
Hide Description Patient's Global Assessment of Pain was assessed using a 10-mm horizontal VAS (0 to 10 mm) where 0=pain absent and 10=intolerable pain. Participants responded by placing a mark on the line to indicate their current level of pain; the distance from the left edge to the mark was recorded. Change in Patient Global Assessment of Pain was determined as the difference in the scores at baseline and Week 12. A negative number indicated improvement.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 30 17
Median (Full Range)
Unit of Measure: mm
-3.3
(-9.1 to 3.0)
-0.3
(-8.2 to 5.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
40.Secondary Outcome
Title Change From Baseline to Week 24 in Patient Global Assessment of Pain
Hide Description Patient's Global Assessment of Pain was assessed using a 10-mm horizontal VAS (0 to 10 mm) where 0=pain absent and 10=intolerable pain. Participants responded by placing a mark on the line to indicate their current level of pain; the distance from the left edge to the mark was recorded. Change in Patient Global Assessment of Pain was determined as the difference in the scores at baseline and Week 24. A negative number indicated improvement.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 26 7 10
Median (Full Range)
Unit of Measure: mm
-3.7
(-9.4 to 2.8)
-3.4
(-4.4 to 3.2)
-1.5
(-5.9 to 1.9)
41.Secondary Outcome
Title Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores
Hide Description The HAQ-DI includes 20 questions concerning participant’s activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant’s everyday activities: 0=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of participants assessed for the specified parameter at a given visit. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 32 19 10
Median (Full Range)
Unit of Measure: units on a scale
Global score, Baseline (n=30,16,0)
2.1
(1.3 to 2.9)
2.3
(1.4 to 2.9)
NA [1] 
(NA to NA)
Global score, Week 12 (n=28,13,0)
1.5
(1.0 to 2.5)
2.3
(1.4 to 3.0)
NA [1] 
(NA to NA)
Global score, Week 24 (n=26,7,10)
1.3
(1.0 to 2.8)
2.1
(1.6 to 2.5)
2.1
(1.4 to 2.7)
Dressing/grooming, Baseline (n=31,18,0)
2.0
(1.0 to 3.0)
2.0
(1.0 to 3.0)
NA [1] 
(NA to NA)
Dressing/grooming, Week 12 (n=30,16,0)
1.0
(0.0 to 3.0)
2.0
(1.0 to 3.0)
NA [1] 
(NA to NA)
Dressing/grooming, Week 24 (n=26,7,10)
1.0
(1.0 to 3.0)
2.0
(1.0 to 3.0)
2.0
(1.0 to 3.0)
Arising, Baseline (n=32,19,0)
2.0
(1.0 to 3.0)
2.0
(1.0 to 3.0)
NA [1] 
(NA to NA)
Arising, Week 12 (n=30,17,0)
1.0
(1.0 to 3.0)
2.0
(0.0 to 3.0)
NA [1] 
(NA to NA)
Arising, Week 24 (n=26,7,10)
1.0
(1.0 to 3.0)
2.0
(1.0 to 2.0)
2.0
(1.0 to 3.0)
Eating, Baseline (n=26,14,0)
2.0
(1.0 to 3.0)
3.0
(1.0 to 3.0)
NA [1] 
(NA to NA)
Eating, Week 12 (n=27,10,0)
2.0
(1.0 to 3.0)
3.0
(2.0 to 3.0)
NA [1] 
(NA to NA)
Eating, Week 24 (n=24,7,9)
1.0
(1.0 to 3.0)
3.0
(2.0 to 3.0)
2.0
(2.0 to 3.0)
Walking, Baseline (n=32,19,0)
2.0
(1.0 to 3.0)
2.0
(1.0 to 3.0)
NA [1] 
(NA to NA)
Walking, Week 12 (n=30,17,0)
1.0
(0.0 to 3.0)
2.0
(1.0 to 3.0)
NA [1] 
(NA to NA)
Walking, Week 24 (n=26,7,10)
1.0
(1.0 to 3.0)
2.0
(2.0 to 3.0)
2.0
(1.0 to 3.0)
Hygiene, Baseline (n=31,18,0)
2.0
(1.0 to 3.0)
2.0
(1.0 to 3.0)
NA [1] 
(NA to NA)
Hygiene, Week 12 (n=30,17,0)
1.0
(0.0 to 3.0)
2.0
(0.0 to 3.0)
NA [1] 
(NA to NA)
Hygiene, Week 24 (n=26,7,10)
1.0
(1.0 to 3.0)
2.0
(1.0 to 2.0)
2.0
(1.0 to 2.0)
Reach, Baseline (n=24,12,0)
2.0
(1.0 to 3.0)
3.0
(1.0 to 3.0)
NA [1] 
(NA to NA)
Reach, Week 12 (n=26,10,0)
2.0
(0.0 to 3.0)
2.0
(0.0 to 3.0)
NA [1] 
(NA to NA)
Reach, Week 24 (n=23,7,8)
2.0
(1.0 to 3.0)
2.0
(2.0 to 2.0)
2.5
(1.0 to 3.0)
Grip, Baseline (n=29,18,0)
2.0
(1.0 to 3.0)
2.0
(1.0 to 3.0)
NA [1] 
(NA to NA)
Grip, Week 12 (n=29,14,0)
1.0
(0.0 to 3.0)
2.0
(0.0 to 3.0)
NA [1] 
(NA to NA)
Grip, Week 24 (n=26,7,9)
1.0
(1.0 to 3.0)
2.0
(2.0 to 3.0)
2.0
(2.0 to 3.0)
Activity, Baseline (n=31,15,0)
2.0
(1.0 to 3.0)
2.0
(2.0 to 3.0)
NA [1] 
(NA to NA)
Activity, Week 12 (n=29,14,0)
2.0
(0.0 to 3.0)
2.0
(0.0 to 3.0)
NA [1] 
(NA to NA)
Activity, Week 24 (n=25,7,8)
1.0
(1.0 to 3.0)
2.0
(2.0 to 2.0)
2.0
(2.0 to 3.0)
[1]
Data for the Placebo group with recovery therapy were collected only at Week 24.
42.Secondary Outcome
Title Change From Baseline to Week 12 in Erythrocyte Sedimentation Rate (ESR)
Hide Description ESR is an inflammatory marker and is used to assess disease activity in rheumatoid arthritis (RA). A reduction in ESR indicates improvement.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 30 15
Median (Full Range)
Unit of Measure: mm/hr
-19.0
(-93.0 to 0.0)
2.0
(-49.0 to 39.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
43.Secondary Outcome
Title Change From Baseline to Week 24 in ESR
Hide Description ESR is an inflammatory marker and is used to assess disease activity in RA. A reduction in ESR indicates improvement.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 24 6 9
Median (Full Range)
Unit of Measure: mm/hr
-20.0
(-95.0 to 5.0)
-9.0
(-47.0 to 3.0)
-27.0
(-75.0 to -7.0)
44.Secondary Outcome
Title Change From Baseline to Week 12 in C-Reactive Protein (CRP)
Hide Description The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. CRP was measured in milligrams per deciliter (mg/dL).
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 29 15
Median (Full Range)
Unit of Measure: mg/dL
-0.9
(-8.0 to 0.0)
-0.1
(-3.9 to 2.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
45.Secondary Outcome
Title Change From Baseline to Week 24 in CRP
Hide Description The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 24 5 5
Median (Full Range)
Unit of Measure: mg/dL
-1.2
(-8.0 to 0.0)
-0.2
(-2.9 to -0.02)
-0.6
(-9.7 to 0.0)
46.Secondary Outcome
Title Change From Baseline to Week 12 in Serum Cortisol
Hide Description Change in serum cortisol was determined as the difference in the scores at Baseline and Week 12.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 29 16
Median (Full Range)
Unit of Measure: mg/dL
-1.4
(-53.0 to 102.3)
2.5
(-31.6 to 119.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.118
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
47.Secondary Outcome
Title Change From Baseline to Week 24 in Serum Cortisol
Hide Description Change in serum cortisol was determined as the difference in the scores at Baseline and Week 24.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population;
Arm/Group Title Tocilizumab Placebo Placebo-Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 24 weeks
Participants received placebo IV once every 4 weeks for a maximum of 24 weeks. At 12 weeks, participants who did not respond to treatment (those who did not show improvement of at least 20% in tender joint count and swollen joint count) were offered rescue therapy with open-label tocilizumab 8 mg/kg every 4 weeks.
At 12 Weeks participants who did not show an improvement of ≥20% in tender and swollen joint counts were offered a rescue therapy with open-label tocilizumab 8mg/kg every 4 weeks
Overall Number of Participants Analyzed 25 7 10
Median (Full Range)
Unit of Measure: mg/dL
-2.5
(-40.1 to 51.8)
-5.2
(-32.0 to 6.0)
-5.1
(-63.2 to 106.2)
48.Secondary Outcome
Title Change From Baseline to Week 12 in Plasma Adrenocorticotrophic Hormone (ACTH)
Hide Description Change in Plasma ACTH was determined as the difference in the scores at Baseline and Week 12.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 28 15
Median (Full Range)
Unit of Measure: mg/dL
0.00
(-10.27 to 7.41)
0.00
(-7.62 to 4.67)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
49.Secondary Outcome
Title Change From Baseline to Week 24 in Plasma ACTH
Hide Description Change in plasma ACTH was determined as the difference in the scores at baseline and Week 24.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Patient's Global Assessment of Pain was assessed using a 10-mm horizontal VAS (0 to 10 mm) where 0=pain absent and 10=intolerable pain. Participants responded by placing a mark on the line to indicate their current level of pain; the distance from the left edge to the mark was recorded. Change in Patient Global Assessment of Pain was determined as the difference in the scores at baseline and Week 12. A negative number indicated improvement.
Overall Number of Participants Analyzed 24 6 10
Median (Full Range)
Unit of Measure: mg/dL
-0.4
(-13.7 to 12.7)
-0.3
(-2.0 to 0.0)
0.8
(-1.9 to 4.1)
50.Secondary Outcome
Title Change From Baseline to Week 12 in Serum Androstenedione
Hide Description Change in serum androstenedione was determined as the difference in the scores at Baseline and Week 12.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 28 16
Median (Full Range)
Unit of Measure: mg/dL
0.01
(-0.57 to 0.29)
0.01
(-0.12 to 0.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.437
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
51.Secondary Outcome
Title Change From Baseline to Week 12 in 17 Hydroxy Progesterone (17OHP)
Hide Description Change in 17OHP was determined as the difference in the scores at Baseline and Week 12.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 28 15
Median (Full Range)
Unit of Measure: mg/dL
-0.01
(-1.90 to 1.86)
-0.03
(-0.60 to 0.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
52.Secondary Outcome
Title Change From Baseline to Week 24 in Serum Androstenedione
Hide Description Change in serum androstenedione was determined as the difference in the scores at Baseline and Week 24.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 25 6 10
Median (Full Range)
Unit of Measure: mg/dL
0.02
(-1.56 to 0.70)
0.01
(-0.10 to 0.06)
-0.002
(-0.71 to 0.36)
53.Secondary Outcome
Title Change From Baseline to Week 24 in 17OHP
Hide Description Change in 17OHP was determined as the difference in the scores at Baseline and Week 24.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 23 6 10
Median (Full Range)
Unit of Measure: mg/dL
-0.01
(-1.97 to 1.03)
-0.07
(-0.86 to 0.46)
-0.02
(-0.50 to 0.20)
54.Secondary Outcome
Title Change From Baseline to Week 12 in Serum Dehydroepiandrosterone (DHEA)
Hide Description Change in DHEA was determined as the difference in the scores at Baseline and Week 12.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 28 15
Median (Full Range)
Unit of Measure: mg/dL
-0.07
(-6.09 to 2.90)
0.00
(-5.87 to 4.03)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.190
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
55.Secondary Outcome
Title Change From Baseline to Week 24 in Serum DHEA
Hide Description Change in DHEA was determined as the difference in the scores at Baseline and Week 24.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 24 6 10
Median (Full Range)
Unit of Measure: mg/dL
0.17
(-5.67 to 4.07)
-0.73
(-3.45 to 2.50)
0.40
(-10.43 to 3.38)
56.Secondary Outcome
Title Change From Baseline to Week 12 in Neuropeptide Y
Hide Description Change in Neuropeptide Y was determined as the difference in the scores at Baseline and Week 12.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 29 16
Median (Full Range)
Unit of Measure: mg/dL
-13.3
(-91.4 to 60.3)
-0.7
(-45.4 to 51.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab 8 mg/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.051
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
57.Secondary Outcome
Title Change From Baseline to Week 24 in Neuropeptide Y
Hide Description Change in Neuropeptide Y was determined as the difference in the scores at Baseline and Week 24.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions).
Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
Overall Number of Participants Analyzed 24 6 9
Median (Full Range)
Unit of Measure: mg/dL
-11.1
(-80.8 to 80.6)
-2.5
(-44.5 to 58.4)
-13.9
(-52.8 to 28.2)
Time Frame Adverse events were recorded from the day of screening until the end of study at Week 24.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Hide Arm/Group Description Participants received tocilizumab 8 mg/kg (minimum dose of 480 mg, maximum dose of 800 mg) IV once every 4 weeks for 20 weeks (total of 6 infusions). Participants received placebo IV once every 4 weeks for a maximum of 20 weeks (total of 6 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) were offered rescue therapy with open-label tocilizumab 8 mg/kg IV once every 4 weeks through Week 20. Participants received placebo IV once every 4 weeks for 12 weeks (total of 3 infusions). At 12 weeks, participants who did not respond to treatment (those who did not show improvement of ≥20% in TJC and SJC) received tocilizumab 8 mg/kg IV once every 4 weeks through Week 20.
All-Cause Mortality
Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/35 (5.71%)   0/10 (0.00%)   0/9 (0.00%) 
Infections and infestations       
Cellulitis * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Gluteal cleft cyst * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Tocilizumab 8 mg/kg Placebo Placebo-Tocilizumab 8 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   29/35 (82.86%)   7/10 (70.00%)   6/9 (66.67%) 
Blood and lymphatic system disorders       
Hematoma cyclid of the right eye * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Neutropenia * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Anemia * 1  0/35 (0.00%)  1/10 (10.00%)  0/9 (0.00%) 
Urine Leukocyte elevation * 1  0/35 (0.00%)  1/10 (10.00%)  0/9 (0.00%) 
Varicose vein rupture * 1  0/35 (0.00%)  1/10 (10.00%)  0/9 (0.00%) 
Gastrointestinal disorders       
Blood Diarrhea * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Epigastric pain * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Vomiting * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Diarrhea * 1  0/35 (0.00%)  0/10 (0.00%)  1/9 (11.11%) 
Dyspepsia * 1  0/35 (0.00%)  0/10 (0.00%)  1/9 (11.11%) 
Gastroenteritis * 1  0/35 (0.00%)  0/10 (0.00%)  1/9 (11.11%) 
General disorders       
Back pain * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Cough * 1  1/35 (2.86%)  0/10 (0.00%)  1/9 (11.11%) 
Fall * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Finger cut * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Hoarseness * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Inter-digital wound * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Left leg cellulitis * 1  1/35 (2.86%)  1/10 (10.00%)  0/9 (0.00%) 
Nausea * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Tooth ache * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Flu-like syndrome * 1  0/35 (0.00%)  1/10 (10.00%)  1/9 (11.11%) 
Odynophagia * 1  0/35 (0.00%)  1/10 (10.00%)  0/9 (0.00%) 
Gingivorrhagea in patient with low platelets * 1  0/35 (0.00%)  0/10 (0.00%)  1/9 (11.11%) 
Sputum * 1  0/35 (0.00%)  0/10 (0.00%)  1/9 (11.11%) 
Hepatobiliary disorders       
Hepatotoxicity * 1  2/35 (5.71%)  2/10 (20.00%)  0/9 (0.00%) 
Hepatic toxicity * 1  2/35 (5.71%)  2/10 (20.00%)  0/9 (0.00%) 
Infections and infestations       
Urinary Tract infection * 1  4/35 (11.43%)  1/10 (10.00%)  0/9 (0.00%) 
Oral candidiasis * 1  0/35 (0.00%)  1/10 (10.00%)  0/9 (0.00%) 
Flu * 1  2/35 (5.71%)  0/10 (0.00%)  0/9 (0.00%) 
Herpes simplex in the lips * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Impetigo * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Infected traumatic right leg ulcer * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Pharyngitis * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Upper airways infection * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Vaginal labial folliculitis * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Mouth mucositis * 1  0/35 (0.00%)  0/10 (0.00%)  1/9 (11.11%) 
Investigations       
Hypercholesterolemia * 1  3/35 (8.57%)  1/10 (10.00%)  1/9 (11.11%) 
Abnormal liver function tests * 1  0/35 (0.00%)  1/10 (10.00%)  0/9 (0.00%) 
Liver Enzyme Elevation * 1  2/35 (5.71%)  0/10 (0.00%)  0/9 (0.00%) 
Elevated ALT * 1  2/35 (5.71%)  0/10 (0.00%)  0/9 (0.00%) 
Transaminase Elevation * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Bilirubin Elevation * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Dislipidemia * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Hypertriglyceridemia * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Nitritis Elevation * 1  0/35 (0.00%)  1/10 (10.00%)  0/9 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Leg ulcer * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Oral aftosis * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Nervous system disorders       
Facial paralysis on the right side * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Renal and urinary disorders       
Mild renal failure * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Skin and subcutaneous tissue disorders       
Malar rash * 1  0/35 (0.00%)  1/10 (10.00%)  0/9 (0.00%) 
Eczema * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
Rash * 1  1/35 (2.86%)  0/10 (0.00%)  0/9 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but after the first publication or presentation that involves the overall study. Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann- LaRoche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01034397     History of Changes
Other Study ID Numbers: ML22648
2009-012218-30
First Submitted: December 16, 2009
First Posted: December 17, 2009
Results First Submitted: July 9, 2014
Results First Posted: February 6, 2015
Last Update Posted: March 29, 2018