Trial Outcomes & Findings for A Study of Tocilizumab Plus Non-biological DMARD in Patients With Moderate to Severe Rheumatoid Arthritis and an Inadequate Response to Non-biological DMARDs (NCT NCT01034397)

NCT ID: NCT01034397

Last Updated: 2018-03-29

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 54 participants
• Primary outcome timeframe: Week 12
• Results posted on: 2018-03-29

Participant Flow

Participant milestones

Measure	Tocilizumab 8 Milligrams Per Kilogram (mg/kg) 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.	Placebo 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.
Overall Study STARTED	35	19
Overall Study COMPLETED	28	17
Overall Study NOT COMPLETED	7	2

Reasons for withdrawal

Measure	Tocilizumab 8 Milligrams Per Kilogram (mg/kg) 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.	Placebo 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.
Overall Study Lack of compliance	0	1
Overall Study Lack of Efficacy	3	0
Overall Study Adverse Event	4	0
Overall Study Other	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo n=19 Participants 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.	Tocilizumab 8 mg/kg n=35 Participants 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 n=54 Participants Total of all reporting groups
Age, Continuous	54 years n=5 Participants	54 years n=7 Participants	54 years n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	29 Participants n=7 Participants	46 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 12

Population: ITT population; n (number) equals (=) number of participants assessed for the specified parameter

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.

Outcome measures

Measure	Placebo n=17 Participants 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.	Tocilizumab 8 mg/kg n=30 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
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 2nd to 5th MCP joints (n=25,14)	0.0 percent change Interval -100.0 to 100.0	-25.0 percent change Interval -91.7 to 100.0	—
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 Wrist region (n=30,17)	-37.5 percent change Interval -100.0 to 40.0	-20.0 percent change Interval -100.0 to 200.0	—
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 Total synovitis score (n=30,17)	-25.0 percent change Interval -69.2 to 60.0	-23.6 percent change Interval -80.0 to 1200.0	—

SECONDARY outcome

Timeframe: Week 12

Population: ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.

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.

Outcome measures

Measure	Placebo n=17 Participants 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.	Tocilizumab 8 mg/kg n=30 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Percent Change From Baseline to Week 12 in OMERACT RAMRIS Score	-15.4 percent change Interval -59.7 to 41.7	-10.6 percent change Interval -80.9 to 127.8	—

SECONDARY outcome

Timeframe: Week 12

Population: ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.

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.

Outcome measures

Measure	Placebo n=17 Participants 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.	Tocilizumab 8 mg/kg n=30 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Absolute Change From Baseline to Week 12 in OMERACT RAMRIS Score	-7.0 units on a scale Interval -43.0 to 15.0	-5.5 units on a scale Interval -38.0 to 23.0	—

SECONDARY outcome

Timeframe: Week 24

Population: 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.

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.

Outcome measures

Measure	Placebo n=7 Participants 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.	Tocilizumab 8 mg/kg n=24 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=9 Participants 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.
Percent Change From Baseline to Week 24 in OMERACT RAMRIS Score	-17.3 percent change Interval -33.3 to -4.2	-24.2 percent change Interval -70.0 to 83.3	-36.8 percent change Interval -73.7 to 11.8

SECONDARY outcome

Timeframe: Week 24

Population: 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.

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.

Outcome measures

Measure	Placebo n=7 Participants 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.	Tocilizumab 8 mg/kg n=24 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=9 Participants 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.
Absolute Change From Baseline to Week 24 in OMERACT RAMRIS Score	-3.0 units on a scale Interval -24.0 to -1.0	-13.0 units on a scale Interval -34.0 to 15.0	-14.0 units on a scale Interval -46.0 to 4.0

SECONDARY outcome

Timeframe: Week 12

Population: ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.

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.

Outcome measures

Measure	Placebo n=17 Participants 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.	Tocilizumab 8 mg/kg n=30 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Absolute Change From Baseline to Week 12 in OMERACT-RAMRIS Synovitis Score 2nd to 5th MCP joints	0.0 units on a scale Interval -4.0 to 6.0	-1.0 units on a scale Interval -11.0 to 10.0	—
Absolute Change From Baseline to Week 12 in OMERACT-RAMRIS Synovitis Score Total synovitis score	-2.0 units on a scale Interval -9.0 to 5.0	-2.0 units on a scale Interval -14.0 to 12.0	—
Absolute Change From Baseline to Week 12 in OMERACT-RAMRIS Synovitis Score Wrist region	-2.0 units on a scale Interval -8.0 to 2.0	-1.0 units on a scale Interval -6.0 to 3.0	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT population.

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.

Outcome measures

Measure	Placebo n=7 Participants 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.	Tocilizumab 8 mg/kg n=24 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=9 Participants 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.
Absolute Change From Baseline to Week 24 in OMERACT-RAMRIS Synovitis Score Total synovitis score	-1.0 units on a scale Interval -5.0 to 3.0	-3.0 units on a scale Interval -9.0 to 9.0	-3.0 units on a scale Interval -10.0 to 0.0
Absolute Change From Baseline to Week 24 in OMERACT-RAMRIS Synovitis Score Wrist region	-2.0 units on a scale Interval -5.0 to -1.0	-1.0 units on a scale Interval -7.0 to 2.0	-2.0 units on a scale Interval -5.0 to -1.0
Absolute Change From Baseline to Week 24 in OMERACT-RAMRIS Synovitis Score 2nd to 5th MCP joints	0.0 units on a scale Interval -1.0 to 6.0	-1.0 units on a scale Interval -9.0 to 7.0	-1.0 units on a scale Interval -9.0 to 3.0

SECONDARY outcome

Timeframe: Week 12

Population: ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.

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.

Outcome measures

Measure	Placebo n=17 Participants 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.	Tocilizumab 8 mg/kg n=30 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Percent Change From Baseline to Week 12 in OMERACT RAMRIS Bone Erosion Score	0.0 percent change Interval -60.6 to 41.7	-3.7 percent change Interval -72.7 to 180.0	—

SECONDARY outcome

Timeframe: Week 12

Population: ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.

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.

Outcome measures

Measure	Placebo n=17 Participants 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.	Tocilizumab 8 mg/kg n=30 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Absolute Change From Baseline to Week 12 in OMERACT RAMRIS Bone Erosion Score	0.0 units on a scale Interval -20.0 to 5.0	-0.5 units on a scale Interval -16.0 to 10.0	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT population

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.

Outcome measures

Measure	Placebo n=7 Participants 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.	Tocilizumab 8 mg/kg n=24 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=9 Participants 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.
Percent Change From Baseline to Week 24 in OMERACT RAMRIS Bone Erosion Score	-12.0 percent change Interval -51.5 to 10.0	-6.6 percent change Interval -66.7 to 140.0	-5.0 percent change Interval -80.3 to 33.3

SECONDARY outcome

Timeframe: Week 24

Population: 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.

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.

Outcome measures

Measure	Placebo n=7 Participants 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.	Tocilizumab 8 mg/kg n=24 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=9 Participants 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.
Absolute Change From Baseline to Week 24 in OMERACT RAMRIS Bone Erosion Score	-2.0 units on a scale Interval -17.0 to 1.0	-1.5 units on a scale Interval -9.0 to 7.0	-2.0 units on a scale Interval -15.0 to 4.0

SECONDARY outcome

Timeframe: Week 12

Population: 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.

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.

Outcome measures

Measure	Placebo n=17 Participants 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.	Tocilizumab 8 mg/kg n=30 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Percent Change From Baseline to Week 12 in OMERACT RAMRIS Bone Edema Score	-15.0 percent change Interval -83.3 to 137.5	-17.1 percent change Interval -100.0 to 66.7	—

SECONDARY outcome

Timeframe: Week 12

Population: 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.

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.

Outcome measures

Measure	Placebo n=17 Participants 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.	Tocilizumab 8 mg/kg n=30 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Absolute Change From Baseline to Week 12 in OMERACT RAMRIS Bone Edema Score	-2.0 units on a scale Interval -25.0 to 11.0	-3.0 units on a scale Interval -19.0 to 7.0	—

SECONDARY outcome

Timeframe: Week 24

Population: 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.

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.

Outcome measures

Measure	Placebo n=7 Participants 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.	Tocilizumab 8 mg/kg n=22 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=9 Participants 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.
Percent Change From Baseline to Week 24 in OMERACT RAMRIS Bone Edema Score	-37.5 percent change Interval -100.0 to 10.7	-37.5 percent change Interval -100.0 to 6.7	-51.9 percent change Interval -85.2 to 116.7

SECONDARY outcome

Timeframe: Week 24

Population: 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.

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.

Outcome measures

Measure	Placebo n=7 Participants 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.	Tocilizumab 8 mg/kg n=24 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=9 Participants 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.
Absolute Change From Baseline to Week 24 in OMERACT RAMRIS Bone Edema Score	-3.0 percent change Interval -9.0 to 3.0	-5.5 percent change Interval -29.0 to 1.0	-10.0 percent change Interval -23.0 to 7.0

SECONDARY outcome

Timeframe: Week 12

Population: ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.

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.

Outcome measures

Measure	Placebo n=9 Participants 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.	Tocilizumab 8 mg/kg n=12 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Percent Change From Baseline to Week 12 in Dynamic Contrast Enhanced (DCE)-MRI Early Enhancement Rate (EER) Global Score	-12.1 percent change Interval -78.3 to 31.0	-38.7 percent change Interval -55.3 to -18.4	—

SECONDARY outcome

Timeframe: Week 12

Population: ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.

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.

Outcome measures

Measure	Placebo n=9 Participants 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.	Tocilizumab 8 mg/kg n=12 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Absolute Change From Baseline to Week 12 in Dynamic Contrast Enhanced (DCE)-MRI Early Enhancement Rate (EER) Global Score	-0.001 units on a scale Interval -0.01 to 0.002	-0.002 units on a scale Interval -0.004 to 0.001	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT population

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.

Outcome measures

Measure	Placebo n=4 Participants 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.	Tocilizumab 8 mg/kg n=10 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=5 Participants 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.
Percent Change From Baseline to Week 24 in DCE-MRI EER Global Score	23.0 percent change Interval -37.5 to 76.5	-45.4 percent change Interval -68.6 to -11.8	-32.7 percent change Interval -57.6 to -3.5

SECONDARY outcome

Timeframe: Week 24

Population: ITT population;

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.

Outcome measures

Measure	Placebo n=4 Participants 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.	Tocilizumab 8 mg/kg n=10 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=5 Participants 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.
Absolute Change From Baseline to Week 24 in DCE-MRI EER Global Score	0.0002 units on a scale Interval 0.0 to 0.01	-0.003 units on a scale Interval -0.01 to 0.0	-0.002 units on a scale Interval -0.01 to 0.0

SECONDARY outcome

Timeframe: Week 12

Population: ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.

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.

Outcome measures

Measure	Placebo n=10 Participants 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.	Tocilizumab 8 mg/kg n=15 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Percent Change From Baseline to Week 12 in DCE-MRI EER MCP Score	-10.9 percent change Interval -88.0 to 91.1	-29.8 percent change Interval -83.9 to 471.7	—

SECONDARY outcome

Timeframe: Week 12

Population: ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.

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.

Outcome measures

Measure	Placebo n=10 Participants 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.	Tocilizumab 8 mg/kg n=15 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Absolute Change From Baseline to Week 12 in DCE-MRI EER MCP Score	-0.001 units on a scale Interval -0.02 to 0.0	-0.002 units on a scale Interval -0.01 to 0.0	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT population;

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.

Outcome measures

Measure	Placebo n=5 Participants 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.	Tocilizumab 8 mg/kg n=12 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=5 Participants 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.
Percent Change From Baseline to Week 24 in DCE-MRI EER MCP Score	15.0 percent change Interval -56.9 to 45.7	-32.3 percent change Interval -100.0 to 40.0	-29.1 percent change Interval -66.8 to 7.5

SECONDARY outcome

Timeframe: Week 24

Population: ITT population;

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.

Outcome measures

Measure	Placebo n=5 Participants 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.	Tocilizumab 8 mg/kg n=12 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=5 Participants 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.
Absolute Change From Baseline to Week 24 in DCE-MRI EER MCP Score	0.001 units on a scale Interval 0.0 to 0.01	-0.002 units on a scale Interval -0.01 to 0.0	-0.001 units on a scale Interval -0.01 to 0.0

SECONDARY outcome

Timeframe: Week 12

Population: ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.

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.

Outcome measures

Measure	Placebo n=10 Participants 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.	Tocilizumab 8 mg/kg n=15 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Percent Change From Baseline to Week 12 in DCE-MRI EER Wrist Score	-19.1 percent change Interval -84.3 to 111.4	-24.8 percent change Interval -81.6 to 102.1	—

SECONDARY outcome

Timeframe: Week 12

Population: ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.

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.

Outcome measures

Measure	Placebo n=10 Participants 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.	Tocilizumab 8 mg/kg n=15 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Absolute Change From Baseline to Week 12 in DCE-MRI EER Wrist Score	-0.001 units on a scale Interval -0.01 to 0.0	-0.002 units on a scale Interval -0.01 to 0.0	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT population

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.

Outcome measures

Measure	Placebo n=5 Participants 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.	Tocilizumab 8 mg/kg n=12 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=5 Participants 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.
Percent Change From Baseline to Week 24 in DCE-MRI EER Wrist Score	1.4 percent change Interval -4.9 to 102.4	-27.0 percent change Interval -80.0 to 59.1	-54.8 percent change Interval -67.5 to -30.5

SECONDARY outcome

Timeframe: Week 24

Population: ITT population

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.

Outcome measures

Measure	Placebo n=5 Participants 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.	Tocilizumab 8 mg/kg n=12 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=5 Participants 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.
Absolute Change From Baseline to Week 24 in DCE-MRI EER Wrist Score	0.0001 units on a scale Interval 0.0 to 0.02	-0.002 units on a scale Interval -0.01 to 0.0	-0.004 units on a scale Interval -0.01 to 0.0

SECONDARY outcome

Timeframe: Baseline, Weeks 12 and 24

Population: 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.

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.

Outcome measures

Measure	Placebo n=17 Participants 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.	Tocilizumab 8 mg/kg n=32 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=10 Participants 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.
Disease Activity Score Based on 28-Joint Count (DAS28) Baseline (n=32,17,0)	6.2 units on a scale Interval 4.1 to 8.2	5.7 units on a scale Interval 3.4 to 8.0	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Weeks 16, 20, and 24.
Disease Activity Score Based on 28-Joint Count (DAS28) Week 12 (n=30,17,0)	5.6 units on a scale Interval 1.8 to 8.0	2.6 units on a scale Interval 1.1 to 5.8	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Weeks 16, 20, and 24.
Disease Activity Score Based on 28-Joint Count (DAS28) Week 24 (n=24,7,10)	3.9 units on a scale Interval 3.2 to 6.6	2.1 units on a scale Interval 0.8 to 4.1	3.2 units on a scale Interval 1.5 to 5.1

SECONDARY outcome

Timeframe: Week 12

Population: ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.

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.

Outcome measures

Measure	Placebo n=15 Participants 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.	Tocilizumab 8 mg/kg n=30 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Change From Baseline to Week 12 in DAS28 Global Score	0.22 units on a scale Interval -3.88 to 1.54	-2.99 units on a scale Interval -5.23 to -0.4	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT population

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.

Outcome measures

Measure	Placebo n=6 Participants 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.	Tocilizumab 8 mg/kg n=24 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=9 Participants 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.
Change From Baseline to Week 24 in DAS28 Global Score	-1.2 units on a scale Interval -5.0 to 0.6	-3.4 units on a scale Interval -6.5 to -1.8	-2.9 units on a scale Interval -4.1 to -1.5

SECONDARY outcome

Timeframe: Weeks 12 and 24

Population: 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.

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.

Outcome measures

Measure	Placebo n=19 Participants 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.	Tocilizumab 8 mg/kg n=32 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=10 Participants 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.
Tender and Swollen Joint Counts TJC, Week 24 (n=26,7,10)	7.0 joints Interval 3.0 to 12.0	1.0 joints Interval 0.0 to 7.0	5.5 joints Interval 0.0 to 12.0
Tender and Swollen Joint Counts SJC, Week 12 (n=30,17,0)	8.0 joints Interval 0.0 to 24.0	1.5 joints Interval 0.0 to 12.0	NA joints Data for the Placebo group with recovery therapy were collected only at Weeks, 16, 20 and 24
Tender and Swollen Joint Counts SJC, Week 24 (n=26,7,10)	5.0 joints Interval 1.0 to 17.0	0.0 joints Interval 0.0 to 4.0	2.5 joints Interval 1.0 to 9.0
Tender and Swollen Joint Counts TJC, Week 12 (n=30,17,0)	8.0 joints Interval 2.0 to 28.0	3.5 joints Interval 0.0 to 28.0	NA joints Data for the Placebo group with recovery therapy were collected only at Weeks, 16, 20 and 24

SECONDARY outcome

Timeframe: Week 12

Population: ITT population

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.

Outcome measures

Measure	Placebo n=17 Participants 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.	Tocilizumab 8 mg/kg n=30 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Change From Baseline to Week 12 in TJC	-2.0 tender joints Interval -16.0 to 10.0	-6.5 tender joints Interval -17.0 to 0.0	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT population

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.

Outcome measures

Measure	Placebo n=7 Participants 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.	Tocilizumab 8 mg/kg n=26 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=10 Participants 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.
Change From Baseline to Week 24 in TJC	-5.0 tender joints Interval -21.0 to 0.0	-8.5 tender joints Interval -26.0 to 0.0	-7.5 tender joints Interval -22.0 to 0.0

SECONDARY outcome

Timeframe: Week 12

Population: ITT population

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.

Outcome measures

Measure	Placebo n=17 Participants 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.	Tocilizumab 8 mg/kg n=30 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Change From Baseline to Week 12 in SJC	-1.0 swollen joints Interval -13.0 to 10.0	-7.0 swollen joints Interval -19.0 to -1.0	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT population

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.

Outcome measures

Measure	Placebo n=7 Participants 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.	Tocilizumab 8 mg/kg n=26 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=10 Participants 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.
Change From Baseline to Week 24 in SJC	-7.0 swollen joints Interval -21.0 to 1.0	-8.5 swollen joints Interval -23.0 to -2.0	-5.0 swollen joints Interval -8.0 to 0.0

SECONDARY outcome

Timeframe: Week 12

Population: ITT population

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.

Outcome measures

Measure	Placebo n=17 Participants 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.	Tocilizumab 8 mg/kg n=30 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Change From Baseline to Week 12 in Patient Global Assessment of Disease Activity	0.2 mm Interval -6.6 to 6.8	-3.8 mm Interval -9.4 to 2.0	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT population

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.

Outcome measures

Measure	Placebo n=7 Participants 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.	Tocilizumab 8 mg/kg n=26 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=10 Participants 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.
Change From Baseline to Week 24 in Patient Global Assessment of Disease Activity	-1.5 mm Interval -7.1 to 3.7	-4.4 mm Interval -9.5 to 2.6	-1.4 mm Interval -5.4 to 1.0

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Placebo n=19 Participants 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.	Tocilizumab 8 mg/kg n=32 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=10 Participants 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.
Patient Global Assessment of Pain Baseline (n=32,19,0)	5.1 mm Interval 1.1 to 10.0	5.2 mm Interval 2.6 to 10.0	NA mm Data for the Placebo group with recovery therapy were collected only at Weeks 16, 20, and 24.
Patient Global Assessment of Pain Week 4 (n= 31,18,0)	5.1 mm Interval 1.3 to 10.0	3.2 mm Interval 0.4 to 7.4	NA mm Data for the Placebo group with recovery therapy were collected only at Weeks 16, 20, and 24.
Patient Global Assessment of Pain Week 12 (n=30,17,0)	4.8 mm Interval 1.0 to 8.6	2.2 mm Interval 0.0 to 8.0	NA mm Data for the Placebo group with recovery therapy were collected only at Weeks 16, 20, and 24.
Patient Global Assessment of Pain Week 20 (n=26,7,10)	5.0 mm Interval 2.0 to 6.5	1.5 mm Interval 0.0 to 6.7	3.8 mm Interval 0.9 to 7.2
Patient Global Assessment of Pain Week 24 (n=26,7,10)	5.3 mm Interval 1.5 to 6.6	1.2 mm Interval 0.0 to 8.0	3.1 mm Interval 0.7 to 6.2
Patient Global Assessment of Pain Week 8 (n=31,17,0)	4.9 mm Interval 1.9 to 8.3	2.8 mm Interval 0.0 to 8.6	NA mm Data for the Placebo group with recovery therapy were collected only at Weeks 16, 20, and 24.
Patient Global Assessment of Pain Week 16 (n=26,7,10)	3.8 mm Interval 0.4 to 8.2	2.4 mm Interval 0.0 to 6.6	5.2 mm Interval 1.5 to 8.8

SECONDARY outcome

Timeframe: Week 12

Population: ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.

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.

Outcome measures

Measure	Placebo n=17 Participants 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.	Tocilizumab 8 mg/kg n=30 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Change From Baseline to Week 12 in Patient Global Assessment of Pain	-0.3 mm Interval -8.2 to 5.3	-3.3 mm Interval -9.1 to 3.0	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT population

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.

Outcome measures

Measure	Placebo n=7 Participants 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.	Tocilizumab 8 mg/kg n=26 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=10 Participants 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.
Change From Baseline to Week 24 in Patient Global Assessment of Pain	-3.4 mm Interval -4.4 to 3.2	-3.7 mm Interval -9.4 to 2.8	-1.5 mm Interval -5.9 to 1.9

SECONDARY outcome

Timeframe: Baseline, Weeks 12 and 24

Population: 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.

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.

Outcome measures

Measure	Placebo n=19 Participants 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.	Tocilizumab 8 mg/kg n=32 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=10 Participants 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.
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Hygiene, Week 24 (n=26,7,10)	2.0 units on a scale Interval 1.0 to 2.0	1.0 units on a scale Interval 1.0 to 3.0	2.0 units on a scale Interval 1.0 to 2.0
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Hygiene, Week 12 (n=30,17,0)	2.0 units on a scale Interval 0.0 to 3.0	1.0 units on a scale Interval 0.0 to 3.0	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Week 24.
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Global score, Baseline (n=30,16,0)	2.3 units on a scale Interval 1.4 to 2.9	2.1 units on a scale Interval 1.3 to 2.9	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Week 24.
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Global score, Week 12 (n=28,13,0)	2.3 units on a scale Interval 1.4 to 3.0	1.5 units on a scale Interval 1.0 to 2.5	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Week 24.
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Global score, Week 24 (n=26,7,10)	2.1 units on a scale Interval 1.6 to 2.5	1.3 units on a scale Interval 1.0 to 2.8	2.1 units on a scale Interval 1.4 to 2.7
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Dressing/grooming, Baseline (n=31,18,0)	2.0 units on a scale Interval 1.0 to 3.0	2.0 units on a scale Interval 1.0 to 3.0	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Week 24.
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Dressing/grooming, Week 12 (n=30,16,0)	2.0 units on a scale Interval 1.0 to 3.0	1.0 units on a scale Interval 0.0 to 3.0	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Week 24.
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Dressing/grooming, Week 24 (n=26,7,10)	2.0 units on a scale Interval 1.0 to 3.0	1.0 units on a scale Interval 1.0 to 3.0	2.0 units on a scale Interval 1.0 to 3.0
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Arising, Baseline (n=32,19,0)	2.0 units on a scale Interval 1.0 to 3.0	2.0 units on a scale Interval 1.0 to 3.0	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Week 24.
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Arising, Week 12 (n=30,17,0)	2.0 units on a scale Interval 0.0 to 3.0	1.0 units on a scale Interval 1.0 to 3.0	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Week 24.
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Arising, Week 24 (n=26,7,10)	2.0 units on a scale Interval 1.0 to 2.0	1.0 units on a scale Interval 1.0 to 3.0	2.0 units on a scale Interval 1.0 to 3.0
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Eating, Baseline (n=26,14,0)	3.0 units on a scale Interval 1.0 to 3.0	2.0 units on a scale Interval 1.0 to 3.0	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Week 24.
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Eating, Week 12 (n=27,10,0)	3.0 units on a scale Interval 2.0 to 3.0	2.0 units on a scale Interval 1.0 to 3.0	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Week 24.
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Eating, Week 24 (n=24,7,9)	3.0 units on a scale Interval 2.0 to 3.0	1.0 units on a scale Interval 1.0 to 3.0	2.0 units on a scale Interval 2.0 to 3.0
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Walking, Baseline (n=32,19,0)	2.0 units on a scale Interval 1.0 to 3.0	2.0 units on a scale Interval 1.0 to 3.0	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Week 24.
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Hygiene, Baseline (n=31,18,0)	2.0 units on a scale Interval 1.0 to 3.0	2.0 units on a scale Interval 1.0 to 3.0	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Week 24.
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Reach, Baseline (n=24,12,0)	3.0 units on a scale Interval 1.0 to 3.0	2.0 units on a scale Interval 1.0 to 3.0	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Week 24.
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Reach, Week 12 (n=26,10,0)	2.0 units on a scale Interval 0.0 to 3.0	2.0 units on a scale Interval 0.0 to 3.0	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Week 24.
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Reach, Week 24 (n=23,7,8)	2.0 units on a scale Interval 2.0 to 2.0	2.0 units on a scale Interval 1.0 to 3.0	2.5 units on a scale Interval 1.0 to 3.0
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Grip, Baseline (n=29,18,0)	2.0 units on a scale Interval 1.0 to 3.0	2.0 units on a scale Interval 1.0 to 3.0	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Week 24.
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Activity, Week 24 (n=25,7,8)	2.0 units on a scale Interval 2.0 to 2.0	1.0 units on a scale Interval 1.0 to 3.0	2.0 units on a scale Interval 2.0 to 3.0
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Walking, Week 12 (n=30,17,0)	2.0 units on a scale Interval 1.0 to 3.0	1.0 units on a scale Interval 0.0 to 3.0	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Week 24.
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Walking, Week 24 (n=26,7,10)	2.0 units on a scale Interval 2.0 to 3.0	1.0 units on a scale Interval 1.0 to 3.0	2.0 units on a scale Interval 1.0 to 3.0
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Grip, Week 12 (n=29,14,0)	2.0 units on a scale Interval 0.0 to 3.0	1.0 units on a scale Interval 0.0 to 3.0	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Week 24.
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Grip, Week 24 (n=26,7,9)	2.0 units on a scale Interval 2.0 to 3.0	1.0 units on a scale Interval 1.0 to 3.0	2.0 units on a scale Interval 2.0 to 3.0
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Activity, Baseline (n=31,15,0)	2.0 units on a scale Interval 2.0 to 3.0	2.0 units on a scale Interval 1.0 to 3.0	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Week 24.
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores Activity, Week 12 (n=29,14,0)	2.0 units on a scale Interval 0.0 to 3.0	2.0 units on a scale Interval 0.0 to 3.0	NA units on a scale Data for the Placebo group with recovery therapy were collected only at Week 24.

SECONDARY outcome

Timeframe: Week 12

Population: ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.

ESR is an inflammatory marker and is used to assess disease activity in rheumatoid arthritis (RA). A reduction in ESR indicates improvement.

Outcome measures

Measure	Placebo n=15 Participants 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.	Tocilizumab 8 mg/kg n=30 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Change From Baseline to Week 12 in Erythrocyte Sedimentation Rate (ESR)	2.0 mm/hr Interval -49.0 to 39.0	-19.0 mm/hr Interval -93.0 to 0.0	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT population

ESR is an inflammatory marker and is used to assess disease activity in RA. A reduction in ESR indicates improvement.

Outcome measures

Measure	Placebo n=6 Participants 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.	Tocilizumab 8 mg/kg n=24 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=9 Participants 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.
Change From Baseline to Week 24 in ESR	-9.0 mm/hr Interval -47.0 to 3.0	-20.0 mm/hr Interval -95.0 to 5.0	-27.0 mm/hr Interval -75.0 to -7.0

SECONDARY outcome

Timeframe: Week 12

Population: ITT population. After Week 12, participants receiving placebo could have been switched to tocilizumab.

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).

Outcome measures

Measure	Placebo n=15 Participants 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.	Tocilizumab 8 mg/kg n=29 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Change From Baseline to Week 12 in C-Reactive Protein (CRP)	-0.1 mg/dL Interval -3.9 to 2.5	-0.9 mg/dL Interval -8.0 to 0.0	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT population

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.

Outcome measures

Measure	Placebo n=5 Participants 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.	Tocilizumab 8 mg/kg n=24 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=5 Participants 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.
Change From Baseline to Week 24 in CRP	-0.2 mg/dL Interval -2.9 to -0.02	-1.2 mg/dL Interval -8.0 to 0.0	-0.6 mg/dL Interval -9.7 to 0.0

SECONDARY outcome

Timeframe: Week 12

Population: ITT population

Change in serum cortisol was determined as the difference in the scores at Baseline and Week 12.

Outcome measures

Measure	Placebo n=16 Participants 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.	Tocilizumab 8 mg/kg n=29 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Change From Baseline to Week 12 in Serum Cortisol	2.5 mg/dL Interval -31.6 to 119.3	-1.4 mg/dL Interval -53.0 to 102.3	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT population;

Change in serum cortisol was determined as the difference in the scores at Baseline and Week 24.

Outcome measures

Measure	Placebo n=7 Participants 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.	Tocilizumab 8 mg/kg n=25 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=10 Participants 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.
Change From Baseline to Week 24 in Serum Cortisol	-5.2 mg/dL Interval -32.0 to 6.0	-2.5 mg/dL Interval -40.1 to 51.8	-5.1 mg/dL Interval -63.2 to 106.2

SECONDARY outcome

Timeframe: Week 12

Population: ITT population

Change in Plasma ACTH was determined as the difference in the scores at Baseline and Week 12.

Outcome measures

Measure	Placebo n=15 Participants 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.	Tocilizumab 8 mg/kg n=28 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Change From Baseline to Week 12 in Plasma Adrenocorticotrophic Hormone (ACTH)	0.00 mg/dL Interval -7.62 to 4.67	0.00 mg/dL Interval -10.27 to 7.41	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT population

Change in plasma ACTH was determined as the difference in the scores at baseline and Week 24.

Outcome measures

Measure	Placebo n=6 Participants 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.	Tocilizumab 8 mg/kg n=24 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=10 Participants 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.
Change From Baseline to Week 24 in Plasma ACTH	-0.3 mg/dL Interval -2.0 to 0.0	-0.4 mg/dL Interval -13.7 to 12.7	0.8 mg/dL Interval -1.9 to 4.1

SECONDARY outcome

Timeframe: Week 12

Population: ITT population

Change in serum androstenedione was determined as the difference in the scores at Baseline and Week 12.

Outcome measures

Measure	Placebo n=16 Participants 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.	Tocilizumab 8 mg/kg n=28 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Change From Baseline to Week 12 in Serum Androstenedione	0.01 mg/dL Interval -0.12 to 0.18	0.01 mg/dL Interval -0.57 to 0.29	—

SECONDARY outcome

Timeframe: Week 12

Population: ITT population

Change in 17OHP was determined as the difference in the scores at Baseline and Week 12.

Outcome measures

Measure	Placebo n=15 Participants 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.	Tocilizumab 8 mg/kg n=28 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Change From Baseline to Week 12 in 17 Hydroxy Progesterone (17OHP)	-0.03 mg/dL Interval -0.6 to 0.12	-0.01 mg/dL Interval -1.9 to 1.86	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT population

Change in serum androstenedione was determined as the difference in the scores at Baseline and Week 24.

Outcome measures

Measure	Placebo n=6 Participants 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.	Tocilizumab 8 mg/kg n=25 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=10 Participants 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.
Change From Baseline to Week 24 in Serum Androstenedione	0.01 mg/dL Interval -0.1 to 0.06	0.02 mg/dL Interval -1.56 to 0.7	-0.002 mg/dL Interval -0.71 to 0.36

SECONDARY outcome

Timeframe: Week 24

Population: ITT population

Change in 17OHP was determined as the difference in the scores at Baseline and Week 24.

Outcome measures

Measure	Placebo n=6 Participants 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.	Tocilizumab 8 mg/kg n=23 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=10 Participants 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.
Change From Baseline to Week 24 in 17OHP	-0.07 mg/dL Interval -0.86 to 0.46	-0.01 mg/dL Interval -1.97 to 1.03	-0.02 mg/dL Interval -0.5 to 0.2

SECONDARY outcome

Timeframe: Week 12

Population: ITT population

Change in DHEA was determined as the difference in the scores at Baseline and Week 12.

Outcome measures

Measure	Placebo n=15 Participants 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.	Tocilizumab 8 mg/kg n=28 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Change From Baseline to Week 12 in Serum Dehydroepiandrosterone (DHEA)	0.00 mg/dL Interval -5.87 to 4.03	-0.07 mg/dL Interval -6.09 to 2.9	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT population

Change in DHEA was determined as the difference in the scores at Baseline and Week 24.

Outcome measures

Measure	Placebo n=6 Participants 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.	Tocilizumab 8 mg/kg n=24 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=10 Participants 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.
Change From Baseline to Week 24 in Serum DHEA	-0.73 mg/dL Interval -3.45 to 2.5	0.17 mg/dL Interval -5.67 to 4.07	0.40 mg/dL Interval -10.43 to 3.38

SECONDARY outcome

Timeframe: Week 12

Population: ITT population

Change in Neuropeptide Y was determined as the difference in the scores at Baseline and Week 12.

Outcome measures

Measure	Placebo n=16 Participants 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.	Tocilizumab 8 mg/kg n=29 Participants 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).	Placebo-Tocilizumab 8 mg/kg 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.
Change From Baseline to Week 12 in Neuropeptide Y	-0.7 mg/dL Interval -45.4 to 51.2	-13.3 mg/dL Interval -91.4 to 60.3	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT population

Change in Neuropeptide Y was determined as the difference in the scores at Baseline and Week 24.

Outcome measures

Measure	Placebo n=6 Participants 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.	Tocilizumab 8 mg/kg n=24 Participants 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).	Placebo-Tocilizumab 8 mg/kg n=9 Participants 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.
Change From Baseline to Week 24 in Neuropeptide Y	-2.5 mg/dL Interval -44.5 to 58.4	-11.1 mg/dL Interval -80.8 to 80.6	-13.9 mg/dL Interval -52.8 to 28.2

Adverse Events

Tocilizumab 8 mg/kg

Serious events: 2 serious events

Other events: 29 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo-Tocilizumab 8 mg/kg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tocilizumab 8 mg/kg n=35 participants at risk 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).	Placebo n=10 participants at risk 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.	Placebo-Tocilizumab 8 mg/kg n=9 participants at risk 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.
Infections and infestations Cellulitis	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gluteal cleft cyst	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.

Other adverse events

Measure	Tocilizumab 8 mg/kg n=35 participants at risk 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).	Placebo n=10 participants at risk 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.	Placebo-Tocilizumab 8 mg/kg n=9 participants at risk 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.
Hepatobiliary disorders Hepatotoxicity	5.7% 2/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	20.0% 2/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Investigations Hypercholesterolemia	8.6% 3/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	10.0% 1/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	11.1% 1/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Infections and infestations Urinary Tract infection	11.4% 4/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	10.0% 1/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Skin and subcutaneous tissue disorders Malar rash	0.00% 0/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	10.0% 1/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Infections and infestations Oral candidiasis	0.00% 0/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	10.0% 1/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Hepatobiliary disorders Hepatic toxicity	5.7% 2/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	20.0% 2/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Investigations Abnormal liver function tests	0.00% 0/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	10.0% 1/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Investigations Liver Enzyme Elevation	5.7% 2/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Investigations Elevated ALT	5.7% 2/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Investigations Transaminase Elevation	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Investigations Bilirubin Elevation	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
General disorders Back pain	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Gastrointestinal disorders Blood Diarrhea	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
General disorders Cough	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	11.1% 1/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Investigations Dislipidemia	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Skin and subcutaneous tissue disorders Eczema	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Gastrointestinal disorders Epigastric pain	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Nervous system disorders Facial paralysis on the right side	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
General disorders Fall	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
General disorders Finger cut	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Infections and infestations Flu	5.7% 2/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Blood and lymphatic system disorders Hematoma cyclid of the right eye	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Infections and infestations Herpes simplex in the lips	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
General disorders Hoarseness	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Investigations Hypertriglyceridemia	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Infections and infestations Impetigo	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Infections and infestations Infected traumatic right leg ulcer	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
General disorders Inter-digital wound	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
General disorders Left leg cellulitis	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	10.0% 1/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leg ulcer	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Renal and urinary disorders Mild renal failure	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
General disorders Nausea	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Blood and lymphatic system disorders Neutropenia	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oral aftosis	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Infections and infestations Pharyngitis	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Skin and subcutaneous tissue disorders Rash	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
General disorders Tooth ache	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Infections and infestations Upper airways infection	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Infections and infestations Vaginal labial folliculitis	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Gastrointestinal disorders Vomiting	2.9% 1/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Blood and lymphatic system disorders Anemia	0.00% 0/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	10.0% 1/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
General disorders Flu-like syndrome	0.00% 0/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	10.0% 1/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	11.1% 1/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Investigations Nitritis Elevation	0.00% 0/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	10.0% 1/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
General disorders Odynophagia	0.00% 0/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	10.0% 1/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Blood and lymphatic system disorders Urine Leukocyte elevation	0.00% 0/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	10.0% 1/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Blood and lymphatic system disorders Varicose vein rupture	0.00% 0/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	10.0% 1/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Gastrointestinal disorders Diarrhea	0.00% 0/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	11.1% 1/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Gastrointestinal disorders Dyspepsia	0.00% 0/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	11.1% 1/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Gastrointestinal disorders Gastroenteritis	0.00% 0/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	11.1% 1/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
General disorders Gingivorrhagea in patient with low platelets	0.00% 0/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	11.1% 1/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
Infections and infestations Mouth mucositis	0.00% 0/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	11.1% 1/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.
General disorders Sputum	0.00% 0/35 • Adverse events were recorded from the day of screening until the end of study at Week 24.	0.00% 0/10 • Adverse events were recorded from the day of screening until the end of study at Week 24.	11.1% 1/9 • Adverse events were recorded from the day of screening until the end of study at Week 24.

Additional Information

Medical Communications

Hoffmann- LaRoche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER