Trial Outcomes & Findings for A Study of Tocilizumab in Combination With Disease-Modifying Anti-Rheumatic Drugs (DMARDs) in Participants With Moderate to Severe Active Rheumatoid Arthritis With an Inadequate Response to DMARDs (NCT NCT00996606)

Last Updated: 2017-06-19

Results Overview

Synovitis of the wrist was assessed at three sites including the radioulnar joint (RUJ), the radiocarpal joint (RCJ), and the intercarpal-carpometacarpal joints (IC-CMCJ). Global RAMRIS scores were assigned on a scale of 0 to 3 at each site, where 0 represented normal appearance with no synovial enhancement and each 1-point increase reflected one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. The scores for all three sites were added to give an aggregated score of 0 to 9. Baseline absolute value (AV) and change from Baseline to Week 4 were averaged among all participants, where negative changes indicated improvement in synovitis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

58 participants

Primary outcome timeframe

Baseline and Week 4

Results posted on

2017-06-19

Participant Flow

Participant milestones

Participant milestones
Measure	Tocilizumab in Active Rheumatoid Arthritis (RA) Participants with active RA received tocilizumab as 8 milligrams per kilogram (mg/kg) via intravenous (IV) infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Overall Study STARTED	58
Overall Study COMPLETED	50
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Tocilizumab in Active Rheumatoid Arthritis (RA) Participants with active RA received tocilizumab as 8 milligrams per kilogram (mg/kg) via intravenous (IV) infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Overall Study Adverse Event or Intercurrent Illness	2
Overall Study Insufficient Therapeutic Response	2
Overall Study Protocol Violation	1
Overall Study Withdrawal by Subject	3

Baseline Characteristics

A Study of Tocilizumab in Combination With Disease-Modifying Anti-Rheumatic Drugs (DMARDs) in Participants With Moderate to Severe Active Rheumatoid Arthritis With an Inadequate Response to DMARDs

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tocilizumab in Active RA n=58 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Age, Continuous	51.5 years STANDARD_DEVIATION 13.0 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 4

Population: ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who contributed to the endpoint. The number of participants who contributed to the analysis at each timepoint (n) is shown in the table.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=55 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Week 4 in Synovitis of the Wrist According to Rheumatoid Arthritis Magnetic Resonance Imaging (RAMRIS) Score Baseline AV (n=55)	5.78 units on a scale Standard Deviation 2.72
Change From Baseline to Week 4 in Synovitis of the Wrist According to Rheumatoid Arthritis Magnetic Resonance Imaging (RAMRIS) Score Week 4 (n=49)	-0.88 units on a scale Standard Deviation 1.56

PRIMARY outcome

Timeframe: Baseline and Week 4

RE was calculated as \[S0 minus (-) S55\] divided by (÷) S0, multiplied by (×) 100 percent (%), where S0 was defined as the signal noise ratio before contrast injection, and S55 was defined as the signal noise ratio 55 seconds after injection. Signal noise ratios were measured as the ratio between the signal in the region of interest and the standard deviation of background noise. Baseline AV and change from Baseline to Week 4 were averaged among all participants, where negative changes indicated improvement in synovitis.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=54 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Week 4 in Synovitis of the Wrist According to Relative Enhancement (RE) Before and After Contrast Injection Baseline AV (n=54)	99.25 percent relative enhancement Standard Deviation 57.85
Change From Baseline to Week 4 in Synovitis of the Wrist According to Relative Enhancement (RE) Before and After Contrast Injection Week 4 (n=45)	-0.48 percent relative enhancement Standard Deviation 47.85

PRIMARY outcome

Timeframe: Baseline and Week 4

REE per second was calculated as \[S55 - S0\] ÷ \[S0 × 55 seconds\] × 100%, where S0 was defined as the signal noise ratio before contrast injection, and S55 was defined as the signal noise ratio 55 seconds after injection. Signal noise ratios were measured as the ratio between the signal in the region of interest and the standard deviation of background noise. Baseline AV and change from Baseline to Week 4 were averaged among all participants, where negative changes indicated improvement in synovitis.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=54 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Week 4 in Synovitis of the Wrist According to Rate of Early Enhancement (REE) Per Second Before and After Contrast Injection Baseline AV (n=54)	1.19 percent rate of early enhancement Standard Deviation 1.04
Change From Baseline to Week 4 in Synovitis of the Wrist According to Rate of Early Enhancement (REE) Per Second Before and After Contrast Injection Week 4 (n=45)	-0.10 percent rate of early enhancement Standard Deviation 0.86

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 12, 24, 48

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=50 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to RAMRIS Score Week 2 (n=45)	-0.44 units on a scale Standard Deviation 1.03
Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to RAMRIS Score Week 12 (n=50)	-1.28 units on a scale Standard Deviation 1.96
Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to RAMRIS Score Week 24 (n=49)	-1.94 units on a scale Standard Deviation 2.34
Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to RAMRIS Score Week 48 (n=47)	-1.60 units on a scale Standard Deviation 2.42

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 12, 24, 48

RE was calculated as \[S0 - S55\] ÷ S0 × 100%, where S0 was defined as the signal noise ratio before contrast injection, and S55 was defined as the signal noise ratio 55 seconds after injection. Signal noise ratios were measured as the ratio between the signal in the region of interest and the standard deviation of background noise. The changes from Baseline to Weeks 2, 12, 24, and 48 were averaged among all participants, where negative changes indicated improvement in synovitis.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to RE Before and After Contrast Injection Week 24 (n=48)	-26.48 percent relative enhancement Standard Deviation 57.99
Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to RE Before and After Contrast Injection Week 2 (n=44)	5.80 percent relative enhancement Standard Deviation 46.14
Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to RE Before and After Contrast Injection Week 12 (n=49)	-9.27 percent relative enhancement Standard Deviation 50.07
Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to RE Before and After Contrast Injection Week 48 (n=45)	-19.74 percent relative enhancement Standard Deviation 74.08

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 12, 24, 48

REE per second was calculated as \[S55 - S0\] ÷ \[S0 × 55 seconds\] × 100%, where S0 was defined as the signal noise ratio before contrast injection, and S55 was defined as the signal noise ratio 55 seconds after injection. Signal noise ratios were measured as the ratio between the signal in the region of interest and the standard deviation of background noise. The changes from Baseline to Weeks 2, 12, 24, and 48 were averaged among all participants, where negative changes indicated improvement in synovitis.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to REE Per Second Before and After Contrast Injection Week 2 (n=44)	-0.04 percent rate of early enhancement Standard Deviation 1.11
Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to REE Per Second Before and After Contrast Injection Week 12 (n=49)	-0.48 percent rate of early enhancement Standard Deviation 0.96
Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to REE Per Second Before and After Contrast Injection Week 24 (n=48)	-0.57 percent rate of early enhancement Standard Deviation 0.87
Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to REE Per Second Before and After Contrast Injection Week 48 (n=45)	-0.66 percent rate of early enhancement Standard Deviation 1.24

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 12, 24, 48

Synovitis of the wrist was assessed at three sites including the RUJ, the RCJ, and the IC-CMCJ. Global RAMRIS scores were assigned on a scale of 0 to 3 at each site, where 0 represented normal appearance with no synovial enhancement and each 1-point increase reflected one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. The scores for all three sites were added to give an aggregated score of 0 to 9. Synovitis of MCP joints was determined on the basis of Short Inversion Time Inversion Recovery (STIR) sequence evaluation with modification of the RAMRIS score. Four MCP joint compartments were each assessed 0 to 3, so the aggregated MCP joint score ranged from 0 to 12. Combined synovitis in wrist and MCP joints was determined on the basis of STIR sequences to produce overall score from 0 to 21. Baseline AV and changes from Baseline to Weeks 2, 4, 12, 24, 48 were averaged among all participants, where negative changes indicated improvement in synovitis.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=55 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist Global Score, Baseline AV (n=55)	5.04 units on a scale Standard Deviation 2.24
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist Global Score, Week 2 (n=45)	-0.02 units on a scale Standard Deviation 1.70
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist Global Score, Week 4 (n=50)	-0.20 units on a scale Standard Deviation 1.50
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist Global Score, Week 12 (n=51)	-0.47 units on a scale Standard Deviation 2.07
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist Global Score, Week 24 (n=50)	-1.06 units on a scale Standard Deviation 2.11
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist Global Score, Week 48 (n=47)	-1.23 units on a scale Standard Deviation 2.28
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist Distal RUJ Score, Baseline AV (n=53)	1.62 units on a scale Standard Deviation 0.95
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist Distal RUJ Score, Week 2 (n=43)	-0.09 units on a scale Standard Deviation 0.78
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist Distal RUJ Score, Week 4 (n=48)	-0.15 units on a scale Standard Deviation 0.62
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist Distal RUJ Score, Week 12 (n=48)	-0.21 units on a scale Standard Deviation 0.87
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist Distal RUJ Score, Week 24 (n=48)	-0.44 units on a scale Standard Deviation 0.74
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist Distal RUJ Score, Week 48 (n=45)	-0.58 units on a scale Standard Deviation 0.94
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist Distal RCJ Score, Baseline AV (n=55)	1.73 units on a scale Standard Deviation 0.78
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist Distal RCJ Score, Week 2 (n=45)	0.11 units on a scale Standard Deviation 0.80
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist Distal RCJ Score, Week 4 (n=50)	-0.06 units on a scale Standard Deviation 0.62
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist Distal RCJ Score, Week 12 (n=51)	-0.12 units on a scale Standard Deviation 0.77
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist Distal RCJ Score, Week 24 (n=50)	-0.30 units on a scale Standard Deviation 0.91
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist Distal RCJ Score, Week 48 (n=47)	-0.38 units on a scale Standard Deviation 0.92
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist IC-CMCJ Score, Baseline AV (n=55)	1.75 units on a scale Standard Deviation 0.89
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist IC-CMCJ Score, Week 2 (n=44)	0.00 units on a scale Standard Deviation 0.72
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist IC-CMCJ Score, Week 4 (n=50)	0.00 units on a scale Standard Deviation 0.70
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist IC-CMCJ Score, Week 12 (n=51)	-0.22 units on a scale Standard Deviation 0.88
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist IC-CMCJ Score, Week 24 (n=50)	-0.40 units on a scale Standard Deviation 0.88
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist IC-CMCJ Score, Week 48 (n=47)	-0.34 units on a scale Standard Deviation 0.96
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score MCP STIR Joint Score, Baseline AV (n=54)	4.57 units on a scale Standard Deviation 3.10
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score MCP STIR Joint Score, Week 2 (n=40)	-0.13 units on a scale Standard Deviation 1.76
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score MCP STIR Joint Score, Week 4 (n=47)	-0.53 units on a scale Standard Deviation 1.90
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score MCP STIR Joint Score, Week 12 (n=45)	-0.53 units on a scale Standard Deviation 2.07
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score MCP STIR Joint Score, Week 24 (n=46)	-1.02 units on a scale Standard Deviation 2.24
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score MCP STIR Joint Score, Week 48 (n=44)	-1.25 units on a scale Standard Deviation 2.53
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist and MCP Aggregate Score, Baseline AV (n=56)	9.36 units on a scale Standard Deviation 4.49
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist and MCP Aggregate Score, Week 2 (n=46)	-0.54 units on a scale Standard Deviation 2.67
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist and MCP Aggregate Score, Week 4 (n=50)	-0.74 units on a scale Standard Deviation 2.62
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist and MCP Aggregate Score, Week 12 (n=51)	-1.33 units on a scale Standard Deviation 3.58
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist and MCP Aggregate Score, Week 24 (n=50)	-2.24 units on a scale Standard Deviation 3.54
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score Wrist and MCP Aggregate Score, Week 48 (n=47)	-2.49 units on a scale Standard Deviation 3.59

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 12, 24, 48

Erosion was evaluated at 15 sites in the wrist and 8 sites in the MCP joints. Bone erosion was scored on a scale of 0 to 10, where 0 represented no bone erosion and each 1-point increase reflected up to a 10% increase in extent of erosion. The number of bones with erosion was taken as the count of joints with a bone erosion score greater than or equal to (≥) 1. Baseline AV and changes from Baseline to Weeks 2, 4, 12, 24, and 48 were averaged among all participants, where negative changes indicated improvement in erosion.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=56 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Number of Bones With Erosion in the Wrist and MCP Joints Baseline AV (n=56)	8.07 bones with erosion Standard Deviation 4.71
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Number of Bones With Erosion in the Wrist and MCP Joints Week 2 (n=46)	-0.26 bones with erosion Standard Deviation 1.16
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Number of Bones With Erosion in the Wrist and MCP Joints Week 4 (n=50)	-0.16 bones with erosion Standard Deviation 1.04
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Number of Bones With Erosion in the Wrist and MCP Joints Week 12 (n=51)	-0.14 bones with erosion Standard Deviation 1.61
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Number of Bones With Erosion in the Wrist and MCP Joints Week 24 (n=50)	-0.06 bones with erosion Standard Deviation 1.82
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Number of Bones With Erosion in the Wrist and MCP Joints Week 48 (n=48)	-0.04 bones with erosion Standard Deviation 2.81

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 12, 24, 48

Erosion was evaluated at 15 sites in the wrist and 8 sites in the MCP joints. Bone erosion was scored on a scale of 0 to 10, where 0 represented no bone erosion and each 1-point increase reflected up to 10% increase in extent of erosion. Global RAMRIS scores were calculated as the sum of all joint sites for the wrist (range, 0 to 150) and MCP joints (range, 0 to 80). Aggregate wrist and MCP joint scores could range from 0 to 230 points. Baseline AV and changes from Baseline to Weeks 2, 4, 12, 24, and 48 were averaged among all participants, where negative changes indicated improvement in erosion.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=56 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score Wrist Score, Baseline AV (n=56)	7.32 units on a scale Standard Deviation 5.34
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score Wrist Score, Week 2 (n=46)	-0.24 units on a scale Standard Deviation 1.14
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score Wrist Score, Week 4 (n=50)	-0.16 units on a scale Standard Deviation 1.11
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score Wrist Score, Week 12 (n=51)	0.08 units on a scale Standard Deviation 1.40
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score Wrist Score, Week 24 (n=50)	0.28 units on a scale Standard Deviation 3.16
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score Wrist Score, Week 48 (n=47)	0.34 units on a scale Standard Deviation 3.67
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score MCP Score, Baseline AV (n=54)	4.26 units on a scale Standard Deviation 7.42
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score MCP Score, Week 2 (n=41)	-0.02 units on a scale Standard Deviation 0.88
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score MCP Score, Week 4 (n=47)	-0.04 units on a scale Standard Deviation 0.66
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score MCP Score, Week 12 (n=45)	0.04 units on a scale Standard Deviation 1.19
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score MCP Score, Week 24 (n=46)	-0.07 units on a scale Standard Deviation 1.65
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score MCP Score, Week 48 (n=44)	0.09 units on a scale Standard Deviation 1.18
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score Wrist and MCP Aggregate Score, Baseline AV (n=56)	11.43 units on a scale Standard Deviation 9.98
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score Wrist and MCP Aggregate Score, Week 2 (n=46)	-0.39 units on a scale Standard Deviation 1.86
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score Wrist and MCP Aggregate Score, Week 4 (n=50)	-0.24 units on a scale Standard Deviation 1.55
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score Wrist and MCP Aggregate Score, Week 12 (n=51)	-0.41 units on a scale Standard Deviation 3.14
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score Wrist and MCP Aggregate Score, Week 24 (n=50)	-0.18 units on a scale Standard Deviation 4.77
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score Wrist and MCP Aggregate Score, Week 48 (n=47)	0.36 units on a scale Standard Deviation 4.17

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 12, 24, 48

Edema was evaluated at 15 sites in the wrist and 8 sites in the MCP joints. Bone edema was scored on a scale of 0 to 3, where 0 represented no bone edema and each 1-point increase reflected one-third increase in extent of edema. The number of bones with edema was taken as the count of joints with a bone edema score greater than or equal to (≥) 1. Baseline AV and changes from Baseline to Weeks 2, 4, 12, 24, and 48 were averaged among all participants, where negative changes indicated improvement in edema.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=56 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Number of Bones With Bone Marrow Edema in the Wrist and MCP Joints Baseline AV (n=56)	7.91 bones with bone marrow edema Standard Deviation 6.27
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Number of Bones With Bone Marrow Edema in the Wrist and MCP Joints Week 2 (n=46)	-0.57 bones with bone marrow edema Standard Deviation 3.46
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Number of Bones With Bone Marrow Edema in the Wrist and MCP Joints Week 4 (n=50)	-0.78 bones with bone marrow edema Standard Deviation 3.51
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Number of Bones With Bone Marrow Edema in the Wrist and MCP Joints Week 12 (n=51)	-1.80 bones with bone marrow edema Standard Deviation 3.98
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Number of Bones With Bone Marrow Edema in the Wrist and MCP Joints Week 24 (n=50)	-2.56 bones with bone marrow edema Standard Deviation 4.13
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Number of Bones With Bone Marrow Edema in the Wrist and MCP Joints Week 48 (n=48)	-3.56 bones with bone marrow edema Standard Deviation 5.07

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 12, 24, 48

Edema was evaluated at 15 sites in the wrist and 8 sites in the MCP joints. Bone edema was scored on a scale of 0 to 3, where 0 represented no bone edema and each 1-point increase reflected one-third increase in extent of edema. Global RAMRIS scores were calculated as the sum of all joint sites for the wrist (range, 0 to 45) and MCP joints (range, 0 to 24). Aggregate wrist and MCP joint scores could range from 0 to 69 points. Baseline AV and changes from Baseline to Weeks 2, 4, 12, 24, and 48 were averaged among all participants, where negative changes indicated improvement in edema.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=56 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score Wrist Score, Baseline AV (n=56)	13.11 units on a scale Standard Deviation 12.88
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score Wrist Score, Week 2 (n=46)	-0.61 units on a scale Standard Deviation 6.23
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score Wrist Score, Week 4 (n=50)	-0.68 units on a scale Standard Deviation 5.87
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score Wrist Score, Week 12 (n=51)	-3.02 units on a scale Standard Deviation 8.55
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score Wrist Score, Week 24 (n=50)	-4.94 units on a scale Standard Deviation 10.80
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score Wrist Score, Week 48 (n=47)	-6.45 units on a scale Standard Deviation 11.90
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score MCP Score, Baseline AV (n=54)	3.17 units on a scale Standard Deviation 4.64
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score MCP Score, Week 2 (n=41)	-0.32 units on a scale Standard Deviation 3.66
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score MCP Score, Week 4 (n=47)	-0.89 units on a scale Standard Deviation 4.17
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score MCP Score, Week 12 (n=45)	-1.47 units on a scale Standard Deviation 4.01
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score MCP Score, Week 24 (n=46)	-1.70 units on a scale Standard Deviation 3.35
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score MCP Score, Week 48 (n=44)	-1.98 units on a scale Standard Deviation 4.13
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score Wrist and MCP Aggregate Score, Baseline AV (n=56)	16.16 units on a scale Standard Deviation 15.20
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score Wrist and MCP Aggregate Score, Week 2 (n=46)	-0.89 units on a scale Standard Deviation 7.71
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score Wrist and MCP Aggregate Score, Week 4 (n=50)	-1.52 units on a scale Standard Deviation 7.90
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score Wrist and MCP Aggregate Score, Week 12 (n=51)	-4.67 units on a scale Standard Deviation 9.29
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score Wrist and MCP Aggregate Score, Week 24 (n=50)	-6.70 units on a scale Standard Deviation 10.98
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score Wrist and MCP Aggregate Score, Week 48 (n=47)	-8.30 units on a scale Standard Deviation 13.06

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48

The TMSS was calculated as the sum of ES and JSNS and ranged from 0 to 202. The ES was taken as the sum of joint scores collected for 14 joints in each hand (individually scored from 0 to 7) and ranged from 0 to 98 for both hands. The JSNS was the sum of joint scores collected for 13 joints in each hand (individually scored from 0 to 8) and ranged from 0 to 104 for both hands. Scores of 0 reflected no change, while higher scores reflected increased disease activity. Baseline AV and changes from Baseline to Weeks 24 and 48 were averaged among all participants, where negative changes indicated improvement in disease activity.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=55 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 24 and 48 in Total Modified Sharp Score (TMSS), Erosion Score (ES), and Joint Space Narrowing Score (JSNS) TMSS, Baseline AV (n=55)	18.25 units on a scale Standard Deviation 26.37
Change From Baseline to Weeks 24 and 48 in Total Modified Sharp Score (TMSS), Erosion Score (ES), and Joint Space Narrowing Score (JSNS) TMSS, Week 24 (n=46)	0.41 units on a scale Standard Deviation 3.03
Change From Baseline to Weeks 24 and 48 in Total Modified Sharp Score (TMSS), Erosion Score (ES), and Joint Space Narrowing Score (JSNS) TMSS, Week 48 (n=47)	1.46 units on a scale Standard Deviation 5.66
Change From Baseline to Weeks 24 and 48 in Total Modified Sharp Score (TMSS), Erosion Score (ES), and Joint Space Narrowing Score (JSNS) ES, Baseline AV (n=55)	4.78 units on a scale Standard Deviation 11.85
Change From Baseline to Weeks 24 and 48 in Total Modified Sharp Score (TMSS), Erosion Score (ES), and Joint Space Narrowing Score (JSNS) ES, Week 24 (n=46)	0.05 units on a scale Standard Deviation 0.60
Change From Baseline to Weeks 24 and 48 in Total Modified Sharp Score (TMSS), Erosion Score (ES), and Joint Space Narrowing Score (JSNS) ES, Week 48 (n=47)	0.31 units on a scale Standard Deviation 1.07
Change From Baseline to Weeks 24 and 48 in Total Modified Sharp Score (TMSS), Erosion Score (ES), and Joint Space Narrowing Score (JSNS) JSNS, Baseline AV (n=55)	13.46 units on a scale Standard Deviation 17.39
Change From Baseline to Weeks 24 and 48 in Total Modified Sharp Score (TMSS), Erosion Score (ES), and Joint Space Narrowing Score (JSNS) JSNS, Week 24 (n=46)	0.36 units on a scale Standard Deviation 3.00
Change From Baseline to Weeks 24 and 48 in Total Modified Sharp Score (TMSS), Erosion Score (ES), and Joint Space Narrowing Score (JSNS) JSNS, Week 48 (n=47)	1.15 units on a scale Standard Deviation 5.42

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 12, 24, 48

Population: ITT Population. The number of participants who contributed to the analysis at each timepoint (n) is shown in the table.

The Ritchie Articular Index was scored on a scale of 0 to 3, according to the grades of tenderness in each of 26 assessed joints. The total score was taken as the sum of joint scores and ranged from 0 to 78. Scores of 0 reflected no tenderness, while higher scores reflected increased tenderness. Baseline AV and changes from Baseline to Weeks 2, 4, 12, 24, and 48 were averaged among all participants, where negative changes indicated improvement in joint tenderness.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=58 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Ritchie Articular Index Score Baseline AV (n=58)	16.69 units on a scale Standard Deviation 7.50
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Ritchie Articular Index Score Week 2 (n=53)	-4.85 units on a scale Standard Deviation 5.37
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Ritchie Articular Index Score Week 4 (n=54)	-7.06 units on a scale Standard Deviation 6.50
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Ritchie Articular Index Score Week 12 (n=52)	-9.37 units on a scale Standard Deviation 6.65
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Ritchie Articular Index Score Week 24 (n=53)	-11.60 units on a scale Standard Deviation 6.71
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Ritchie Articular Index Score Week 48 (n=54)	-12.09 units on a scale Standard Deviation 6.95

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 12, 24, 48

Perceived pain was assessed on a 0- to 100-millimeter (mm) VAS, where the distance from 0 mm represented the participant's self evaluation of pain (0 mm = no pain, 100 mm = maximum pain). Baseline AV and changes from Baseline to Weeks 2, 4, 12, 24, and 48 were averaged among all participants, where negative changes indicated a decrease in perceived pain.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=54 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived Pain According to Visual Analog Scale (VAS) Score Baseline AV (n=54)	57.69 mm Standard Deviation 24.07
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived Pain According to Visual Analog Scale (VAS) Score Week 2 (n=50)	-18.56 mm Standard Deviation 20.73
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived Pain According to Visual Analog Scale (VAS) Score Week 4 (n=51)	-20.57 mm Standard Deviation 22.44
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived Pain According to Visual Analog Scale (VAS) Score Week 12 (n=52)	-32.75 mm Standard Deviation 29.00
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived Pain According to Visual Analog Scale (VAS) Score Week 24 (n=50)	-35.36 mm Standard Deviation 24.62
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived Pain According to Visual Analog Scale (VAS) Score Week 48 (n=50)	-39.44 mm Standard Deviation 25.26

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 12, 24, 48

Global assessment of disease activity was performed using a 0- to 100-mm VAS, where the distance from 0 mm represented the investigator's evaluation or the participant's self evaluation of disease activity (0 mm = no disease activity, 100 mm = maximum disease activity). Baseline AV and changes from Baseline to Weeks 2, 4, 12, 24, and 48 were averaged among all participants, where negative changes indicated improvement in disease activity.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=55 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived General Health According to VAS Score Participant Evaluation, Baseline AV (n=55)	59.51 mm Standard Deviation 23.32
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived General Health According to VAS Score Participant Evaluation, Week 2 (n=50)	-19.58 mm Standard Deviation 20.75
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived General Health According to VAS Score Participant Evaluation, Week 4 (n=52)	-19.73 mm Standard Deviation 23.46
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived General Health According to VAS Score Participant Evaluation, Week 12 (n=53)	-32.64 mm Standard Deviation 28.59
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived General Health According to VAS Score Participant Evaluation, Week 24 (n=51)	-36.55 mm Standard Deviation 23.84
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived General Health According to VAS Score Participant Evaluation, Week 48 (n=51)	-40.41 mm Standard Deviation 25.69
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived General Health According to VAS Score Investigator Evaluation, Baseline AV (n=54)	58.89 mm Standard Deviation 16.26
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived General Health According to VAS Score Investigator Evaluation, Week 2 (n=47)	-19.21 mm Standard Deviation 16.71
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived General Health According to VAS Score Investigator Evaluation, Week 4 (n=51)	-27.55 mm Standard Deviation 20.49
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived General Health According to VAS Score Investigator Evaluation, Week 12 (n=51)	-37.61 mm Standard Deviation 21.63
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived General Health According to VAS Score Investigator Evaluation, Week 24 (n=50)	-43.94 mm Standard Deviation 19.55
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived General Health According to VAS Score Investigator Evaluation, Week 48 (n=50)	-44.72 mm Standard Deviation 18.98

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 12, 24, 48

Population: ITT Population. The number of participants who contributed to the analysis at each timepoint (n) is shown in the table.

The HAQ-DI assessed 20 items in eight functional activity domains including dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each item was scored on a scale of 0 to 3, where 0 represented activities performed without difficulty and 3 represented inability to perform activities alone. The total score was calculated as an average of all item scores, and thus also ranged from 0 to 3. Baseline AV and changes from Baseline to Weeks 2, 4, 12, 24, and 48 were averaged among all participants, where negative changes indicated an increase in ability to perform activities independently.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=58 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score Baseline AV (n=58)	1.33 units on a scale Standard Deviation 0.78
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score Week 2 (n=52)	-0.34 units on a scale Standard Deviation 0.51
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score Week 4 (n=53)	-0.35 units on a scale Standard Deviation 0.49
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score Week 12 (n=54)	-0.52 units on a scale Standard Deviation 0.68
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score Week 24 (n=53)	-0.61 units on a scale Standard Deviation 0.58
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score Week 48 (n=54)	-0.67 units on a scale Standard Deviation 0.61

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 12, 24, 48

Population: ITT Population. The number of participants who contributed to the analysis at each timepoint (n) is shown in the table.

The DAS28 was derived from assessments of C-reactive protein (CRP), tender joint count (TJC), swollen joint count (SJC), and general health according to 100-mm VAS. DAS28 scores were calculated as \[0.56 × square root of TJC\] plus (+) \[0.28 × square root of SJC\] + \[0.36 × natural log (CRP + 1)\] + \[0.014 × VAS\] + 0.96. TJC was defined as the number of painful joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. CRP was measured in milligrams per deciliter (mg/dL). DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. Baseline AV and changes from Baseline to Weeks 2, 4, 12, 24, and 48 were averaged among all participants, where negative changes indicated an improvement in disease activity.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=58 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Disease Activity Score of 28 Joints (DAS28) Score Baseline AV (n=58)	5.44 units on a scale Standard Deviation 0.90
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Disease Activity Score of 28 Joints (DAS28) Score Week 2 (n=50)	-1.22 units on a scale Standard Deviation 0.88
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Disease Activity Score of 28 Joints (DAS28) Score Week 4 (n=53)	-1.62 units on a scale Standard Deviation 1.05
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Disease Activity Score of 28 Joints (DAS28) Score Week 12 (n=53)	-2.29 units on a scale Standard Deviation 1.31
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Disease Activity Score of 28 Joints (DAS28) Score Week 24 (n=53)	-2.88 units on a scale Standard Deviation 1.17
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Disease Activity Score of 28 Joints (DAS28) Score Week 48 (n=53)	-3.07 units on a scale Standard Deviation 1.27

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 12, 24, 48

Level of VEGF was measured in picograms per milliliter (pg/mL). Baseline AV and changes from Baseline to Weeks 2, 4, 12, 24, and 48 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=53 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Vascular Endothelial Growth Factor (VEGF) Concentration Baseline AV (n=53)	154.37 pg/mL Standard Deviation 130.97
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Vascular Endothelial Growth Factor (VEGF) Concentration Week 2 (n=45)	-53.06 pg/mL Standard Deviation 145.81
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Vascular Endothelial Growth Factor (VEGF) Concentration Week 4 (n=48)	-63.61 pg/mL Standard Deviation 121.55
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Vascular Endothelial Growth Factor (VEGF) Concentration Week 12 (n=47)	-36.33 pg/mL Standard Deviation 189.04
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Vascular Endothelial Growth Factor (VEGF) Concentration Week 24 (n=45)	-66.10 pg/mL Standard Deviation 139.38
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Vascular Endothelial Growth Factor (VEGF) Concentration Week 48 (n=45)	-29.35 pg/mL Standard Deviation 183.46

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 12, 24, 48

ESR was measured in millimeters per hour (mm/h). Baseline AV and changes from Baseline to Weeks 2, 4, 12, 24, and 48 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=56 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erythrocyte Sedimentation Rate (ESR) Baseline AV (n=56)	37.39 mm/h Standard Deviation 23.79
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erythrocyte Sedimentation Rate (ESR) Week 2 (n=47)	-27.30 mm/h Standard Deviation 20.08
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erythrocyte Sedimentation Rate (ESR) Week 4 (n=52)	-27.63 mm/h Standard Deviation 21.17
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erythrocyte Sedimentation Rate (ESR) Week 12 (n=51)	-28.75 mm/h Standard Deviation 23.00
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erythrocyte Sedimentation Rate (ESR) Week 24 (n=50)	-30.58 mm/h Standard Deviation 22.96
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erythrocyte Sedimentation Rate (ESR) Week 48 (n=51)	-27.22 mm/h Standard Deviation 21.79

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 12, 24, 48

Population: ITT Population. The number of participants who contributed to the analysis at each timepoint (n) is shown in the table.

Level of hsCRP was measured in mg/dL. Baseline AV and changes from Baseline to Weeks 2, 4, 12, 24, and 48 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=58 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in High-Sensitivity C-Reactive Protein (hsCRP) Concentration Baseline AV (n=58)	14.43 mg/dL Standard Deviation 20.46
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in High-Sensitivity C-Reactive Protein (hsCRP) Concentration Week 2 (n=50)	-13.44 mg/dL Standard Deviation 21.56
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in High-Sensitivity C-Reactive Protein (hsCRP) Concentration Week 4 (n=53)	-11.96 mg/dL Standard Deviation 18.23
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in High-Sensitivity C-Reactive Protein (hsCRP) Concentration Week 12 (n=55)	-11.56 mg/dL Standard Deviation 22.51
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in High-Sensitivity C-Reactive Protein (hsCRP) Concentration Week 24 (n=53)	-13.43 mg/dL Standard Deviation 21.10
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in High-Sensitivity C-Reactive Protein (hsCRP) Concentration Week 48 (n=53)	-10.49 mg/dL Standard Deviation 12.31

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of sIL6R was measured in pg/mL. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=57 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Soluble Interleukin-6 Receptor (sIL6R) Level Baseline AV (n=57)	45270.8 pg/mL Standard Deviation 19965.0
Change From Baseline to Weeks 2 and 4 in Soluble Interleukin-6 Receptor (sIL6R) Level Week 2 (n=44)	332597.2 pg/mL Standard Deviation 264433.0
Change From Baseline to Weeks 2 and 4 in Soluble Interleukin-6 Receptor (sIL6R) Level Week 4 (n=50)	303037.2 pg/mL Standard Deviation 253261.4

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of mRNA for IL-17 (2\^ΔCt) was quantified by polymerase chain reaction (PCR). Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=51 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Messenger Ribonucleic Acid (mRNA) for Interleukin (IL)-17 (2^Delta Cycle Threshold [ΔCt]) Level Baseline AV (n=51)	0.0 2^ΔCt Standard Deviation 0.0
Change From Baseline to Weeks 2 and 4 in Messenger Ribonucleic Acid (mRNA) for Interleukin (IL)-17 (2^Delta Cycle Threshold [ΔCt]) Level Week 2 (n=37)	0.0 2^ΔCt Standard Deviation 0.0
Change From Baseline to Weeks 2 and 4 in Messenger Ribonucleic Acid (mRNA) for Interleukin (IL)-17 (2^Delta Cycle Threshold [ΔCt]) Level Week 4 (n=44)	0.0 2^ΔCt Standard Deviation 0.0

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of mRNA for IL-23 receptor (2\^ΔCt) was quantified by PCR. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=41 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in mRNA for IL-23 Receptor (2^ΔCt) Level Baseline AV (n=41)	0.224 2^ΔCt Standard Deviation 0.415
Change From Baseline to Weeks 2 and 4 in mRNA for IL-23 Receptor (2^ΔCt) Level Week 2 (n=31)	-0.007 2^ΔCt Standard Deviation 0.268
Change From Baseline to Weeks 2 and 4 in mRNA for IL-23 Receptor (2^ΔCt) Level Week 4 (n=35)	0.015 2^ΔCt Standard Deviation 0.495

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of ROR-γT (2\^ΔCt) was quantified by PCR. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=51 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in mRNA for RAR-Related Orphan Receptor (ROR)-γT (2^ΔCt) Level Baseline AV (n=51)	0.083 2^ΔCt Standard Deviation 0.269
Change From Baseline to Weeks 2 and 4 in mRNA for RAR-Related Orphan Receptor (ROR)-γT (2^ΔCt) Level Week 2 (n=37)	-0.027 2^ΔCt Standard Deviation 0.259
Change From Baseline to Weeks 2 and 4 in mRNA for RAR-Related Orphan Receptor (ROR)-γT (2^ΔCt) Level Week 4 (n=44)	-0.004 2^ΔCt Standard Deviation 0.310

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of mRNA for FOXP3 (2\^ΔCt) was quantified by PCR. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=51 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in mRNA for Forkhead Box Protein (FOXP) 3 (2^ΔCt) Level Baseline AV (n=51)	1.035 2^ΔCt Standard Deviation 2.509
Change From Baseline to Weeks 2 and 4 in mRNA for Forkhead Box Protein (FOXP) 3 (2^ΔCt) Level Week 2 (n=37)	-0.315 2^ΔCt Standard Deviation 1.446
Change From Baseline to Weeks 2 and 4 in mRNA for Forkhead Box Protein (FOXP) 3 (2^ΔCt) Level Week 4 (n=44)	-0.059 2^ΔCt Standard Deviation 1.615

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of CD4-positive cell infiltration was expressed as the percentage of PBMCs. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=51 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Cluster of Differentiation (CD) 4-Positive Cells as a Percentage of Peripheral Blood Mononuclear Cells (PBMCs) Baseline AV (n=51)	56.15 percentage of PBMCs Standard Deviation 12.63
Change From Baseline to Weeks 2 and 4 in Cluster of Differentiation (CD) 4-Positive Cells as a Percentage of Peripheral Blood Mononuclear Cells (PBMCs) Week 2 (n=29)	-1.47 percentage of PBMCs Standard Deviation 13.64
Change From Baseline to Weeks 2 and 4 in Cluster of Differentiation (CD) 4-Positive Cells as a Percentage of Peripheral Blood Mononuclear Cells (PBMCs) Week 4 (n=45)	0.77 percentage of PBMCs Standard Deviation 8.97

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The mean fluorescence intensity of CD4-positive cells was measured by flow cytometry. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=51 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in CD4 Mean Intensity of Fluorescence Baseline AV (n=51)	6970.94 fluorescence intensity units Standard Deviation 2725.05
Change From Baseline to Weeks 2 and 4 in CD4 Mean Intensity of Fluorescence Week 2 (n=29)	464.04 fluorescence intensity units Standard Deviation 3341.91
Change From Baseline to Weeks 2 and 4 in CD4 Mean Intensity of Fluorescence Week 4 (n=45)	-1139.29 fluorescence intensity units Standard Deviation 3024.58

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of CD25-positive cell infiltration was expressed as the percentage of PBMCs. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=51 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in CD25-Positive Cells as a Percentage of PBMCs Baseline AV (n=51)	7.27 percentage of PBMCs Standard Deviation 4.92
Change From Baseline to Weeks 2 and 4 in CD25-Positive Cells as a Percentage of PBMCs Week 2 (n=28)	-0.95 percentage of PBMCs Standard Deviation 6.54
Change From Baseline to Weeks 2 and 4 in CD25-Positive Cells as a Percentage of PBMCs Week 4 (n=45)	0.04 percentage of PBMCs Standard Deviation 5.63

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The mean fluorescence intensity of CD25-positive cells was measured by flow cytometry. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=51 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in CD25 Mean Intensity of Fluorescence Baseline AV (n=51)	2326.25 fluorescence intensity units Standard Deviation 923.68
Change From Baseline to Weeks 2 and 4 in CD25 Mean Intensity of Fluorescence Week 2 (n=28)	74.76 fluorescence intensity units Standard Deviation 1850.13
Change From Baseline to Weeks 2 and 4 in CD25 Mean Intensity of Fluorescence Week 4 (n=45)	162.27 fluorescence intensity units Standard Deviation 632.62

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of CD45RO-positive cell infiltration was expressed as the percentage of PBMCs. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=50 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in CD45 "RO" Isoform (RO)-Positive Cells as a Percentage of PBMCs Baseline AV (n=50)	37.16 percentage of PBMCs Standard Deviation 11.50
Change From Baseline to Weeks 2 and 4 in CD45 "RO" Isoform (RO)-Positive Cells as a Percentage of PBMCs Week 2 (n=23)	1.77 percentage of PBMCs Standard Deviation 13.88
Change From Baseline to Weeks 2 and 4 in CD45 "RO" Isoform (RO)-Positive Cells as a Percentage of PBMCs Week 4 (n=45)	3.06 percentage of PBMCs Standard Deviation 11.65

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The mean fluorescence intensity of CD45RO-positive cells was measured by flow cytometry. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in CD45RO Mean Intensity of Fluorescence Baseline AV (n=49)	5138.47 fluorescence intensity units Standard Deviation 2184.11
Change From Baseline to Weeks 2 and 4 in CD45RO Mean Intensity of Fluorescence Week 2 (n=22)	-1779.59 fluorescence intensity units Standard Deviation 2088.51
Change From Baseline to Weeks 2 and 4 in CD45RO Mean Intensity of Fluorescence Week 4 (n=44)	-131.75 fluorescence intensity units Standard Deviation 1908.48

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of CCR6-positive cell infiltration was expressed as the percentage of PBMCs. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=27 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Cysteine-Cysteine Chemokine Receptor (CCR) 6-Positive Cells as a Percentage of PBMCs Baseline AV (n=27)	12.75 percentage of PBMCs Standard Deviation 6.40
Change From Baseline to Weeks 2 and 4 in Cysteine-Cysteine Chemokine Receptor (CCR) 6-Positive Cells as a Percentage of PBMCs Week 2 (n=19)	2.34 percentage of PBMCs Standard Deviation 7.06
Change From Baseline to Weeks 2 and 4 in Cysteine-Cysteine Chemokine Receptor (CCR) 6-Positive Cells as a Percentage of PBMCs Week 4 (n=16)	3.09 percentage of PBMCs Standard Deviation 6.76

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The mean fluorescence intensity of CCR6-positive cells was measured by flow cytometry. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=27 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in CCR6 Mean Intensity of Fluorescence Baseline AV (n=27)	4651.85 fluorescence intensity units Standard Deviation 1211.33
Change From Baseline to Weeks 2 and 4 in CCR6 Mean Intensity of Fluorescence Week 2 (n=19)	291.63 fluorescence intensity units Standard Deviation 1820.02
Change From Baseline to Weeks 2 and 4 in CCR6 Mean Intensity of Fluorescence Week 4 (n=16)	376.56 fluorescence intensity units Standard Deviation 1306.58

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of CCR4-positive cell infiltration was expressed as the percentage of PBMCs. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=27 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in CCR4-Positive Cells as a Percentage of PBMCs Baseline AV (n=27)	11.79 percentage of PBMCs Standard Deviation 5.45
Change From Baseline to Weeks 2 and 4 in CCR4-Positive Cells as a Percentage of PBMCs Week 2 (n=19)	-1.64 percentage of PBMCs Standard Deviation 4.01
Change From Baseline to Weeks 2 and 4 in CCR4-Positive Cells as a Percentage of PBMCs Week 4 (n=16)	0.35 percentage of PBMCs Standard Deviation 3.11

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The mean fluorescence intensity of CCR4-positive cells was measured by flow cytometry. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=27 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in CCR4 Mean Intensity of Fluorescence Baseline AV (n=27)	2534.67 fluorescence intensity units Standard Deviation 570.00
Change From Baseline to Weeks 2 and 4 in CCR4 Mean Intensity of Fluorescence Week 2 (n=19)	262.95 fluorescence intensity units Standard Deviation 755.79
Change From Baseline to Weeks 2 and 4 in CCR4 Mean Intensity of Fluorescence Week 4 (n=16)	273.19 fluorescence intensity units Standard Deviation 687.01

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of IL-23Rp19-positive cell infiltration was expressed as the percentage of PBMCs. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=27 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in IL-23 Receptor p19 Subunit (IL-23Rp19)-Positive Cells as a Percentage of PBMCs Baseline AV (n=27)	1.10 percentage of PBMCs Standard Deviation 1.19
Change From Baseline to Weeks 2 and 4 in IL-23 Receptor p19 Subunit (IL-23Rp19)-Positive Cells as a Percentage of PBMCs Week 2 (n=19)	-0.32 percentage of PBMCs Standard Deviation 0.92
Change From Baseline to Weeks 2 and 4 in IL-23 Receptor p19 Subunit (IL-23Rp19)-Positive Cells as a Percentage of PBMCs Week 4 (n=16)	-0.34 percentage of PBMCs Standard Deviation 0.49

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The mean fluorescence intensity of IL-23Rp19-positive cells was measured by flow cytometry. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=27 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in IL-23Rp19 Mean Intensity of Fluorescence Baseline AV (n=27)	1416.30 fluorescence intensity units Standard Deviation 331.05
Change From Baseline to Weeks 2 and 4 in IL-23Rp19 Mean Intensity of Fluorescence Week 2 (n=19)	284.42 fluorescence intensity units Standard Deviation 1145.08
Change From Baseline to Weeks 2 and 4 in IL-23Rp19 Mean Intensity of Fluorescence Week 4 (n=16)	82.88 fluorescence intensity units Standard Deviation 552.61

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of Treg cell infiltration was expressed as the percentage of PBMCs. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=50 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Regulatory T (Treg) Cells as a Percentage of PBMCs Baseline AV (n=50)	2.03 percentage of PBMCs Standard Deviation 1.02
Change From Baseline to Weeks 2 and 4 in Regulatory T (Treg) Cells as a Percentage of PBMCs Week 2 (n=39)	-0.07 percentage of PBMCs Standard Deviation 0.86
Change From Baseline to Weeks 2 and 4 in Regulatory T (Treg) Cells as a Percentage of PBMCs Week 4 (n=42)	0.35 percentage of PBMCs Standard Deviation 1.41

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of Treg cell infiltration was expressed as the percentage of T cells. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=50 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Treg Cells as a Percentage of T Cells Baseline AV (n=50)	2.42 percentage of T cells Standard Deviation 1.18
Change From Baseline to Weeks 2 and 4 in Treg Cells as a Percentage of T Cells Week 2 (n=39)	-0.19 percentage of T cells Standard Deviation 0.98
Change From Baseline to Weeks 2 and 4 in Treg Cells as a Percentage of T Cells Week 4 (n=42)	0.44 percentage of T cells Standard Deviation 1.80

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The absolute number of Treg cells was expressed as cells per microliter (cells/mcL). Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Treg Cell Level Baseline AV (n=49)	34.51 cells/mcL Standard Deviation 18.35
Change From Baseline to Weeks 2 and 4 in Treg Cell Level Week 2 (n=35)	1.25 cells/mcL Standard Deviation 13.75
Change From Baseline to Weeks 2 and 4 in Treg Cell Level Week 4 (n=42)	6.30 cells/mcL Standard Deviation 34.60

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of Th17 cell infiltration was expressed as the percentage of PBMCs. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=27 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Helper T (Th) 17 Cells as a Percentage of PBMCs Baseline AV (n=27)	0.024 percentage of PBMCs Standard Deviation 0.036
Change From Baseline to Weeks 2 and 4 in Helper T (Th) 17 Cells as a Percentage of PBMCs Week 2 (n=18)	0.006 percentage of PBMCs Standard Deviation 0.059
Change From Baseline to Weeks 2 and 4 in Helper T (Th) 17 Cells as a Percentage of PBMCs Week 4 (n=16)	-0.002 percentage of PBMCs Standard Deviation 0.064

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of Th17 cell infiltration was expressed as the percentage of T cells. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=27 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Th17 Cells as a Percentage of T Cells Baseline AV (n=27)	0.031 percentage of T cells Standard Deviation 0.049
Change From Baseline to Weeks 2 and 4 in Th17 Cells as a Percentage of T Cells Week 2 (n=18)	-0.003 percentage of T cells Standard Deviation 0.076
Change From Baseline to Weeks 2 and 4 in Th17 Cells as a Percentage of T Cells Week 4 (n=16)	-0.007 percentage of T cells Standard Deviation 0.027

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The absolute number of Th17 cells was expressed as cells/mcL. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=27 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Th17 Cell Level Baseline AV (n=27)	0.295 cells/mcL Standard Deviation 0.368
Change From Baseline to Weeks 2 and 4 in Th17 Cell Level Week 2 (n=18)	0.050 cells/mcL Standard Deviation 0.344
Change From Baseline to Weeks 2 and 4 in Th17 Cell Level Week 4 (n=17)	-0.068 cells/mcL Standard Deviation 0.288

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of CD19-positive cell infiltration was expressed as the percentage of PBMCs. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in CD19-Positive Cells as a Percentage of PBMCs Baseline AV (n=49)	8.40 percentage of PBMCs Standard Deviation 4.68
Change From Baseline to Weeks 2 and 4 in CD19-Positive Cells as a Percentage of PBMCs Week 2 (n=1)	-4.80 percentage of PBMCs Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.
Change From Baseline to Weeks 2 and 4 in CD19-Positive Cells as a Percentage of PBMCs Week 4 (n=44)	-0.12 percentage of PBMCs Standard Deviation 6.39

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The mean fluorescence intensity of CD19-positive cells was measured by flow cytometry. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in CD19 Mean Intensity of Fluorescence Baseline AV (n=49)	19268.58 fluorescence intensity units Standard Deviation 5482.10
Change From Baseline to Weeks 2 and 4 in CD19 Mean Intensity of Fluorescence Week 2 (n=1)	-3656.00 fluorescence intensity units Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.
Change From Baseline to Weeks 2 and 4 in CD19 Mean Intensity of Fluorescence Week 4 (n=44)	251.34 fluorescence intensity units Standard Deviation 5251.35

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of CD24-positive cell infiltration was expressed as the percentage of PBMCs. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in CD24-Positive Cells as a Percentage of PBMCs Baseline AV (n=49)	8.02 percentage of PBMCs Standard Deviation 4.64
Change From Baseline to Weeks 2 and 4 in CD24-Positive Cells as a Percentage of PBMCs Week 2 (n=1)	-4.90 percentage of PBMCs Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.
Change From Baseline to Weeks 2 and 4 in CD24-Positive Cells as a Percentage of PBMCs Week 4 (n=44)	-0.73 percentage of PBMCs Standard Deviation 6.21

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The mean fluorescence intensity of CD24-positive cells was measured by flow cytometry. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in CD24 Mean Intensity of Fluorescence Week 2 (n=1)	1015.00 fluorescence intensity units Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.
Change From Baseline to Weeks 2 and 4 in CD24 Mean Intensity of Fluorescence Week 4 (n=44)	436.05 fluorescence intensity units Standard Deviation 1827.22
Change From Baseline to Weeks 2 and 4 in CD24 Mean Intensity of Fluorescence Baseline AV (n=49)	3133.63 fluorescence intensity units Standard Deviation 1652.36

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of CD27-positive cell infiltration was expressed as the percentage of PBMCs. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in CD27-Positive Cells as a Percentage of PBMCs Baseline AV (n=49)	57.51 percentage of PBMCs Standard Deviation 16.48
Change From Baseline to Weeks 2 and 4 in CD27-Positive Cells as a Percentage of PBMCs Week 2 (n=1)	-12.40 percentage of PBMCs Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.
Change From Baseline to Weeks 2 and 4 in CD27-Positive Cells as a Percentage of PBMCs Week 4 (n=44)	1.44 percentage of PBMCs Standard Deviation 12.22

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The mean fluorescence intensity of CD27-positive cells was measured by flow cytometry. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in CD27 Mean Intensity of Fluorescence Week 2 (n=1)	-349.00 fluorescence intensity units Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.
Change From Baseline to Weeks 2 and 4 in CD27 Mean Intensity of Fluorescence Week 4 (n=44)	-53.98 fluorescence intensity units Standard Deviation 390.89
Change From Baseline to Weeks 2 and 4 in CD27 Mean Intensity of Fluorescence Baseline AV (n=49)	1288.10 fluorescence intensity units Standard Deviation 302.90

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of CD38-positive cell infiltration was expressed as the percentage of PBMCs. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in CD38-Positive Cells as a Percentage of PBMCs Baseline AV (n=49)	49.51 percentage of PBMCs Standard Deviation 11.51
Change From Baseline to Weeks 2 and 4 in CD38-Positive Cells as a Percentage of PBMCs Week 2 (n=1)	-4.30 percentage of PBMCs Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.
Change From Baseline to Weeks 2 and 4 in CD38-Positive Cells as a Percentage of PBMCs Week 4 (n=44)	-0.78 percentage of PBMCs Standard Deviation 10.87

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The mean fluorescence intensity of CD38-positive cells was measured by flow cytometry. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in CD38 Mean Intensity of Fluorescence Baseline AV (n=49)	5746.98 fluorescence intensity units Standard Deviation 2082.63
Change From Baseline to Weeks 2 and 4 in CD38 Mean Intensity of Fluorescence Week 2 (n=1)	-193.00 fluorescence intensity units Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.
Change From Baseline to Weeks 2 and 4 in CD38 Mean Intensity of Fluorescence Week 4 (n=44)	162.66 fluorescence intensity units Standard Deviation 1602.09

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of IgM-positive cell infiltration was expressed as the percentage of PBMCs. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Immunoglobulin (Ig) M-Positive Cells as a Percentage of PBMCs Baseline AV (n=49)	17.06 percentage of PBMCs Standard Deviation 14.50
Change From Baseline to Weeks 2 and 4 in Immunoglobulin (Ig) M-Positive Cells as a Percentage of PBMCs Week 2 (n=1)	-3.60 percentage of PBMCs Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.
Change From Baseline to Weeks 2 and 4 in Immunoglobulin (Ig) M-Positive Cells as a Percentage of PBMCs Week 4 (n=44)	1.19 percentage of PBMCs Standard Deviation 11.61

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The mean fluorescence intensity of IgM-positive cells was measured by flow cytometry. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in IgM Mean Intensity of Fluorescence Baseline AV (n=49)	15545.94 fluorescence intensity units Standard Deviation 7231.80
Change From Baseline to Weeks 2 and 4 in IgM Mean Intensity of Fluorescence Week 2 (n=1)	-10381.0 fluorescence intensity units Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.
Change From Baseline to Weeks 2 and 4 in IgM Mean Intensity of Fluorescence Week 4 (n=44)	-56.45 fluorescence intensity units Standard Deviation 5681.03

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of mature B cell infiltration was expressed as the percentage of PBMCs. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Mature B Cells as a Percentage of PBMCs Baseline AV (n=49)	4.72 percentage of PBMCs Standard Deviation 3.56
Change From Baseline to Weeks 2 and 4 in Mature B Cells as a Percentage of PBMCs Week 2 (n=1)	-3.40 percentage of PBMCs Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.
Change From Baseline to Weeks 2 and 4 in Mature B Cells as a Percentage of PBMCs Week 4 (n=44)	-0.35 percentage of PBMCs Standard Deviation 4.24

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of mature B cell infiltration was expressed as the percentage of B cells. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Mature B Cells as a Percentage of B Cells Baseline AV (n=49)	48.58 percentage of B cells Standard Deviation 14.72
Change From Baseline to Weeks 2 and 4 in Mature B Cells as a Percentage of B Cells Week 2 (n=1)	-9.40 percentage of B cells Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.
Change From Baseline to Weeks 2 and 4 in Mature B Cells as a Percentage of B Cells Week 4 (n=44)	-0.11 percentage of B cells Standard Deviation 13.79

SECONDARY outcome

Timeframe: Baseline and Week 4

The absolute number of mature B cells was expressed as cells/mcL. Baseline AV and change from Baseline to Week 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=47 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Week 4 in Mature B Cell Level Baseline AV (n=47)	78.27 cells/mcL Standard Deviation 73.37
Change From Baseline to Week 4 in Mature B Cell Level Week 4 (n=42)	2.29 cells/mcL Standard Deviation 74.72

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of memory B cell infiltration was expressed as the percentage of PBMCs. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Memory B Cells as a Percentage of PBMCs Baseline AV (n=49)	1.49 percentage of PBMCs Standard Deviation 1.56
Change From Baseline to Weeks 2 and 4 in Memory B Cells as a Percentage of PBMCs Week 2 (n=1)	-0.90 percentage of PBMCs Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.
Change From Baseline to Weeks 2 and 4 in Memory B Cells as a Percentage of PBMCs Week 4 (n=44)	0.13 percentage of PBMCs Standard Deviation 1.28

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of memory B cell infiltration was expressed as the percentage of B cells. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Memory B Cells as a Percentage of B Cells Baseline AV (n=49)	18.95 percentage of B cells Standard Deviation 13.36
Change From Baseline to Weeks 2 and 4 in Memory B Cells as a Percentage of B Cells Week 2 (n=1)	4.30 percentage of B cells Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.
Change From Baseline to Weeks 2 and 4 in Memory B Cells as a Percentage of B Cells Week 4 (n=44)	0.62 percentage of B cells Standard Deviation 10.87

SECONDARY outcome

Timeframe: Baseline and Week 4

The absolute number of memory B cells was expressed as cells/mcL. Baseline AV and change from Baseline to Week 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=47 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Week 4 in Memory B Cell Level Baseline AV (n=47)	29.29 cells/mcL Standard Deviation 40.81
Change From Baseline to Week 4 in Memory B Cell Level Week 4 (n=42)	2.85 cells/mcL Standard Deviation 37.60

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of transitional B cell infiltration was expressed as the percentage of PBMCs. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Transitional B Cells as a Percentage of PBMCs Baseline AV (n=49)	0.58 percentage of PBMCs Standard Deviation 1.12
Change From Baseline to Weeks 2 and 4 in Transitional B Cells as a Percentage of PBMCs Week 2 (n=1)	0.00 percentage of PBMCs Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.
Change From Baseline to Weeks 2 and 4 in Transitional B Cells as a Percentage of PBMCs Week 4 (n=44)	-0.22 percentage of PBMCs Standard Deviation 1.21

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of transitional B cell infiltration was expressed as the percentage of B cells. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Transitional B Cells as a Percentage of B Cells Baseline AV (n=49)	5.26 percentage of B cells Standard Deviation 5.61
Change From Baseline to Weeks 2 and 4 in Transitional B Cells as a Percentage of B Cells Week 2 (n=1)	5.80 percentage of B cells Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.
Change From Baseline to Weeks 2 and 4 in Transitional B Cells as a Percentage of B Cells Week 4 (n=44)	-1.09 percentage of B cells Standard Deviation 4.54

SECONDARY outcome

Timeframe: Baseline and Week 4

The absolute number of transitional B cells was expressed as cells/mcL. Baseline AV and change from Baseline to Week 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=47 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Week 4 in Transitional B Cell Level Baseline AV (n=47)	6.70 cells/mcL Standard Deviation 7.79
Change From Baseline to Week 4 in Transitional B Cell Level Week 4 (n=42)	-0.62 cells/mcL Standard Deviation 7.51

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of plasma B cell infiltration was expressed as the percentage of PBMCs. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Plasma B Cells as a Percentage of PBMCs Baseline AV (n=49)	0.22 percentage of PBMCs Standard Deviation 0.57
Change From Baseline to Weeks 2 and 4 in Plasma B Cells as a Percentage of PBMCs Week 2 (n=1)	0.00 percentage of PBMCs Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.
Change From Baseline to Weeks 2 and 4 in Plasma B Cells as a Percentage of PBMCs Week 4 (n=44)	-0.08 percentage of PBMCs Standard Deviation 0.60

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

The intensity of plasma B cell infiltration was expressed as the percentage of B cells. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Plasma B Cells as a Percentage of B Cells Baseline AV (n=49)	1.52 percentage of B cells Standard Deviation 4.54
Change From Baseline to Weeks 2 and 4 in Plasma B Cells as a Percentage of B Cells Week 2 (n=1)	-0.20 percentage of B cells Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.
Change From Baseline to Weeks 2 and 4 in Plasma B Cells as a Percentage of B Cells Week 4 (n=44)	-0.06 percentage of B cells Standard Deviation 5.77

SECONDARY outcome

Timeframe: Baseline and Week 4

The absolute number of plasma B cells was expressed as cells/mcL. Baseline AV and change from Baseline to Week 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=47 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Week 4 in Plasma B Cell Level Baseline AV (n=47)	3.13 cells/mcL Standard Deviation 6.50
Change From Baseline to Week 4 in Plasma B Cell Level Week 4 (n=42)	-1.11 cells/mcL Standard Deviation 6.31

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of Th17CCL20 was measured in pg/mL. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=57 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Th17 Cysteine-Cysteine Chemokine Ligand (CCL) 20 Level Baseline AV (n=57)	35.03 pg/mL Standard Deviation 69.50
Change From Baseline to Weeks 2 and 4 in Th17 Cysteine-Cysteine Chemokine Ligand (CCL) 20 Level Week 2 (n=46)	2.57 pg/mL Standard Deviation 20.72
Change From Baseline to Weeks 2 and 4 in Th17 Cysteine-Cysteine Chemokine Ligand (CCL) 20 Level Week 4 (n=52)	-2.65 pg/mL Standard Deviation 23.18

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of Th17CCL20 was measured in pg/mL. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=56 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Th17CCL17 Level Baseline AV (n=56)	456.02 pg/mL Standard Deviation 404.17
Change From Baseline to Weeks 2 and 4 in Th17CCL17 Level Week 2 (n=45)	119.58 pg/mL Standard Deviation 453.39
Change From Baseline to Weeks 2 and 4 in Th17CCL17 Level Week 4 (n=51)	75.84 pg/mL Standard Deviation 333.43

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of BCA was measured in pg/mL. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=56 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in B Cell-Attracting Chemokine (BCA) Level Baseline AV (n=56)	122.28 pg/mL Standard Deviation 87.48
Change From Baseline to Weeks 2 and 4 in B Cell-Attracting Chemokine (BCA) Level Week 2 (n=45)	-21.37 pg/mL Standard Deviation 70.40
Change From Baseline to Weeks 2 and 4 in B Cell-Attracting Chemokine (BCA) Level Week 4 (n=51)	-18.26 pg/mL Standard Deviation 103.62

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of SDF1 was measured in pg/mL. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=57 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Stromal Cell-Derived Factor (SDF) 1 Level Baseline AV (n=57)	2151.47 pg/mL Standard Deviation 1133.79
Change From Baseline to Weeks 2 and 4 in Stromal Cell-Derived Factor (SDF) 1 Level Week 2 (n=46)	-1.85 pg/mL Standard Deviation 343.10
Change From Baseline to Weeks 2 and 4 in Stromal Cell-Derived Factor (SDF) 1 Level Week 4 (n=52)	-26.46 pg/mL Standard Deviation 390.80

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of BAFF was measured in pg/mL. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=57 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in B Cell-Activating Factor (BAFF) Level Baseline AV (n=57)	802.98 pg/mL Standard Deviation 317.98
Change From Baseline to Weeks 2 and 4 in B Cell-Activating Factor (BAFF) Level Week 2 (n=45)	28.04 pg/mL Standard Deviation 217.89
Change From Baseline to Weeks 2 and 4 in B Cell-Activating Factor (BAFF) Level Week 4 (n=52)	36.17 pg/mL Standard Deviation 223.64

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of APRIL was measured in pg/mL. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=57 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in A Proliferation-Inducing Ligand (APRIL) Level Baseline AV (n=57)	6807.49 pg/mL Standard Deviation 11178.42
Change From Baseline to Weeks 2 and 4 in A Proliferation-Inducing Ligand (APRIL) Level Week 2 (n=45)	-816.13 pg/mL Standard Deviation 4036.61
Change From Baseline to Weeks 2 and 4 in A Proliferation-Inducing Ligand (APRIL) Level Week 4 (n=51)	7.82 pg/mL Standard Deviation 3843.69

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of TNF-α was measured in pg/mL. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=55 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Tumor Necrosis Factor (TNF)-α Level Baseline AV (n=55)	2.285 pg/mL Standard Deviation 4.234
Change From Baseline to Weeks 2 and 4 in Tumor Necrosis Factor (TNF)-α Level Week 2 (n=42)	0.077 pg/mL Standard Deviation 1.228
Change From Baseline to Weeks 2 and 4 in Tumor Necrosis Factor (TNF)-α Level Week 4 (n=46)	0.254 pg/mL Standard Deviation 0.978

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of IL-1β was measured in pg/mL. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=37 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in IL-1β Level Baseline AV (n=37)	0.699 pg/mL Standard Deviation 0.692
Change From Baseline to Weeks 2 and 4 in IL-1β Level Week 2 (n=27)	-0.160 pg/mL Standard Deviation 0.598
Change From Baseline to Weeks 2 and 4 in IL-1β Level Week 4 (n=31)	-0.243 pg/mL Standard Deviation 0.620

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of IL-17 was measured in pg/mL. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=57 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in IL-17 Level Baseline AV (n=57)	15.00 pg/mL Standard Deviation 0.00
Change From Baseline to Weeks 2 and 4 in IL-17 Level Week 2 (n=47)	0.00 pg/mL Standard Deviation 0.00
Change From Baseline to Weeks 2 and 4 in IL-17 Level Week 4 (n=52)	0.00 pg/mL Standard Deviation 0.00

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of MCaP-1 was measured in pg/mL. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=57 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Monocyte Chemoattractant Protein (MCaP)-1 Level Baseline AV (n=57)	343.86 pg/mL Standard Deviation 283.29
Change From Baseline to Weeks 2 and 4 in Monocyte Chemoattractant Protein (MCaP)-1 Level Week 2 (n=47)	22.70 pg/mL Standard Deviation 143.82
Change From Baseline to Weeks 2 and 4 in Monocyte Chemoattractant Protein (MCaP)-1 Level Week 4 (n=51)	-33.20 pg/mL Standard Deviation 133.52

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of osteocalcin was measured in pg/mL. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=57 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Osteocalcin Level Baseline AV (n=57)	14069.60 pg/mL Standard Deviation 8770.17
Change From Baseline to Weeks 2 and 4 in Osteocalcin Level Week 2 (n=47)	-616.34 pg/mL Standard Deviation 6899.51
Change From Baseline to Weeks 2 and 4 in Osteocalcin Level Week 4 (n=52)	-99.00 pg/mL Standard Deviation 6938.56

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of Type I collagen N-propeptide was measured in pg/mL. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=57 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Type I Collagen N-Propeptide Level Baseline AV (n=57)	7731.89 pg/mL Standard Deviation 4625.23
Change From Baseline to Weeks 2 and 4 in Type I Collagen N-Propeptide Level Week 2 (n=46)	842.65 pg/mL Standard Deviation 4318.91
Change From Baseline to Weeks 2 and 4 in Type I Collagen N-Propeptide Level Week 4 (n=51)	-576.49 pg/mL Standard Deviation 4108.27

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of CTX-1 was measured in pg/mL. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=57 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in C-Terminal Telopeptide (CTX)-1 Level Baseline AV (n=57)	487.28 pg/mL Standard Deviation 248.61
Change From Baseline to Weeks 2 and 4 in C-Terminal Telopeptide (CTX)-1 Level Week 2 (n=48)	43.33 pg/mL Standard Deviation 193.11
Change From Baseline to Weeks 2 and 4 in C-Terminal Telopeptide (CTX)-1 Level Week 4 (n=50)	48.80 pg/mL Standard Deviation 233.25

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of ICTP was measured in pg/mL. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=57 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Type I Collagen C-Terminal Telopeptide (ICTP) Level Baseline AV (n=57)	6381.12 pg/mL Standard Deviation 2456.54
Change From Baseline to Weeks 2 and 4 in Type I Collagen C-Terminal Telopeptide (ICTP) Level Week 2 (n=48)	306.60 pg/mL Standard Deviation 1568.45
Change From Baseline to Weeks 2 and 4 in Type I Collagen C-Terminal Telopeptide (ICTP) Level Week 4 (n=51)	193.25 pg/mL Standard Deviation 1657.43

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of PIIANP was measured in pg/mL. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=57 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Type II Collagen N-Propeptide (PIIANP) Level Baseline AV (n=57)	1329158 pg/mL Standard Deviation 908163.5
Change From Baseline to Weeks 2 and 4 in Type II Collagen N-Propeptide (PIIANP) Level Week 2 (n=47)	-37518.8 pg/mL Standard Deviation 1008994
Change From Baseline to Weeks 2 and 4 in Type II Collagen N-Propeptide (PIIANP) Level Week 4 (n=51)	-69799.1 pg/mL Standard Deviation 673406.7

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4

Level of HELIX-II was measured in pg/mL. Baseline AV and changes from Baseline to Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=57 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2 and 4 in Type II Collagen Helical Peptide (HELIX-II) Level Baseline AV (n=57)	2521.12 pg/mL Standard Deviation 1960.76
Change From Baseline to Weeks 2 and 4 in Type II Collagen Helical Peptide (HELIX-II) Level Week 2 (n=48)	126.02 pg/mL Standard Deviation 1480.97
Change From Baseline to Weeks 2 and 4 in Type II Collagen Helical Peptide (HELIX-II) Level Week 4 (n=51)	-78.29 pg/mL Standard Deviation 1586.43

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 12, 24, 48

Population: ITT Population. The number of participants who contributed to the analysis at each timepoint (n) is shown in the table.

Level of Hb was measured in grams per liter (g/L). Baseline AV and changes from Baseline to Weeks 2, 4, 12, 24, and 48 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=58 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Hemoglobin (Hb) Concentration Week 12 (n=55)	4.31 g/L Standard Deviation 9.13
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Hemoglobin (Hb) Concentration Baseline AV (n=58)	128.28 g/L Standard Deviation 12.10
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Hemoglobin (Hb) Concentration Week 2 (n=50)	3.86 g/L Standard Deviation 5.87
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Hemoglobin (Hb) Concentration Week 4 (n=54)	2.09 g/L Standard Deviation 5.35
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Hemoglobin (Hb) Concentration Week 24 (n=53)	6.23 g/L Standard Deviation 8.99
Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Hemoglobin (Hb) Concentration Week 48 (n=53)	7.17 g/L Standard Deviation 8.28

SECONDARY outcome

Timeframe: Baseline; Day 2; and Weeks 2, 4

Level of STR was measured in pg/mL. Baseline AV and changes from Baseline to Day 2 and Weeks 2 and 4 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=57 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Day 2 and Weeks 2 and 4 in Soluble Transferrin Receptor (STR) Concentration Baseline AV (n=57)	4536413 pg/mL Standard Deviation 1336641
Change From Baseline to Day 2 and Weeks 2 and 4 in Soluble Transferrin Receptor (STR) Concentration Day 2 (n=10)	-83532.0 pg/mL Standard Deviation 446321.3
Change From Baseline to Day 2 and Weeks 2 and 4 in Soluble Transferrin Receptor (STR) Concentration Week 2 (n=46)	15712.17 pg/mL Standard Deviation 821775.0
Change From Baseline to Day 2 and Weeks 2 and 4 in Soluble Transferrin Receptor (STR) Concentration Week 4 (n=52)	-89722.7 pg/mL Standard Deviation 959232.1

SECONDARY outcome

Timeframe: Baseline and Week 48

IRE was approximated by parametric mapping via DYNAMIKA software and expressed as change in relative signal intensity per second (ΔI/sec). The mean of three different slices was used in the determination of IRE. Each slice consisted of a two-dimensional (2D) sequence of images acquired from the same physical location at different time instances. Baseline AV and change from Baseline to Week 48 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Week 48 in Initial Rate of Enhancement (IRE) by DYNAMIKA Software Analysis Baseline AV (n=49)	0.00503 ΔI/sec Standard Deviation 0.00371
Change From Baseline to Week 48 in Initial Rate of Enhancement (IRE) by DYNAMIKA Software Analysis Week 48 (n=32)	-0.00246 ΔI/sec Standard Deviation 0.00363

SECONDARY outcome

Timeframe: Baseline and Week 48

ME was approximated by parametric mapping via DYNAMIKA software and expressed as ratio of signal enhancement before and after contrast injection. The mean of three different slices was used in the determination of ME. Each slice consisted of a 2D sequence of images acquired from the same physical location at different time instances. Baseline AV and change from Baseline to Week 48 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Week 48 in Maximum Enhancement (ME) by DYNAMIKA Software Analysis Baseline AV (n=49)	1.606 ratio Standard Deviation 0.422
Change From Baseline to Week 48 in Maximum Enhancement (ME) by DYNAMIKA Software Analysis Week 48 (n=32)	-0.177 ratio Standard Deviation 0.416

SECONDARY outcome

Timeframe: Baseline and Week 48

Ntotal was approximated using DYNAMIKA software. The sum of three different slices was used in the determination of Ntotal. Each slice consisted of a 2D sequence of images acquired from the same physical location at different time instances. Baseline AV and change from Baseline to Week 48 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=48 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Week 48 in Number of Enhancing Voxels (Ntotal) by DYNAMIKA Software Analysis Baseline AV (n=48)	3155.69 enhancing voxels Standard Deviation 1677.22
Change From Baseline to Week 48 in Number of Enhancing Voxels (Ntotal) by DYNAMIKA Software Analysis Week 48 (n=31)	-974.16 enhancing voxels Standard Deviation 1606.14

SECONDARY outcome

Timeframe: Baseline and Week 48

Npersistent was approximated using DYNAMIKA software. The sum of three different slices was used in the determination of Npersistent. Each slice consisted of a 2D sequence of images acquired from the same physical location at different time instances. Baseline AV and change from Baseline to Week 48 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Week 48 in Number of Persistent Enhancing Voxels (Npersistent) by DYNAMIKA Software Analysis Baseline AV (n=49)	182.04 persistent enhancing voxels Standard Deviation 157.15
Change From Baseline to Week 48 in Number of Persistent Enhancing Voxels (Npersistent) by DYNAMIKA Software Analysis Week 48 (n=32)	-0.53 persistent enhancing voxels Standard Deviation 219.74

SECONDARY outcome

Timeframe: Baseline and Week 48

Nplateau was approximated using DYNAMIKA software. The sum of three different slices was used in the determination of Nplateau. Each slice consisted of a 2D sequence of images acquired from the same physical location at different time instances. Baseline AV and change from Baseline to Week 48 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Week 48 in Number of Plateau Enhancing Voxels (Nplateau) by DYNAMIKA Software Analysis Baseline AV (n=49)	1839.63 plateau enhancing voxels Standard Deviation 994.07
Change From Baseline to Week 48 in Number of Plateau Enhancing Voxels (Nplateau) by DYNAMIKA Software Analysis Week 48 (n=32)	-635.72 plateau enhancing voxels Standard Deviation 1019.13

SECONDARY outcome

Timeframe: Baseline and Week 48

Nwashout was approximated using DYNAMIKA software. The sum of three different slices was used in the determination of Nwashout. Each slice consisted of a 2D sequence of images acquired from the same physical location at different time instances. Baseline AV and change from Baseline to Week 48 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=49 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Week 48 in Number of Washout Enhancing Voxels (Nwashout) by DYNAMIKA Software Analysis Baseline AV (n=49)	1167.16 washout enhancing voxels Standard Deviation 783.19
Change From Baseline to Week 48 in Number of Washout Enhancing Voxels (Nwashout) by DYNAMIKA Software Analysis Week 48 (n=32)	-358.25 washout enhancing voxels Standard Deviation 798.88

SECONDARY outcome

Timeframe: Baseline and Week 48

Ntotal and IRE were approximated using DYNAMIKA software. The sum of three different slices was used in the determination of Ntotal. The mean of three different slices was used in the determination of IRE. Each slice consisted of a 2D sequence of images acquired from the same physical location at different time instances. Function of Ntotal×IRE was expressed as voxels times change in relative intensity per second (v\*ΔI/sec). Baseline AV and change from Baseline to Week 48 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=48 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Week 48 in Ntotal×IRE by DYNAMIKA Software Analysis Baseline AV (n=48)	6.01 v*ΔI/sec Standard Deviation 5.93
Change From Baseline to Week 48 in Ntotal×IRE by DYNAMIKA Software Analysis Week 48 (n=31)	-4.84 v*ΔI/sec Standard Deviation 6.13

SECONDARY outcome

Timeframe: Baseline and Week 48

Ntotal and ME were approximated using DYNAMIKA software. The sum of three different slices was used in the determination of Ntotal. The mean of three different slices was used in the determination of ME. Each slice consisted of a 2D sequence of images acquired from the same physical location at different time instances. Function of NtotalME was expressed as voxels times ratio of signal intensity before and after contrast injection (v\*ratio). Baseline AV and change from Baseline to Week 48 were averaged among all participants.

Outcome measures

Outcome measures
Measure	Tocilizumab in Active RA n=48 Participants Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Change From Baseline to Week 48 in Ntotal×ME by DYNAMIKA Software Analysis Baseline AV (n=48)	1882.40 v*ratio Standard Deviation 1267.48
Change From Baseline to Week 48 in Ntotal×ME by DYNAMIKA Software Analysis Week 48 (n=31)	-793.59 v*ratio Standard Deviation 1168.57

Adverse Events

Tocilizumab in Active RA

Serious events: 5 serious events

Other events: 50 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tocilizumab in Active RA n=58 participants at risk Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Cardiac disorders Tachycardia	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Upper limb fracture	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-hodgkin's lymphoma	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Renal and urinary disorders Renal colic	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Vascular disorders Hypertension	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.

Other adverse events

Other adverse events
Measure	Tocilizumab in Active RA n=58 participants at risk Participants with active RA received tocilizumab as 8 mg/kg via IV infusion every 4 weeks. A total of 12 infusions were given from Baseline to Week 44, and participants were assessed through Week 48.
Blood and lymphatic system disorders Anaemia	5.2% 3/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Blood and lymphatic system disorders Iron deficiency anaemia	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Blood and lymphatic system disorders Leukopenia	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Blood and lymphatic system disorders Neutropenia	13.8% 8/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Blood and lymphatic system disorders Splenomegaly	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Ear and labyrinth disorders Tinnitus	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Ear and labyrinth disorders Vertigo	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Eye disorders Eyelid oedema	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Eye disorders Xerophthalmia	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain lower	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Aphthous stomatitis	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Colitis	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Dysentery	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Enteritis	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Gastroenteritis	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrointestinal disorder	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Haematochezia	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Haemorrhoids	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Oropharyngeal pain	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Toothache	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
General disorders Asthenia	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
General disorders Chest pain	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
General disorders Face oedema	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
General disorders Hyperpyrexia	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
General disorders Pyrexia	5.2% 3/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
General disorders Swelling	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Hepatobiliary disorders Hepatic steatosis	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Hepatobiliary disorders Hypertransaminasaemia	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Bronchitis	8.6% 5/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Cystitis	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Escherichia infection	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Gastroenteritis	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Helicobacter gastritis	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Herpes ophthalmic	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Herpes simplex	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Herpes virus infection	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Herpes zoster	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Influenza	8.6% 5/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Labyrinthitis	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Localised infection	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Nail infection	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	12.1% 7/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Oral candidiasis	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Oral herpes	5.2% 3/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Pharyngitis	5.2% 3/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Tonsillitis	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Tracheitis	5.2% 3/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Eye injury	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Fracture	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Joint dislocation	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Limb injury	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Investigations Alanine aminotransferase increased	5.2% 3/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Investigations Blood cholesterol increased	5.2% 3/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Investigations Blood phosphorus increased	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Investigations Blood triglycerides increased	13.8% 8/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Investigations Eosinophil count increased	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Investigations Lipids increased	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Investigations Neutrophil count decreased	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Investigations Platelet count decreased	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Investigations Red blood cell sedimentation rate increased	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Investigations Transaminases increased	8.6% 5/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Investigations White blood cell count decreased	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypercholesterolaemia	19.0% 11/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypertriglyceridaemia	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	5.2% 3/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Bursitis	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Neck pain	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Nervous system disorders Carpal tunnel syndrome	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Nervous system disorders Dysaesthesia	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Nervous system disorders Headache	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Nervous system disorders Paraesthesia	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Nervous system disorders Presyncope	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Nervous system disorders Restless legs syndrome	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Nervous system disorders Sciatica	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Psychiatric disorders Anxiety	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Psychiatric disorders Depression	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Reproductive system and breast disorders Metrorrhagia	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Reproductive system and breast disorders Ovarian cyst	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	10.3% 6/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Productive cough	8.6% 5/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Throat irritation	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Eczema	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Erythema	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Papule	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash erythematous	5.2% 3/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Skin burning sensation	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Skin lesion	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Urticaria	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Urticaria papular	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Vascular disorders Flushing	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Vascular disorders Syncope	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Vascular disorders Hypertension	1.7% 1/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.
Cardiac disorders Tachycardia	3.4% 2/58 • Baseline to Week 48 Safety Population (same as ITT Population): All enrolled participants who received at least one dose of study drug.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

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 only after the first publication or presentation that involves the Overall Study. The 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