Trial Outcomes & Findings for An Extension to Study MA21573, Evaluating Tocilizumab in Patients With Active Rheumatoid Arthritis and an Inadequate Response to Current Non-Biological DMARDs and/or Anti-tumor Necrosis Factor (TNF) Therapy (NCT NCT00883753)

Last Updated: 2014-08-06

Results Overview

An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. The percentage of participants with AEs and SAEs that occurred in the Extension Study grouped according to the number of disease-modifying anti-rheumatic drugs (DMARD) a participant was taking at Core Baseline is presented.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

934 participants

Primary outcome timeframe

108 Weeks

Results posted on

2014-08-06

Participant Flow

Patients participated in the 24 Week Core Study: MA21573 \[NCT00750880\] then continued to receive tocilizumab in this extension study for total treatment time of up to 104 weeks + a 4 week follow-up.

Participant milestones

Participant milestones
Measure	Tocilizumab Participants received tocilizumab 8 mg/kg intravenous (IV), maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first.
Overall Study STARTED	934
Overall Study COMPLETED	827
Overall Study NOT COMPLETED	107

Reasons for withdrawal

Reasons for withdrawal
Measure	Tocilizumab Participants received tocilizumab 8 mg/kg intravenous (IV), maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first.
Overall Study Adverse Event	37
Overall Study Death	2
Overall Study Insufficient therapeutic response	16
Overall Study Lost to Follow-up	4
Overall Study Violation of selection criteria at entry	7
Overall Study Protocol Violation	2
Overall Study Refused treatment	4
Overall Study Withdrew consent	10
Overall Study Investigator's decision	17
Overall Study Administrative/Other	8

Baseline Characteristics

An Extension to Study MA21573, Evaluating Tocilizumab in Patients With Active Rheumatoid Arthritis and an Inadequate Response to Current Non-Biological DMARDs and/or Anti-tumor Necrosis Factor (TNF) Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tocilizumab n=934 Participants Participants received tocilizumab 8 mg/kg intravenous (IV), maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first.
Age, Continuous	54.3 years STANDARD_DEVIATION 12.02 • n=93 Participants
Sex: Female, Male Female	753 Participants n=93 Participants
Sex: Female, Male Male	181 Participants n=93 Participants

PRIMARY outcome

Timeframe: 108 Weeks

Population: LTE Safety population included all participants who received study drug and had at least one assessment of safety in the long term extension (LTE).

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=117 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD n=612 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD n=205 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	65.0 percentage of participants Interval 55.6 to 73.5	68.6 percentage of participants Interval 64.8 to 72.3	73.2 percentage of participants Interval 66.6 to 79.1
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	8.5 percentage of participants Interval 4.2 to 15.2	5.7 percentage of participants Interval 4.0 to 7.9	7.3 percentage of participants Interval 4.2 to 11.8

SECONDARY outcome

Timeframe: 108 Weeks

Population: LTE Safety population included all participants who received study drug and had at least one assessment of safety in the long term extension (LTE).

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Percentage of Participants With Adverse Events Leading to Withdraw	4.0 percentage of participants Interval 2.7 to 5.3	—	—

SECONDARY outcome

Timeframe: 108 Weeks

Population: LTE Safety population included all participants who received study drug and had at least one assessment of safety in the long term extension(LTE). Participants who did not experience an AE-related treatment discontinuation of tocilizumab were censored.

Time to withdrawal was defined as the number of days from Core Study Day 1 to the first date of onset of the AE leading to discontinuation of tocilizumab.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Time to Withdrawal Due to an Adverse Event (AE)	374.5 days Interval 286.0 to 441.0	—	—

SECONDARY outcome

Timeframe: 108 Weeks

Population: LTE Safety population included all participants who received study drug and had at least one assessment of safety in the long term extension (LTE).

Percentage of participants who discontinued treatment with tocilizumab for any reason.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Percentage of Participants With Discontinuation of Treatment Due to Any Cause	11.5 percentage of participants	—	—

SECONDARY outcome

Timeframe: 108 Weeks

Population: LTE Safety population included all participants who received study drug and had at least one assessment of safety in the long term extension (LTE). Participants who did not experience discontinuation of tocilizumab treatment were censored.

Time in days from start of the Core Study Day 1 to discontinuation of tocilizumab for any reason.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Time to Discontinuation of Tocilizumab Treatment for Any Cause	339.0 days Interval 294.0 to 370.0	—	—

SECONDARY outcome

Timeframe: 108 Weeks

Population: LTE Safety population included all participants who received study drug and had at least one assessment of safety in the long term extension (LTE).

Fasting blood samples were collected for Lipids: Cholesterol, Triglyceride, High-density lipoprotein (HDL) Cholesterol, Low-density lipoprotein (LDL) Cholesterol every 12 weeks and at follow-up in the Extension study and were sent to a central laboratory for analysis. Lipid abnormalities were defined as a High Cholesterol, High Triglyceride, Low HDL Cholesterol and a High LDL Cholesterol that occurred at any time in the extension study.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Percentage of Participants With Marked Lipid Abnormalities Cholesterol (high)	4.2 percentage of participants	—	—
Percentage of Participants With Marked Lipid Abnormalities HDL Cholesterol (low)	0.0 percentage of participants	—	—
Percentage of Participants With Marked Lipid Abnormalities LDL Cholesterol (high)	6.5 percentage of participants	—	—
Percentage of Participants With Marked Lipid Abnormalities Triglyceride (high)	14.9 percentage of participants	—	—

SECONDARY outcome

Timeframe: 108 Weeks

Population: LTE Safety population included all participants who received study drug and had at least one assessment of safety in the long term extension (LTE).

An Adverse Event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. Adverse Events of special interest for this study were: Infections (preferred term in the infection adverse event group term), Serious Infections (an infection that qualified as Serious Adverse Event), Infusion Reactions (occurred during infusion or within 24 hours of infusion), Major Cardiac AE (Myocardial Infarction/ Acute Coronary Syndrome), Stroke or Death.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Percentage of Participants With Adverse Events (AEs) of Special Interest Infusion Reaction	2.9 percentage of participants	—	—
Percentage of Participants With Adverse Events (AEs) of Special Interest Major Cardiac AE	0.3 percentage of participants	—	—
Percentage of Participants With Adverse Events (AEs) of Special Interest Stroke	0.9 percentage of participants	—	—
Percentage of Participants With Adverse Events (AEs) of Special Interest Death	0.3 percentage of participants	—	—
Percentage of Participants With Adverse Events (AEs) of Special Interest Infections	40.4 percentage of participants	—	—
Percentage of Participants With Adverse Events (AEs) of Special Interest Serious Infections	2.4 percentage of participants	—	—

SECONDARY outcome

Timeframe: 108 Weeks

Population: LTE Safety population included all participants who received study drug and had at least one assessment of safety in the long term extension (LTE).

Blood samples were collected for the Liver Function Test: Alanine aminotransferase (ALT) every 12 weeks and at the follow-up visit in the Extension study and were sent to a central laboratory for analysis. Percentage of participants with any values greater than 3 times the Upper Limit of Normal (3\*ULN) is reported. ULN= 55 Units/Liter.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Percentage of Participants With ALT Elevations > 3*ULN	1.9 percentage of participants	—	—

SECONDARY outcome

Timeframe: 108 Weeks

Population: LTE Safety population included all participants who received study drug and had at least one assessment of safety in the long term extension (LTE).

Blood was collected for the Liver Function Test: Aspartate aminotransferase (AST) every 12 weeks and at the follow-up visit in the Extension study and were sent to a central laboratory for analysis. Percentage of participants with any values greater than 3 times the Upper Limit of Normal (3\*ULN) is reported. ULN= 40 Units/Liter.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Percentage of Participants With AST Elevations > 3*ULN	0.4 percentage of participants	—	—

SECONDARY outcome

Timeframe: 108 Weeks

Population: Participants from the LTE Safety population included all participants who received study drug and had at least one assessment of safety in the long term extension (LTE) with data available for analysis.

Blood samples were collected for liver function test: Alanine aminotransferase (serum glutamic-pyruvic transaminase) \[ALT(SGPT)\] every 12 weeks and at the follow-up visit in the Extension study and were sent to a central laboratory for analysis. The Upper Limit of Normal (ULN) for ALT=55 Units/Liter. The number of participants categorized by the highest value for ALT/GPT during the study is reported: Normal (ALT result within the central lab reference range), Greater than the ULN to 1.5 times the ULN (\>ULN to 1.5\*ULN), 1.5 times the ULN to 3 times the ULN (1.5\*ULN to 3\*ULN) and 3 times the ULN to 5 times the ULN (3\*ULN to 5\*ULN).

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Number of Participants Categorized by Highest Value for ALT (SGPT) During the Study Normal	874 participants	—	—
Number of Participants Categorized by Highest Value for ALT (SGPT) During the Study >ULN - 1.5*ULN	50 participants	—	—
Number of Participants Categorized by Highest Value for ALT (SGPT) During the Study 1.5ULN to 3ULN	8 participants	—	—
Number of Participants Categorized by Highest Value for ALT (SGPT) During the Study 3ULN to 5ULN	2 participants	—	—

SECONDARY outcome

Timeframe: 108 Weeks

Blood samples were collected for liver function test: Aspartate aminotransferase (serum glutamic-oxaloacetic transaminase) \[AST (SGOT)\] every 12 weeks and at the follow-up visit in the Extension study and were sent to a central laboratory for analysis. The Upper Limit of Normal (ULN) for AST=40 Units/Liter. The number of participants categorized by worst value for AST(SGOT) during the study is reported: Normal (AST result is within the central lab reference range), Greater than the ULN to 1.5 times the ULN (\>ULN to 1.5\*ULN), 1.5 times the ULN to 3 times the ULN (1.5\*ULN to 3\*ULN) and 3 times the ULN to 5 times the ULN (3\*ULN to 5\*ULN).

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Number of Participants Categorized by Worst Value for AST (SGOT) During the Study 3ULN to 5ULN	1 participants	—	—
Number of Participants Categorized by Worst Value for AST (SGOT) During the Study Normal	903 participants	—	—
Number of Participants Categorized by Worst Value for AST (SGOT) During the Study >ULN to 1.5*ULN	26 participants	—	—
Number of Participants Categorized by Worst Value for AST (SGOT) During the Study 1.5ULN to 3ULN	4 participants	—	—

SECONDARY outcome

Timeframe: 108 Weeks

Population: Participants from the LTE Safety population (all participants who received study drug and had at least one assessment of safety in the long term extension) with data available for analysis.

Blood samples were collected for LDL Cholesterol every 12 weeks and at the follow-up visit in the Extension study and were sent to a central laboratory for analysis. The number of participants categorized by the worst value for LDL Cholesterol during the study is reported: Low is below central lab reference range, Normal is within the central lab reference range and High is above central lab reference range.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=933 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Number of Participants Categorized by Worst Value for LDL Cholesterol During the Study High	565 participants	—	—
Number of Participants Categorized by Worst Value for LDL Cholesterol During the Study Low	0 participants	—	—
Number of Participants Categorized by Worst Value for LDL Cholesterol During the Study Normal	368 participants	—	—

SECONDARY outcome

Timeframe: 108 Weeks

Blood samples were collected for Total Cholesterol every 12 weeks and at the follow-up visit in the Extension study and were sent to a central laboratory for analysis. The number of participants categorized by worst value for Total Cholesterol during the study is reported: Low is below central lab reference range, Normal is within the central lab reference range and High is above central lab reference range.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=933 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Number of Participants Categorized by Worst Value for Total Cholesterol During the Study Low	4 participants	—	—
Number of Participants Categorized by Worst Value for Total Cholesterol During the Study Normal	194 participants	—	—
Number of Participants Categorized by Worst Value for Total Cholesterol During the Study High	735 participants	—	—

SECONDARY outcome

Timeframe: 108 Weeks

Blood samples were collected for a Neutrophil Count every 12 weeks and at the follow-up visit in the Extension study and were sent to a central laboratory for analysis. The number of participants categorized by the worst value for Neutrophil Count during the study is reported: Low is below central lab reference range, Normal is within the central lab reference range and High is above central lab reference range.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=932 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Number of Participants Categorized by Worst Value for Neutrophil Count During the Study Normal	608 participants	—	—
Number of Participants Categorized by Worst Value for Neutrophil Count During the Study High	3 participants	—	—
Number of Participants Categorized by Worst Value for Neutrophil Count During the Study Low	321 participants	—	—

SECONDARY outcome

Timeframe: Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108

Population: Long Term Extension Intent-to-treat (LTE ITT) population included all participants from the Core Study who received at least one dose of study drug in the Extension Study. "n" in each of the categories is the number of participants with data available for both Baseline and the given time-point.

The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. Clinical meaningful improvement was defined as a ≥ 1.2 unit reduction in DAS28.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Percentage of Participants With Clinically Meaningful Improvement in Disease Activity Score-28 (DAS28) Week 48 (n=440)	96.6 percentage of participants	—	—
Percentage of Participants With Clinically Meaningful Improvement in Disease Activity Score-28 (DAS28) Week 60 (n=320)	97.8 percentage of participants	—	—
Percentage of Participants With Clinically Meaningful Improvement in Disease Activity Score-28 (DAS28) Week 12 (n=889)	94.7 percentage of participants	—	—
Percentage of Participants With Clinically Meaningful Improvement in Disease Activity Score-28 (DAS28) Week 24 (n=757)	94.8 percentage of participants	—	—
Percentage of Participants With Clinically Meaningful Improvement in Disease Activity Score-28 (DAS28) Week 36 (n=607)	96.4 percentage of participants	—	—
Percentage of Participants With Clinically Meaningful Improvement in Disease Activity Score-28 (DAS28) Week 72 (n=216)	96.8 percentage of participants	—	—
Percentage of Participants With Clinically Meaningful Improvement in Disease Activity Score-28 (DAS28) Week 84 (n=119)	95.8 percentage of participants	—	—
Percentage of Participants With Clinically Meaningful Improvement in Disease Activity Score-28 (DAS28) Week 96 (n=54)	100.0 percentage of participants	—	—
Percentage of Participants With Clinically Meaningful Improvement in Disease Activity Score-28 (DAS28) Week 108 (n=42)	100.0 percentage of participants	—	—

SECONDARY outcome

Timeframe: Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108

Population: LTE ITT population included all participants from the Core Study who received at least one dose of study drug in the Extension Study. "n" in each of the categories is the number of participants with data available at the given time-point.

The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. Low Disease Activity was defined as a score of \< 3.2.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Percentage of Participants With DAS28 Low Disease Activity Week 60 (n=320)	80.6 percentage of participants	—	—
Percentage of Participants With DAS28 Low Disease Activity Week 72 (n=216)	84.3 percentage of participants	—	—
Percentage of Participants With DAS28 Low Disease Activity Week 84 (n=119)	83.2 percentage of participants	—	—
Percentage of Participants With DAS28 Low Disease Activity Week 96 (n=54)	88.9 percentage of participants	—	—
Percentage of Participants With DAS28 Low Disease Activity Week 12 (n=891)	75.3 percentage of participants	—	—
Percentage of Participants With DAS28 Low Disease Activity Week 24 (n=759)	76.9 percentage of participants	—	—
Percentage of Participants With DAS28 Low Disease Activity Week 36 (n=609)	77.3 percentage of participants	—	—
Percentage of Participants With DAS28 Low Disease Activity Week 48 (n=440)	78.2 percentage of participants	—	—
Percentage of Participants With DAS28 Low Disease Activity Week 108 (n=42)	83.3 percentage of participants	—	—

SECONDARY outcome

Timeframe: Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108

The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission was defined as a DAS28 score \< 2.6.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Percentage of Participants With DAS28 Remission Week 24 (n=759)	61.9 percentage of participants	—	—
Percentage of Participants With DAS28 Remission Week 36 (n=609)	62.7 percentage of participants	—	—
Percentage of Participants With DAS28 Remission Week 48 (n=440)	62.7 percentage of participants	—	—
Percentage of Participants With DAS28 Remission Week 72 (n=216)	69.9 percentage of participants	—	—
Percentage of Participants With DAS28 Remission Week 84 (n=119)	68.9 percentage of participants	—	—
Percentage of Participants With DAS28 Remission Week 96 (n=54)	70.4 percentage of participants	—	—
Percentage of Participants With DAS28 Remission Week 108 (n=42)	71.4 percentage of participants	—	—
Percentage of Participants With DAS28 Remission Week 12 (n=891)	59.6 percentage of participants	—	—
Percentage of Participants With DAS28 Remission Week 60 (n=320)	65.9 percentage of participants	—	—

SECONDARY outcome

Timeframe: Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108

The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Change From Baseline in DAS28 Week 12 (n=889)	-3.58 score on a scale Standard Deviation 1.498	—	—
Change From Baseline in DAS28 Week 48 (n=440)	-3.80 score on a scale Standard Deviation 1.420	—	—
Change From Baseline in DAS28 Week 60 (n=320)	-3.91 score on a scale Standard Deviation 1.318	—	—
Change From Baseline in DAS28 Week 96 (n=54)	-4.14 score on a scale Standard Deviation 1.132	—	—
Change From Baseline in DAS28 Week 24 (n=757)	-3.62 score on a scale Standard Deviation 1.496	—	—
Change From Baseline in DAS28 Week 36 (n=607)	-3.74 score on a scale Standard Deviation 1.443	—	—
Change From Baseline in DAS28 Week 72 (n=216)	-3.93 score on a scale Standard Deviation 1.394	—	—
Change From Baseline in DAS28 Week 84 (n=119)	-3.94 score on a scale Standard Deviation 1.273	—	—
Change From Baseline in DAS28 Week 108 (n=42)	-4.12 score on a scale Standard Deviation 1.178	—	—

SECONDARY outcome

Timeframe: Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108

68 joints were assessed for tenderness and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Change From Baseline in Tender Joint Count Week 12 (n=927)	-17.45 joint count Standard Deviation 14.492	—	—
Change From Baseline in Tender Joint Count Week 24 (n=789)	-18.07 joint count Standard Deviation 14.524	—	—
Change From Baseline in Tender Joint Count Week 36 (n=627)	-18.592 joint count Standard Deviation 14.59	—	—
Change From Baseline in Tender Joint Count Week 48 (n=457)	-18.77 joint count Standard Deviation 14.744	—	—
Change From Baseline in Tender Joint Count Week 60 (n=334)	-19.16 joint count Standard Deviation 13.575	—	—
Change From Baseline in Tender Joint Count Week 72 (n=223)	-18.30 joint count Standard Deviation 13.157	—	—
Change From Baseline in Tender Joint Count Week 84 (n=121)	-17.45 joint count Standard Deviation 12.481	—	—
Change From Baseline in Tender Joint Count Week 96 (n=55)	-17.47 joint count Standard Deviation 11.445	—	—
Change From Baseline in Tender Joint Count Week 108 (n=43)	-17.35 joint count Standard Deviation 12.049	—	—

SECONDARY outcome

Timeframe: Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108

66 joints were assessed for swelling and joints were classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Change From Baseline in Swollen Joint Count Week 84 (n=121)	-9.90 joint count Standard Deviation 6.378	—	—
Change From Baseline in Swollen Joint Count Week 12 (n=927)	-10.16 joint count Standard Deviation 9.838	—	—
Change From Baseline in Swollen Joint Count Week 24 (n=789)	-10.17 joint count Standard Deviation 9.633	—	—
Change From Baseline in Swollen Joint Count Week 36 (n=627)	-10.55 joint count Standard Deviation 9.981	—	—
Change From Baseline in Swollen Joint Count Week 48 (n=457)	-10.78 joint count Standard Deviation 10.410	—	—
Change From Baseline in Swollen Joint Count Week 60 (n=334)	-10.83 joint count Standard Deviation 8.885	—	—
Change From Baseline in Swollen Joint Count Week 72 (n=223)	-10.91 joint count Standard Deviation 8.563	—	—
Change From Baseline in Swollen Joint Count Week 96 (n=55)	-8.62 joint count Standard Deviation 7.230	—	—
Change From Baseline in Swollen Joint Count Week 108 (n=43)	-8.58 joint count Standard Deviation 5.662	—	—

SECONDARY outcome

Timeframe: Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108

The patient assessed their pain using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Change From Baseline in Patient Assessment of Pain Visual Analog Scale (VAS) Week 48 (n=445)	-32.69 mm Standard Deviation 27.244	—	—
Change From Baseline in Patient Assessment of Pain Visual Analog Scale (VAS) Week 60 (n=326)	-35.35 mm Standard Deviation 26.082	—	—
Change From Baseline in Patient Assessment of Pain Visual Analog Scale (VAS) Week 72 (n=219)	-35.24 mm Standard Deviation 27.901	—	—
Change From Baseline in Patient Assessment of Pain Visual Analog Scale (VAS) Week 84 (n=119)	-35.71 mm Standard Deviation 25.901	—	—
Change From Baseline in Patient Assessment of Pain Visual Analog Scale (VAS) Week 96 (n=55)	-43.40 mm Standard Deviation 21.131	—	—
Change From Baseline in Patient Assessment of Pain Visual Analog Scale (VAS) Week 108 (n=42)	-45.48 mm Standard Deviation 20.956	—	—
Change From Baseline in Patient Assessment of Pain Visual Analog Scale (VAS) Week 12 (n=900)	-32.52 mm Standard Deviation 26.297	—	—
Change From Baseline in Patient Assessment of Pain Visual Analog Scale (VAS) Week 24 (n=772)	-32.59 mm Standard Deviation 25.998	—	—
Change From Baseline in Patient Assessment of Pain Visual Analog Scale (VAS) Week 36 (n=612)	-33.04 mm Standard Deviation 25.461	—	—

SECONDARY outcome

Timeframe: Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108

The patients global assessment of disease activity was assessed on a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Change From Baseline in Patient Global Assessment of Disease Activity VAS Week 12 (n=900)	-35.90 score on a scale Standard Deviation 25.964	—	—
Change From Baseline in Patient Global Assessment of Disease Activity VAS Week 24 (n=773)	-35.57 score on a scale Standard Deviation 25.368	—	—
Change From Baseline in Patient Global Assessment of Disease Activity VAS Week 36 (n=612)	-35.75 score on a scale Standard Deviation 25.853	—	—
Change From Baseline in Patient Global Assessment of Disease Activity VAS Week 48 (n=445)	-35.56 score on a scale Standard Deviation 27.475	—	—
Change From Baseline in Patient Global Assessment of Disease Activity VAS Week 60 (n=326)	-37.85 score on a scale Standard Deviation 26.723	—	—
Change From Baseline in Patient Global Assessment of Disease Activity VAS Week 72 (n=219)	-36.36 score on a scale Standard Deviation 26.828	—	—
Change From Baseline in Patient Global Assessment of Disease Activity VAS Week 84 (n=119)	-37.91 score on a scale Standard Deviation 27.628	—	—
Change From Baseline in Patient Global Assessment of Disease Activity VAS Week 96 (n=55)	-45.44 score on a scale Standard Deviation 21.766	—	—
Change From Baseline in Patient Global Assessment of Disease Activity VAS Week 108 (n=42)	-44.90 score on a scale Standard Deviation 28.689	—	—

SECONDARY outcome

Timeframe: Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108

The physician global assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Change From Baseline in Physician Global Assessment of Disease Activity VAS Week 12 (n=900)	-41.14 mm Standard Deviation 21.221	—	—
Change From Baseline in Physician Global Assessment of Disease Activity VAS Week 24 (n=769)	-40.86 mm Standard Deviation 21.114	—	—
Change From Baseline in Physician Global Assessment of Disease Activity VAS Week 36 (n=613)	-40.97 mm Standard Deviation 21.244	—	—
Change From Baseline in Physician Global Assessment of Disease Activity VAS Week 48 (n=447)	-42.20 mm Standard Deviation 21.551	—	—
Change From Baseline in Physician Global Assessment of Disease Activity VAS Week 60 (n=325)	-42.67 mm Standard Deviation 21.656	—	—
Change From Baseline in Physician Global Assessment of Disease Activity VAS Week 72 (n=217)	-43.74 mm Standard Deviation 20.941	—	—
Change From Baseline in Physician Global Assessment of Disease Activity VAS Week 84 (n=119)	-42.68 mm Standard Deviation 21.307	—	—
Change From Baseline in Physician Global Assessment of Disease Activity VAS Week 96 (n=55)	-43.60 mm Standard Deviation 17.828	—	—
Change From Baseline in Physician Global Assessment of Disease Activity VAS Week 108 (n=42)	-44.38 mm Standard Deviation 25.580	—	—

SECONDARY outcome

Timeframe: Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108

Blood was collected for Erythrocyte Sedimentation Rate (ESR) (a test that assesses tissue inflammation) and was analyzed at a local laboratory. ESR was measured in millimeters/hour (mm/hr). A reduction in the level is considered an improvement.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Week 60 (n=320)	-31.61 mm/hr Standard Deviation 22.864	—	—
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Week 72 (n=217)	-29.62 mm/hr Standard Deviation 21.904	—	—
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Week 84 (n=119)	-29.79 mm/hr Standard Deviation 19.525	—	—
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Week 96 (n=55)	-34.38 mm/hr Standard Deviation 18.865	—	—
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Week 108 (n=42)	-36.67 mm/hr Standard Deviation 17.167	—	—
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Week 12 (n=903)	-30.59 mm/hr Standard Deviation 24.839	—	—
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Week 24 (n=764)	-29.96 mm/hr Standard Deviation 24.584	—	—
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Week 36 (n=615)	-31.56 mm/hr Standard Deviation 24.293	—	—
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Week 48 (n=443)	-31.09 mm/hr Standard Deviation 24.408	—	—

SECONDARY outcome

Timeframe: Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108

Blood was collected for C-Reactive Protein (CRP) (a test for analysis of inflammatory and infectious disorders) and was analyzed at a central laboratory. The serum concentration of CRP was measured in milligrams/deciliter (mg/dL). A reduction in the level is considered an improvement.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Change From Baseline in C-Reactive Protein (CRP) Week 12 (n=904)	-1.72 mg/dL Standard Deviation 2.785	—	—
Change From Baseline in C-Reactive Protein (CRP) Week 24 (n=767)	-1.73 mg/dL Standard Deviation 2.620	—	—
Change From Baseline in C-Reactive Protein (CRP) Week 36 (n=611)	-1.79 mg/dL Standard Deviation 2.756	—	—
Change From Baseline in C-Reactive Protein (CRP) Week 48 (n=445)	-1.73 mg/dL Standard Deviation 2.696	—	—
Change From Baseline in C-Reactive Protein (CRP) Week 60 (n=319)	-1.82 mg/dL Standard Deviation 2.823	—	—
Change From Baseline in C-Reactive Protein (CRP) Week 72 (n=208)	-1.54 mg/dL Standard Deviation 2.609	—	—
Change From Baseline in C-Reactive Protein (CRP) Week 84 (n=112)	-1.56 mg/dL Standard Deviation 2.618	—	—
Change From Baseline in C-Reactive Protein (CRP) Week 96 (n=54)	-1.24 mg/dL Standard Deviation 1.999	—	—
Change From Baseline in C-Reactive Protein (CRP) Week 108 (n=43)	-0.98 mg/dL Standard Deviation 1.324	—	—

SECONDARY outcome

Timeframe: Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108

ACR20 response was defined as a ≥ 20 % improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Percentage of Participants With American College of Rheumatology 20 (ACR20) Response Week 24 (n=827)	75.1 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 20 (ACR20) Response Week 36 (n=685)	72.6 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 20 (ACR20) Response Week 48 (n=534)	69.1 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 20 (ACR20) Response Week 60 (n=419)	65.6 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 20 (ACR20) Response Week 72 (n=313)	60.7 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 20 (ACR20) Response Week 84 (n=217)	46.1 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 20 (ACR20) Response Week 12	76.1 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 20 (ACR20) Response Week 96 (n=154)	31.8 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 20 (ACR20) Response Week 108 (n=142)	28.2 percentage of participants	—	—

SECONDARY outcome

Timeframe: Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108

ACR50 response is defined as a ≥ 50 % improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Percentage of Participants With American College of Rheumatology 50 (ACR50) Response Week 48 (n=534)	48.5 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 50 (ACR50) Response Week 60 (n=419)	49.2 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 50 (ACR50) Response Week 72 (n=313)	46.0 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 50 (ACR50) Response Week 84 (n=217)	33.2 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 50 (ACR50) Response Week 96 (n=154)	26.6 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 50 (ACR50) Response Week 108 (n=142)	23.9 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 50 (ACR50) Response Week 12	56.3 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 50 (ACR50) Response Week 24 (n=827)	53.9 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 50 (ACR50) Response Week 36 (n=685)	53.6 percentage of participants	—	—

SECONDARY outcome

Timeframe: Core Baseline, Extension Weeks 12, 24, 36 ,48, 60, 72, 84, 96, 108

ACR70 response is defined as a ≥ 70 % improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Percentage of Participants With American College of Rheumatology 70 (ACR70) Response Week 12	31.4 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 70 (ACR70) Response Week 24 (n=827)	31.0 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 70 (ACR70) Response Week 36 (n=685)	32.6 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 70 (ACR70) Response Week 48 (n=534)	31.3 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 70 (ACR70) Response Week 60 (n=419)	28.2 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 70 (ACR70) Response Week 72 (n=313)	29.7 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 70 (ACR70) Response Week 84 (n=217)	23.5 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 70 (ACR70) Response Week 96 (n=154)	20.8 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 70 (ACR70) Response Week 108 (n=142)	17.6 percentage of participants	—	—

SECONDARY outcome

Timeframe: Core Baseline, Extension Weeks 12, 24, 36 ,48, 60, 72, 84, 96, 108

ACR90 response is defined as a ≥ 90 % improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Percentage of Participants With American College of Rheumatology 90 (ACR90) Response Week 12	9.9 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 90 (ACR90) Response Week 24 (n=827)	10.5 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 90 (ACR90) Response Week 36 (n=685)	12.0 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 90 (ACR90) Response Week 48 (n=534)	11.2 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 90 (ACR90) Response Week 60 (n=419)	11.0 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 90 (ACR90) Response Week 72 (n=313)	11.2 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 90 (ACR90) Response Week 84 (n=217)	11.5 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 90 (ACR90) Response Week 96 (n=154)	9.7 percentage of participants	—	—
Percentage of Participants With American College of Rheumatology 90 (ACR90) Response Week 108 (n=142)	9.2 percentage of participants	—	—

SECONDARY outcome

Timeframe: Core Baseline, Extension Weeks 12, 24, 36 ,48, 60, 72, 84, 96, 108

The Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis, consisting of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. There are 4 possible responses for each question: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty and 3=unable to do. The score for each of the domains is the highest (worst) score in each domain. A patient must have a domain score for at least 6 of 8 domains to calculate a valid HAQ-DI score which is the sum of domain scores, divided by the number of domains that have a score for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Response Week 12 (n=895)	-0.58 score on a scale Standard Deviation 0.605	—	—
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Response Week 24 (n=765)	-0.59 score on a scale Standard Deviation 0.611	—	—
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Response Week 36 (n=611)	-0.61 score on a scale Standard Deviation 0.607	—	—
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Response Week 48 (n=446)	-0.63 score on a scale Standard Deviation 0.595	—	—
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Response Week 60 (n=327)	-0.65 score on a scale Standard Deviation 0.614	—	—
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Response Week 72 (n=218)	-0.64 score on a scale Standard Deviation 0.610	—	—
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Response Week 84 (n=119)	-0.68 score on a scale Standard Deviation 0.650	—	—
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Response Week 96 (n=55)	-0.82 score on a scale Standard Deviation 0.582	—	—
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Response Week 108 (n=42)	-0.87 score on a scale Standard Deviation 0.634	—	—

SECONDARY outcome

Timeframe: Core Baseline, Extension Weeks 12, 24, 36 ,48, 60, 72, 84, 96, 108

The Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis, consisting of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. There are 4 possible responses for each question: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty and 3=unable to do. The score for each of the domains is the highest (worst) score in each domain. A patient must have a domain score for at least 6 of 8 domains to calculate a valid HAQ-DI score which is the sum of domain scores, divided by the number of domains that have a score for a total possible score minimum/maximum 0 (best) to 3 (worst). Clinically meaningful improvement is defined as a reduction from Baseline in the HAQ-DI score ≥ 0.2.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Percentage of Participants Achieving Clinical Meaningful Health Assessment Questionnaire Disability Index (HAQ-DI) Response Week 12 (n=895)	73.6 percentage of participants	—	—
Percentage of Participants Achieving Clinical Meaningful Health Assessment Questionnaire Disability Index (HAQ-DI) Response Week 24 (n=765)	73.9 percentage of participants	—	—
Percentage of Participants Achieving Clinical Meaningful Health Assessment Questionnaire Disability Index (HAQ-DI) Response Week 36 (n=611)	74.1 percentage of participants	—	—
Percentage of Participants Achieving Clinical Meaningful Health Assessment Questionnaire Disability Index (HAQ-DI) Response Week 48 (n=446)	76.5 percentage of participants	—	—
Percentage of Participants Achieving Clinical Meaningful Health Assessment Questionnaire Disability Index (HAQ-DI) Response Week 60 (n=327)	76.8 percentage of participants	—	—
Percentage of Participants Achieving Clinical Meaningful Health Assessment Questionnaire Disability Index (HAQ-DI) Response Week 72 (n=218)	77.5 percentage of participants	—	—
Percentage of Participants Achieving Clinical Meaningful Health Assessment Questionnaire Disability Index (HAQ-DI) Response Week 84 (n=119)	76.5 percentage of participants	—	—
Percentage of Participants Achieving Clinical Meaningful Health Assessment Questionnaire Disability Index (HAQ-DI) Response Week 96 (n=55)	89.1 percentage of participants	—	—
Percentage of Participants Achieving Clinical Meaningful Health Assessment Questionnaire Disability Index (HAQ-DI) Response Week 108 (n=42)	90.5 percentage of participants	—	—

SECONDARY outcome

Timeframe: Extension Weeks 12, 24, 36 ,48, 60, 72, 84, 96, 108

The Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis, consisting of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. There are 4 possible responses for each question: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty and 3=unable to do. The score for each of the domains is the highest (worst) score in each domain. A patient must have a domain score for at least 6 of 8 domains to calculate a valid HAQ-DI score which is the sum of domain scores, divided by the number of domains that have a score for a total possible score minimum/maximum 0 (best) to 3 (worst). Clinical Remission is defined as a HAQ-DI score \< 0.5.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Percentage of Participants Achieving Health Assessment Questionnaire Disability Index (HAQ-DI) Clinical Remission Week 12 (n=900)	32.1 percentage of participants	—	—
Percentage of Participants Achieving Health Assessment Questionnaire Disability Index (HAQ-DI) Clinical Remission Week 24 (n=770)	33.4 percentage of participants	—	—
Percentage of Participants Achieving Health Assessment Questionnaire Disability Index (HAQ-DI) Clinical Remission Week 36 (n=614)	34.5 percentage of participants	—	—
Percentage of Participants Achieving Health Assessment Questionnaire Disability Index (HAQ-DI) Clinical Remission Week 48 (n=446)	33.2 percentage of participants	—	—
Percentage of Participants Achieving Health Assessment Questionnaire Disability Index (HAQ-DI) Clinical Remission Week 60 (n=327)	37.0 percentage of participants	—	—
Percentage of Participants Achieving Health Assessment Questionnaire Disability Index (HAQ-DI) Clinical Remission Week 72 (n=218)	34.9 percentage of participants	—	—
Percentage of Participants Achieving Health Assessment Questionnaire Disability Index (HAQ-DI) Clinical Remission Week 84 (n=119)	38.7 percentage of participants	—	—
Percentage of Participants Achieving Health Assessment Questionnaire Disability Index (HAQ-DI) Clinical Remission Week 96 (n=55)	41.8 percentage of participants	—	—
Percentage of Participants Achieving Health Assessment Questionnaire Disability Index (HAQ-DI) Clinical Remission Week 108 (n=42)	50.0 percentage of participants	—	—

SECONDARY outcome

Timeframe: Core Baseline, Extension Weeks 12, 24, 36 ,48, 60, 72, 84, 96, 108

The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Change From Baseline in Quality of Life Short Form (SF-36): Physical Component Score Week 12 (n=885)	9.86 score on a scale Standard Deviation 10.548	—	—
Change From Baseline in Quality of Life Short Form (SF-36): Physical Component Score Week 24 (n=747)	9.30 score on a scale Standard Deviation 10.291	—	—
Change From Baseline in Quality of Life Short Form (SF-36): Physical Component Score Week 36 (n=607)	9.54 score on a scale Standard Deviation 10.580	—	—
Change From Baseline in Quality of Life Short Form (SF-36): Physical Component Score Week 48 (n=444)	9.82 score on a scale Standard Deviation 11.025	—	—
Change From Baseline in Quality of Life Short Form (SF-36): Physical Component Score Week 60 (n=324)	10.34 score on a scale Standard Deviation 10.837	—	—
Change From Baseline in Quality of Life Short Form (SF-36): Physical Component Score Week 72 (n=217)	10.38 score on a scale Standard Deviation 11.157	—	—
Change From Baseline in Quality of Life Short Form (SF-36): Physical Component Score Week 84 (n=117)	10.62 score on a scale Standard Deviation 10.378	—	—
Change From Baseline in Quality of Life Short Form (SF-36): Physical Component Score Week 96 (n=55)	13.06 score on a scale Standard Deviation 9.175	—	—
Change From Baseline in Quality of Life Short Form (SF-36): Physical Component Score Week 108 (n=42)	13.59 score on a scale Standard Deviation 9.932	—	—

SECONDARY outcome

Timeframe: Core Baseline, Extension Weeks 12, 24, 36 ,48, 60, 72, 84, 96, 108

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Change From Baseline in Quality of Life Short Form (SF-36):Mental Component Score Week 12 (n=885)	8.10 score on a scale Standard Deviation 14.426	—	—
Change From Baseline in Quality of Life Short Form (SF-36):Mental Component Score Week 24 (n=747)	8.37 score on a scale Standard Deviation 14.607	—	—
Change From Baseline in Quality of Life Short Form (SF-36):Mental Component Score Week 36 (n=607)	9.43 score on a scale Standard Deviation 14.311	—	—
Change From Baseline in Quality of Life Short Form (SF-36):Mental Component Score Week 48 (n=444)	8.27 score on a scale Standard Deviation 13.868	—	—
Change From Baseline in Quality of Life Short Form (SF-36):Mental Component Score Week 60 (n=324)	9.67 score on a scale Standard Deviation 13.91	—	—
Change From Baseline in Quality of Life Short Form (SF-36):Mental Component Score Week 72 (n=217)	8.30 score on a scale Standard Deviation 13.515	—	—
Change From Baseline in Quality of Life Short Form (SF-36):Mental Component Score Week 84 (n=117)	7.36 score on a scale Standard Deviation 14.466	—	—
Change From Baseline in Quality of Life Short Form (SF-36):Mental Component Score Week 96 (n=55)	10.57 score on a scale Standard Deviation 14.365	—	—
Change From Baseline in Quality of Life Short Form (SF-36):Mental Component Score Week 108 (n=42)	7.42 score on a scale Standard Deviation 12.272	—	—

SECONDARY outcome

Timeframe: Core Baseline, Extension Weeks 12, 24, 36 ,48, 60, 72, 84, 96, 108

FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status. A positive change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Tocilizumab Monotherapy n=934 Participants Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were not taking DMARDS at Core Baseline.	Tocilizumab + 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking one DMARD at Core study Baseline.	Tocilizumab + > 1 DMARD Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first, in a subset of patients who were taking more than one DMARD at Core study Baseline.
Change From Baseline in FACIT-Fatigue Score Week 12 (n=900)	10.67 score on a scale Standard Deviation 11.287	—	—
Change From Baseline in FACIT-Fatigue Score Week 24 (n=765)	10.70 score on a scale Standard Deviation 11.239	—	—
Change From Baseline in FACIT-Fatigue Score Week 36 (n=613)	11.42 score on a scale Standard Deviation 11.826	—	—
Change From Baseline in FACIT-Fatigue Score Week 48 (n=447)	11.02 score on a scale Standard Deviation 11.684	—	—
Change From Baseline in FACIT-Fatigue Score Week 60 (n=326)	11.77 score on a scale Standard Deviation 11.660	—	—
Change From Baseline in FACIT-Fatigue Score Week 72 (n=217)	10.71 score on a scale Standard Deviation 11.170	—	—
Change From Baseline in FACIT-Fatigue Score Week 84 (n=119)	10.63 score on a scale Standard Deviation 11.602	—	—
Change From Baseline in FACIT-Fatigue Score Week 96 (n=55)	11.69 score on a scale Standard Deviation 10.374	—	—
Change From Baseline in FACIT-Fatigue Score Week 108 (n=42)	10.56 score on a scale Standard Deviation 10.636	—	—

Adverse Events

Tocilizumab

Serious events: 60 serious events

Other events: 141 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tocilizumab n=934 participants at risk Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first.
Infections and infestations Cellulitis	0.54% 5/934 • 108 Weeks
Infections and infestations Pneumonia	0.54% 5/934 • 108 Weeks
Infections and infestations Diverticulitis	0.21% 2/934 • 108 Weeks
Infections and infestations Abscess limb	0.11% 1/934 • 108 Weeks
Infections and infestations Appendicitis	0.11% 1/934 • 108 Weeks
Infections and infestations Campylobacter gastroenteritis	0.11% 1/934 • 108 Weeks
Infections and infestations Epiglottitis	0.11% 1/934 • 108 Weeks
Infections and infestations Gastroenteritis	0.11% 1/934 • 108 Weeks
Infections and infestations Intervertebral discitis	0.11% 1/934 • 108 Weeks
Infections and infestations Periorbital cellulitis	0.11% 1/934 • 108 Weeks
Infections and infestations Postoperative wound infection	0.11% 1/934 • 108 Weeks
Infections and infestations Sepsis	0.11% 1/934 • 108 Weeks
Infections and infestations Staphylococcal infection	0.11% 1/934 • 108 Weeks
Nervous system disorders Cerebrovascular accident	0.21% 2/934 • 108 Weeks
Nervous system disorders Cerebral infarction	0.11% 1/934 • 108 Weeks
Nervous system disorders Cognitive Disorder	0.11% 1/934 • 108 Weeks
Nervous system disorders Demyelination	0.11% 1/934 • 108 Weeks
Nervous system disorders Epilepsy	0.11% 1/934 • 108 Weeks
Nervous system disorders Headache	0.11% 1/934 • 108 Weeks
Nervous system disorders Intracranial aneurysm	0.11% 1/934 • 108 Weeks
Nervous system disorders Syncope	0.11% 1/934 • 108 Weeks
Nervous system disorders Transient Ischaemic attack	0.11% 1/934 • 108 Weeks
Musculoskeletal and connective tissue disorders Osteoarthritis	0.21% 2/934 • 108 Weeks
Musculoskeletal and connective tissue disorders Arthropathy	0.11% 1/934 • 108 Weeks
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.11% 1/934 • 108 Weeks
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.11% 1/934 • 108 Weeks
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.11% 1/934 • 108 Weeks
Musculoskeletal and connective tissue disorders Synovitis	0.11% 1/934 • 108 Weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.11% 1/934 • 108 Weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.11% 1/934 • 108 Weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.11% 1/934 • 108 Weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma metastatic	0.11% 1/934 • 108 Weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pituitary tumour benign	0.11% 1/934 • 108 Weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal oncocytoma	0.11% 1/934 • 108 Weeks
Injury, poisoning and procedural complications Accidental Overdose	0.11% 1/934 • 108 Weeks
Injury, poisoning and procedural complications Femur fracture	0.11% 1/934 • 108 Weeks
Injury, poisoning and procedural complications Foreign body	0.11% 1/934 • 108 Weeks
Injury, poisoning and procedural complications Joint dislocation	0.11% 1/934 • 108 Weeks
Injury, poisoning and procedural complications Post procedural haemorrhage	0.11% 1/934 • 108 Weeks
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.11% 1/934 • 108 Weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.11% 1/934 • 108 Weeks
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.11% 1/934 • 108 Weeks
Respiratory, thoracic and mediastinal disorders Hydrothorax	0.11% 1/934 • 108 Weeks
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.11% 1/934 • 108 Weeks
Cardiac disorders Myocardial infarction	0.21% 2/934 • 108 Weeks
Cardiac disorders Atrial flutter	0.11% 1/934 • 108 Weeks
Cardiac disorders Cardiac arrest	0.11% 1/934 • 108 Weeks
General disorders Asthenia	0.11% 1/934 • 108 Weeks
General disorders Device breakage	0.11% 1/934 • 108 Weeks
General disorders Device dislocation	0.11% 1/934 • 108 Weeks
General disorders Non-cardiac chest pain	0.11% 1/934 • 108 Weeks
Gastrointestinal disorders Colitis ischaemic	0.11% 1/934 • 108 Weeks
Gastrointestinal disorders Large intestine perforation	0.11% 1/934 • 108 Weeks
Gastrointestinal disorders Pancreatitis acute	0.11% 1/934 • 108 Weeks
Hepatobiliary disorders Cholecystitis	0.11% 1/934 • 108 Weeks
Hepatobiliary disorders Cholelithiasis	0.11% 1/934 • 108 Weeks
Blood and lymphatic system disorders Thymus enlargement	0.11% 1/934 • 108 Weeks
Metabolism and nutrition disorders Dehydration	0.11% 1/934 • 108 Weeks
Pregnancy, puerperium and perinatal conditions Abortion missed	0.11% 1/934 • 108 Weeks
Surgical and medical procedures Central venous catheterisation	0.11% 1/934 • 108 Weeks

Other adverse events

Other adverse events
Measure	Tocilizumab n=934 participants at risk Participants received tocilizumab 8 mg/kg IV, maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first.
Infections and infestations Nasopharyngitis	9.5% 89/934 • 108 Weeks
Infections and infestations Upper respiratory tract infection	5.6% 52/934 • 108 Weeks

Additional Information

Medical Communications

Hoffman-LaRoche

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