Trial Outcomes & Findings for A Study Of Tocilizumab in Patients With Moderate to Severe Active Rheumatoid Arthritis Who Have an Inadequate Response to or Are Unable to Tolerate Biologic and Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) (NCT NCT00891020)

Last Updated: 2012-10-25

Results Overview

An SAE was any adverse event that at any dose fulfilled at least one of the following criteria: * Was fatal (results 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 * Was medically significant or required intervention to prevent one or other of the outcomes listed above.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

886 participants

Primary outcome timeframe

24 Weeks

Results posted on

2012-10-25

Participant Flow

1129 patients were screened for the study. Of these 1129 patients, 886 patients were enrolled and 243 patients were screen failures.

Participant milestones

Participant milestones
Measure	Tocilizumab 8 mg/kg Monotherapy Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 4 mg/kg + DMARD Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 8 mg/kg + DMARD Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.
24 Week Treatment Period STARTED	163	363	360
24 Week Treatment Period Intent-to-Treat (ITT)	163	362	358
24 Week Treatment Period Safety Set	138	364	381
24 Week Treatment Period COMPLETED	126	303	302
24 Week Treatment Period NOT COMPLETED	37	60	58
Long-term Extension Period STARTED	55	196	193
Long-term Extension Period COMPLETED	49	172	170
Long-term Extension Period NOT COMPLETED	6	24	23

Reasons for withdrawal

Reasons for withdrawal
Measure	Tocilizumab 8 mg/kg Monotherapy Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 4 mg/kg + DMARD Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 8 mg/kg + DMARD Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.
24 Week Treatment Period Adverse event or intercurrent illness	11	32	17
24 Week Treatment Period Death	0	2	0
24 Week Treatment Period Insufficient therapeutic response	6	9	15
24 Week Treatment Period Failure to return	4	5	5
24 Week Treatment Period Violation of selection criteria at entry	1	0	2
24 Week Treatment Period Other protocol violation	1	1	2
24 Week Treatment Period Refused treatment/did not cooperate	3	2	1
24 Week Treatment Period Withdrew consent	6	3	15
24 Week Treatment Period Administrative/Other	5	6	1
Long-term Extension Period Adverse Event	1	11	10
Long-term Extension Period Death	0	0	1
Long-term Extension Period Insufficient therapeutic response	3	2	2
Long-term Extension Period Protocol Violation	0	1	1
Long-term Extension Period Refused treatment/did not cooperate	1	6	4
Long-term Extension Period Failure to return	0	2	3
Long-term Extension Period Administrative	1	2	2

Baseline Characteristics

A Study Of Tocilizumab in Patients With Moderate to Severe Active Rheumatoid Arthritis Who Have an Inadequate Response to or Are Unable to Tolerate Biologic and Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tocilizumab 8 mg/kg Monotherapy n=138 Participants Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 4 mg/kg + DMARD n=364 Participants Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 8 mg/kg + DMARD n=381 Participants Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Total n=883 Participants Total of all reporting groups
Age Continuous	53.5 years STANDARD_DEVIATION 12.63 • n=5 Participants	55.6 years STANDARD_DEVIATION 11.92 • n=7 Participants	54.0 years STANDARD_DEVIATION 12.11 • n=5 Participants	54.6 years STANDARD_DEVIATION 12.13 • n=4 Participants
Sex: Female, Male Female	110 Participants n=5 Participants	273 Participants n=7 Participants	296 Participants n=5 Participants	679 Participants n=4 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	91 Participants n=7 Participants	85 Participants n=5 Participants	204 Participants n=4 Participants

PRIMARY outcome

Timeframe: 24 Weeks

Population: Safety Population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg Monotherapy n=138 Participants Participants received Tocilizumab (TCZ) 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 4 mg/kg + DMARD n=364 Participants Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 8 mg/kg + DMARD n=381 Participants Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.
Percentage of Participants Experiencing at Least One Serious Adverse Event (SAE) During the 24 Week Treatment Period	5.8 Percentage of Participants	8.0 Percentage of Participants	8.4 Percentage of Participants

SECONDARY outcome

Timeframe: 24 Weeks

Serious Adverse Events of Special interest include: * Serious infections including opportunistic infections * Complications of diverticulitis (including lower gastrointestinal \[GI\] perforations) * Myocardial infarction/acute coronary syndrome * Stroke * Spontaneous or serious bleeding * Malignant neoplasms

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg Monotherapy n=138 Participants Participants received Tocilizumab (TCZ) 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 4 mg/kg + DMARD n=364 Participants Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 8 mg/kg + DMARD n=381 Participants Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.
Percentage of Participants Experiencing Serious Adverse Events of Special Interest Serious Infections (including opportunistic)	2.9 Percentage of Participants	3.6 Percentage of Participants	3.9 Percentage of Participants
Percentage of Participants Experiencing Serious Adverse Events of Special Interest Gastrointestinal Perforations and Related Events	0 Percentage of Participants	0.8 Percentage of Participants	0 Percentage of Participants
Percentage of Participants Experiencing Serious Adverse Events of Special Interest Myocardial Infarction/Acute Coronary Syndrome	0 Percentage of Participants	0 Percentage of Participants	0.3 Percentage of Participants
Percentage of Participants Experiencing Serious Adverse Events of Special Interest Stroke	0 Percentage of Participants	0.3 Percentage of Participants	0 Percentage of Participants
Percentage of Participants Experiencing Serious Adverse Events of Special Interest Spontaneous/Serious Bleeding	0 Percentage of Participants	0.3 Percentage of Participants	0.3 Percentage of Participants
Percentage of Participants Experiencing Serious Adverse Events of Special Interest Malignant Neoplasms	0 Percentage of Participants	0 Percentage of Participants	0.3 Percentage of Participants

SECONDARY outcome

Timeframe: 24 Weeks

Non-serious adverse Events of Special interest include: * Serious/Medically Significant Hepatic Events * Spontaneous /Serious Bleeding * Malignant Neoplasms

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg Monotherapy n=138 Participants Participants received Tocilizumab (TCZ) 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 4 mg/kg + DMARD n=364 Participants Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 8 mg/kg + DMARD n=381 Participants Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.
Percentage of Participants Experiencing Non-serious Adverse Events of Special Interest Serious/Medically Significant Hepatic Events	0 Percentage of Participants	0 Percentage of Participants	0.3 Percentage of Participants
Percentage of Participants Experiencing Non-serious Adverse Events of Special Interest Spontaneous/Serious Bleeding	4.3 Percentage of Participants	3.3 Percentage of Participants	7.3 Percentage of Participants
Percentage of Participants Experiencing Non-serious Adverse Events of Special Interest Malignant Neoplasms	0 Percentage of Participants	0.3 Percentage of Participants	0.3 Percentage of Participants

SECONDARY outcome

Timeframe: Weeks 8,16,24

Population: Intent-to-treat population includes participants who received at least one dose of study drug. Patients were included in the treatment group to which they were randomized or assigned, regardless of the treatment actually received. "n" in each of the categories is the number of participants with data available for analysis at the given time point.

Clinical Remission is defined as a Disease Activity Score 28 \[DAS28\] \< 2.6. The DAS28 is a combined index for measuring disease activity in RA. The index includes tender joint count (TJC) -28 joints and swollen joint count (SJC)-28 joints, acute phase response (CRP) and general health status. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg Monotherapy n=163 Participants Participants received Tocilizumab (TCZ) 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 4 mg/kg + DMARD n=362 Participants Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 8 mg/kg + DMARD n=358 Participants Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.
Percentage of Participants Achieving Clinical Remission at Weeks 8, 16, and 24 Week 8 (n=147, 337, 334)	8.8 Percentage of Participants	6.8 Percentage of Participants	12.9 Percentage of Participants
Percentage of Participants Achieving Clinical Remission at Weeks 8, 16, and 24 Week 16 (n=127, 317, 304)	15.7 Percentage of Participants	17.4 Percentage of Participants	22.0 Percentage of Participants
Percentage of Participants Achieving Clinical Remission at Weeks 8, 16, and 24 Week 24 (n=126, 286, 302)	19.8 Percentage of Participants	20.6 Percentage of Participants	25.2 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 8,16,24

Population: Intent-to-treat includes participants who received at least one dose of study drug. Patients were included in the treatment group to which they were randomized or assigned, regardless of the treatment actually received. "n" in each of the categories is the number of participants with data available for analysis at the given time point.

The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes tender joint count (TJC) -28 joints and swollen joint count (SJC)-28 joints, acute phase response C-reactive protein (CRP) and general health status. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of \< 2.6 represents clinical remission, a score of ≤ 3.2 represents low disease activity, and a score of \> 5.1 represents high disease activity. The Change from Baseline to Weeks 8, 16 and 24 is reported.

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg Monotherapy n=163 Participants Participants received Tocilizumab (TCZ) 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 4 mg/kg + DMARD n=362 Participants Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 8 mg/kg + DMARD n=358 Participants Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.
Change From Baseline in DAS28 Score at Weeks 8, 16 and 24 Week 8 (n=147, 337, 334)	-1.75 Score on a scale Standard Deviation 1.213	-1.00 Score on a scale Standard Deviation 1.189	-1.54 Score on a scale Standard Deviation 1.187
Change From Baseline in DAS28 Score at Weeks 8, 16 and 24 Week 16 (n=127, 317, 304)	-2.07 Score on a scale Standard Deviation 1.406	-1.66 Score on a scale Standard Deviation 1.244	-1.87 Score on a scale Standard Deviation 1.322
Change From Baseline in DAS28 Score at Weeks 8, 16 and 24 Week 24 (n=126, 286, 302)	-2.03 Score on a scale Standard Deviation 1.384	-1.81 Score on a scale Standard Deviation 1.264	-1.94 Score on a scale Standard Deviation 1.380

SECONDARY outcome

Timeframe: Baseline, Weeks 8,16,24

Population: Intent-to-treat population includes all participants who received at least one dose of study drug. Patients were included in the treatment group to which they were randomized or assigned, regardless of the treatment actually received.

The ACR response rates ACR20, ACR50, and ACR70 are defined as ≥20%, ≥50%, and ≥70% improvement from baseline, respectively, in: 1. Swollen Joint Count (66 joints) and Tender Joint Count (68 joints) and 2. At least 3 of the following 5 assessments: * Patient's global assessment of pain-Visual Analog Scale (VAS) * Patient global assessment of disease activity-(VAS) * Physician global assessment of disease activity-(VAS) * Patient assessment of disability (physical function scale of the Multidimensional Health Assessment Questionnaire) * Acute phase response C-Reactive Protein (CRP)

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg Monotherapy n=163 Participants Participants received Tocilizumab (TCZ) 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 4 mg/kg + DMARD n=362 Participants Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 8 mg/kg + DMARD n=358 Participants Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.
Percentage of Participants Achieving American College of Rheumatology (ACR) (ACR20/50/70) Responses at Weeks 8, 16, and 24 Week 8 ACR20 responders	40.5 Percentage of Participants	37.8 Percentage of Participants	40.8 Percentage of Participants
Percentage of Participants Achieving American College of Rheumatology (ACR) (ACR20/50/70) Responses at Weeks 8, 16, and 24 Week 8 ACR50 responders	14.7 Percentage of Participants	11.9 Percentage of Participants	16.8 Percentage of Participants
Percentage of Participants Achieving American College of Rheumatology (ACR) (ACR20/50/70) Responses at Weeks 8, 16, and 24 Week 8 ACR70 responders	4.3 Percentage of Participants	3.3 Percentage of Participants	5.6 Percentage of Participants
Percentage of Participants Achieving American College of Rheumatology (ACR) (ACR20/50/70) Responses at Weeks 8, 16, and 24 Week 16 ACR20 responders	46.6 Percentage of Participants	43.9 Percentage of Participants	45.3 Percentage of Participants
Percentage of Participants Achieving American College of Rheumatology (ACR) (ACR20/50/70) Responses at Weeks 8, 16, and 24 Week 16 ACR50 responders	23.3 Percentage of Participants	19.9 Percentage of Participants	22.3 Percentage of Participants
Percentage of Participants Achieving American College of Rheumatology (ACR) (ACR20/50/70) Responses at Weeks 8, 16, and 24 Week 16 ACR70 responders	7.4 Percentage of Participants	8.6 Percentage of Participants	9.8 Percentage of Participants
Percentage of Participants Achieving American College of Rheumatology (ACR) (ACR20/50/70) Responses at Weeks 8, 16, and 24 Week 24 ACR20 responders	47.9 Percentage of Participants	44.8 Percentage of Participants	49.7 Percentage of Participants
Percentage of Participants Achieving American College of Rheumatology (ACR) (ACR20/50/70) Responses at Weeks 8, 16, and 24 Week 24 ACR50 responders	24.5 Percentage of Participants	24.3 Percentage of Participants	27.1 Percentage of Participants
Percentage of Participants Achieving American College of Rheumatology (ACR) (ACR20/50/70) Responses at Weeks 8, 16, and 24 Week 24 ACR70 responders	7.4 Percentage of Participants	8.8 Percentage of Participants	10.3 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Week 8

Dosage could be increased from 4 mg/kg Tocilizumab to 8 mg/kg due to failure to achieve 20% improvement from baseline in swollen and tender joint counts.

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg Monotherapy n=364 Participants Participants received Tocilizumab (TCZ) 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 4 mg/kg + DMARD Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 8 mg/kg + DMARD Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.
Percentage of Participants With Tocilizumab Dose Increased From 4 mg/kg to 8 mg/kg at Week 8	39.9 Percentage of Participants	—	—

SECONDARY outcome

Timeframe: Weeks 12,16, 20

Population: Safety population includes participants who received at least one dose of study drug. "n" in each of the categories is the number of participants previously on 4mg/kg + DMARD and receiving a dose at the current visit. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period.

Dosage of Tocilizumab 4 mg/kg could be increased to 8 mg/kg at the discretion of the investigator based on assessment of the patient's benefit-risk after Week 12.

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg Monotherapy n=364 Participants Participants received Tocilizumab (TCZ) 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 4 mg/kg + DMARD Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 8 mg/kg + DMARD Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.
Number of Participants Having Their Tocilizumab Dose Increased From 4 mg/kg to 8 mg/kg at Weeks 12, 16, and 20 Week 12 (n=183)	41 Participants	—	—
Number of Participants Having Their Tocilizumab Dose Increased From 4 mg/kg to 8 mg/kg at Weeks 12, 16, and 20 Week 16 (n=138)	18 Participants	—	—
Number of Participants Having Their Tocilizumab Dose Increased From 4 mg/kg to 8 mg/kg at Weeks 12, 16, and 20 Week 20 (n=119)	5 Participants	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 8,16,24

Population: Intent-to-treat population includes all participants who received at least 1 dose of study drug. Patients were included in the treatment group to which they were randomized or assigned, regardless of the treatment actually received. "n" in each of the categories is the number of participants with data available for analysis at the given time point.

The RAPID3 is a combined index derived from the Multidimensional Health Assessment Questionnaire that includes physical function score, pain Visual Analog Scale (VAS), and global assessment of disease activity VAS. The total RAPID3 score ranges from 0 to 10 where higher scores represent worse outcomes. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg Monotherapy n=163 Participants Participants received Tocilizumab (TCZ) 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 4 mg/kg + DMARD n=362 Participants Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 8 mg/kg + DMARD n=358 Participants Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.
Change From Baseline in Routine Assessment Patient Index Data (RAPID3) Score at Weeks 8, 16, and 24 Week 8 (n=156, 348, 343)	-1.60 Score on a scale Standard Deviation 1.803	-1.10 Score on a scale Standard Deviation 1.848	-1.28 Score on a scale Standard Deviation 1.733
Change From Baseline in Routine Assessment Patient Index Data (RAPID3) Score at Weeks 8, 16, and 24 Week 16 (n=138, 325, 315)	-1.97 Score on a scale Standard Deviation 2.068	-1.42 Score on a scale Standard Deviation 1.896	-1.46 Score on a scale Standard Deviation 1.897
Change From Baseline in Routine Assessment Patient Index Data (RAPID3) Score at Weeks 8, 16, and 24 Week 24 (n=134, 306, 308)	-1.83 Score on a scale Standard Deviation 1.978	-1.61 Score on a scale Standard Deviation 1.972	-1.46 Score on a scale Standard Deviation 1.962

SECONDARY outcome

Timeframe: Baseline, Weeks 8,16,24

The fatigue VAS is a single-item, patient-reported outcome that measures the severity of the fatigue over the past week. Patients rate their fatigue on a scale of 0 (fatigue is no problem) to 100 (fatigue is a major problem). Higher scores represent higher disease activity and a negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Tocilizumab 8 mg/kg Monotherapy n=163 Participants Participants received Tocilizumab (TCZ) 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 4 mg/kg + DMARD n=362 Participants Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 8 mg/kg + DMARD n=358 Participants Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.
Change From Baseline in Fatigue Visual Analogue Scale (VAS) at Weeks 8, 16, and 24 Week 8 (n=156, 350, 344)	-13.17 Score on a scale Standard Deviation 25.584	-10.06 Score on a scale Standard Deviation 25.349	-13.33 Score on a scale Standard Deviation 24.950
Change From Baseline in Fatigue Visual Analogue Scale (VAS) at Weeks 8, 16, and 24 Week 16 (n=138, 329, 317)	-19.38 Score on a scale Standard Deviation 26.639	-14.00 Score on a scale Standard Deviation 26.282	-15.58 Score on a scale Standard Deviation 25.802
Change From Baseline in Fatigue Visual Analogue Scale (VAS) at Weeks 8, 16, and 24 Week 24 (n=135, 307, 312)	-15.85 Score on a scale Standard Deviation 26.881	-16.73 Score on a scale Standard Deviation 26.261	-16.07 Score on a scale Standard Deviation 26.321

Adverse Events

Tocilizumab 8 mg/kg Monotherapy

Serious events: 11 serious events

Other events: 63 other events

Deaths: 0 deaths

Tocilizumab 4 mg/kg + DMARD

Serious events: 45 serious events

Other events: 185 other events

Deaths: 0 deaths

Tocilizumab 8 mg/kg + DMARD

Serious events: 40 serious events

Other events: 189 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Tocilizumab 8 mg/kg Monotherapy n=138 participants at risk Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 4 mg/kg + DMARD n=364 participants at risk Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.	Tocilizumab 8 mg/kg + DMARD n=381 participants at risk Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase.
Infections and infestations Upper respiratory tract infection	10.1% 14/138 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	9.9% 36/364 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	10.8% 41/381 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	8.7% 12/138 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	11.0% 40/364 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	8.4% 32/381 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.
Infections and infestations Sinusitis	8.0% 11/138 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	9.1% 33/364 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	9.4% 36/381 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.
Nervous system disorders Headache	5.1% 7/138 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	7.4% 27/364 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	6.8% 26/381 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.
Infections and infestations Nasopharyngitis	5.1% 7/138 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	8.5% 31/364 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	5.0% 19/381 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.
Gastrointestinal disorders Diarrhoea	6.5% 9/138 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	6.9% 25/364 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	3.7% 14/381 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.
Investigations Alanine aminotransferase increased	5.8% 8/138 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	3.6% 13/364 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	6.8% 26/381 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.
Skin and subcutaneous tissue disorders Rash	2.9% 4/138 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	3.6% 13/364 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	6.0% 23/381 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.
Infections and infestations Urinary tract infection	5.8% 8/138 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	2.2% 8/364 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	5.0% 19/381 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.
Musculoskeletal and connective tissue disorders Arthralgia	5.1% 7/138 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	5.5% 20/364 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	5.8% 22/381 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.
Gastrointestinal disorders Nausea	3.6% 5/138 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	6.9% 25/364 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	4.2% 16/381 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.
General disorders Chest pain	5.1% 7/138 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	1.1% 4/364 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.	0.26% 1/381 • Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.

Additional Information

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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.
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Restriction type: OTHER