Trial Outcomes & Findings for A Study of RoActemra/Actemra and, if Initially Inadequately Responded to RoActemra/Actemra, Followed by MabThera/Rituxan in Patients With Rheumatoid Arthritis (NCT NCT01332994)

Last Updated: 2015-09-07

Results Overview

The DAS28 was calculated as \[0.28 times (x) the square root of number of swollen joints\] plus (+) \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of erythrocyte sedimentation rate (ESR)\] + \[0.014 x Visual Analog Scale (VAS) patient global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score \<2.6 at the assessment visit.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

519 participants

Primary outcome timeframe

Week 16

Results posted on

2015-09-07

Participant Flow

After a screening period of up to 4 weeks, eligible participants were treated according to a predefined treatment algorithm based on disease response. In certain cases a re-screening was allowed. Participants were enrolled into the study with the administration of their first dose.

Participant milestones

Participant milestones
Measure	Tocilizumab (TCZ)/TCZ or TCZ/Rituximab (RTX) All participants were assigned to receive TCZ 8 milligrams per kilogram (mg/kg) via intravenous (IV) infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using Disease Activity Score Based on 28-Joint Count (DAS28) to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of less than (\<) 2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score greater than (\>) 1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score less than or equal to (≤) 1.2 or a score \>3.2, received RTX 1000 milligrams (mg) via IV infusion at Weeks 16 and 18.
Overall Study STARTED	519
Overall Study Completed Week 16	463
Overall Study Completed Week 32 (TCZ/TCZ)	200
Overall Study Completed Week 32 (TCZ/RTX)	26
Overall Study Completed Week 66 (TCZ/RTX)	25
Overall Study COMPLETED	448
Overall Study NOT COMPLETED	71

Reasons for withdrawal

Reasons for withdrawal
Measure	Tocilizumab (TCZ)/TCZ or TCZ/Rituximab (RTX) All participants were assigned to receive TCZ 8 milligrams per kilogram (mg/kg) via intravenous (IV) infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using Disease Activity Score Based on 28-Joint Count (DAS28) to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of less than (\<) 2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score greater than (\>) 1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score less than or equal to (≤) 1.2 or a score \>3.2, received RTX 1000 milligrams (mg) via IV infusion at Weeks 16 and 18.
Overall Study Adverse Event	34
Overall Study Death	1
Overall Study Lack of Efficacy	1
Overall Study Lost to Follow-up	4
Overall Study Protocol Violation	6
Overall Study Withdrawal by Subject	15
Overall Study Administrative Problem	2
Overall Study Other	8

Baseline Characteristics

A Study of RoActemra/Actemra and, if Initially Inadequately Responded to RoActemra/Actemra, Followed by MabThera/Rituxan in Patients With Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TCZ/TCZ or TCZ/RTX n=519 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Age, Continuous	55.7 years STANDARD_DEVIATION 11.9 • n=5 Participants
Sex: Female, Male Female	352 Participants n=5 Participants
Sex: Female, Male Male	167 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 16

Population: Main ITT Population

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=519 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of Participants Achieving Remission at Week 16 According to DAS28	42.8 percentage of participants Interval 38.5 to 47.2

SECONDARY outcome

Timeframe: Weeks 4, 8, and 12

Population: Main ITT Population

The DAS28 was calculated as \[0.28 x the square root of number of swollen joints\] + \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of ESR\] + \[0.014 x VAS patient global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score \<2.6 at the assessment visit.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=519 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of Participants Achieving Remission According to DAS28 at Weeks 4, 8, and 12 Week 4	21.6 percentage of participants Interval 18.1 to 25.4
Percentage of Participants Achieving Remission According to DAS28 at Weeks 4, 8, and 12 Week 8	40.1 percentage of participants Interval 35.8 to 44.4
Percentage of Participants Achieving Remission According to DAS28 at Weeks 4, 8, and 12 Week 12	43.2 percentage of participants Interval 38.9 to 47.5

SECONDARY outcome

Timeframe: Weeks 16, 20, 24, and 28

Population: ITT2 Population: All participants who received at least one dose of TCZ in the first treatment period with at least one efficacy measurement under TCZ, receiving TCZ in the second treatment period.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=213 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of Participants Achieving Remission According to DAS28 at Weeks 16, 20, 24, and 28 Among Participants Treated With 8 Courses of Tocilizumab Week 16	1.4 percentage of participants Interval 0.3 to 4.1
Percentage of Participants Achieving Remission According to DAS28 at Weeks 16, 20, 24, and 28 Among Participants Treated With 8 Courses of Tocilizumab Week 20	41.3 percentage of participants Interval 34.6 to 48.2
Percentage of Participants Achieving Remission According to DAS28 at Weeks 16, 20, 24, and 28 Among Participants Treated With 8 Courses of Tocilizumab Week 24	51.2 percentage of participants Interval 44.3 to 58.1
Percentage of Participants Achieving Remission According to DAS28 at Weeks 16, 20, 24, and 28 Among Participants Treated With 8 Courses of Tocilizumab Week 28	55.9 percentage of participants Interval 48.9 to 62.6

SECONDARY outcome

Timeframe: Week 32

Population: ITT2 Population

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=213 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of Participants Achieving Remission According to DAS28 at Week 32 Among Participants Treated With 8 Courses of Tocilizumab	54.9 percentage of participants Interval 48.0 to 61.7

SECONDARY outcome

Timeframe: Week 32

Population: ITT3 Population

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=27 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of Participants Achieving Remission According to DAS28 at Week 32 Among Nonresponding Participants Treated With Rituximab	14.8 percentage of participants Interval 4.2 to 33.7

SECONDARY outcome

Timeframe: Week 16

Population: Main ITT Population

The DAS28 was calculated as \[0.28 x the square root of number of swollen joints\] + \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of ESR\] + \[0.014 x the patient global assessment of disease activity using a VAS\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. LDAS was defined as a DAS28 score \<3.2 at the assessment visit.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=519 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of Participants Achieving Low Disease Activity Score (LDAS) According to DAS28	68.8 percentage of participants Interval 64.6 to 72.8

SECONDARY outcome

Timeframe: Week 32

Population: ITT3 Population

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=27 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of Participants Achieving LDAS According to DAS28 Among Among Nonresponding Participants Treated With Rituximab	33.3 percentage of participants Interval 16.5 to 54.0

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Main ITT Population

The DAS28 was calculated as \[0.28 x the square root of number of swollen joints\] + \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of ESR\] + \[0.014 x VAS patient global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Reductions \>1.2 points from Baseline to the assessment visit were considered clinically relevant.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=519 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of Participants Achieving a Clinically Relevant Reduction From Baseline in DAS28 at Week 16	86.1 percentage of participants Interval 82.9 to 89.0

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, and 12

Population: Main ITT Population

The DAS28 was calculated as \[0.28 x the square root of number of swollen joints\] + \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of ESR\] + \[0.014 x VAS patient global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Reductions \>1.2 points from Baseline to the assessment visit were considered clinically relevant.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=519 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of Participants Achieving a Clinically Relevant Reduction From Baseline in DAS28 at Weeks 4, 8, and 12 Week 4	74.6 percentage of participants Interval 70.6 to 78.3
Percentage of Participants Achieving a Clinically Relevant Reduction From Baseline in DAS28 at Weeks 4, 8, and 12 Week 8	81.5 percentage of participants Interval 77.9 to 84.8
Percentage of Participants Achieving a Clinically Relevant Reduction From Baseline in DAS28 at Weeks 4, 8, and 12 Week 12	83.4 percentage of participants Interval 79.9 to 86.5

SECONDARY outcome

Timeframe: Weeks 16 and 32

Population: ITT3 Population: All participants who received at least one dose of TCZ in the first treatment period and at least one dose of RTX in the second treatment period with at least one efficacy measurement under RTX.

The DAS28 was calculated as \[0.28 x the square root of number of swollen joints\] + \[0.56 x the square root of number of tender joints\] + \[0.7 x the natural log of ESR\] + \[0.014 x VAS patient global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Reductions \>1.2 points from the reference visit (Week 16) to the assessment visit were considered clinically relevant.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=27 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of Participants Achieving a Clinically Relevant Reduction in DAS28 From Week 16 to Week 32 Among Nonresponding Participants Treated With Rituximab	37.0 percentage of participants Interval 19.4 to 57.6

SECONDARY outcome

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

Population: Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=516 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
DAS28 Scores During and After Treatment Baseline (n=516)	5.7 units on a scale Standard Deviation 1.0
DAS28 Scores During and After Treatment Week 4 (n=508)	3.6 units on a scale Standard Deviation 1.3
DAS28 Scores During and After Treatment Week 8 (n=491)	3.0 units on a scale Standard Deviation 1.4
DAS28 Scores During and After Treatment Week 12 (n=483)	2.8 units on a scale Standard Deviation 1.4
DAS28 Scores During and After Treatment Week 16 (n=485)	2.6 units on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, and 32

Population: ITT2 Population. Participants with evaluable data at the designated visit (number shown = n) were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=213 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
DAS28 Scores During and After Treatment Among Participants Treated With 8 Courses of Tocilizumab Baseline (n=213)	6.0 units on a scale Standard Deviation 0.9
DAS28 Scores During and After Treatment Among Participants Treated With 8 Courses of Tocilizumab Week 4 (n=213)	4.0 units on a scale Standard Deviation 1.2
DAS28 Scores During and After Treatment Among Participants Treated With 8 Courses of Tocilizumab Week 8 (n=205)	3.4 units on a scale Standard Deviation 1.2
DAS28 Scores During and After Treatment Among Participants Treated With 8 Courses of Tocilizumab Week 12 (n=207)	3.3 units on a scale Standard Deviation 1.1
DAS28 Scores During and After Treatment Among Participants Treated With 8 Courses of Tocilizumab Week 16 (n=213)	3.3 units on a scale Standard Deviation 0.6
DAS28 Scores During and After Treatment Among Participants Treated With 8 Courses of Tocilizumab Week 20 (n=206)	2.8 units on a scale Standard Deviation 1.0
DAS28 Scores During and After Treatment Among Participants Treated With 8 Courses of Tocilizumab Week 24 (n=197)	2.6 units on a scale Standard Deviation 1.1
DAS28 Scores During and After Treatment Among Participants Treated With 8 Courses of Tocilizumab Week 28 (n=200)	2.4 units on a scale Standard Deviation 1.1
DAS28 Scores During and After Treatment Among Participants Treated With 8 Courses of Tocilizumab Week 32 (n=193)	2.5 units on a scale Standard Deviation 1.2

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 24, and 32

Population: ITT3 Population. Participants with evaluable data at the designated visit (number shown = n) were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=27 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
DAS28 Scores During and After Treatment Among Nonresponding Participants Treated With Rituximab Baseline (n=27)	5.7 units on a scale Standard Deviation 1.0
DAS28 Scores During and After Treatment Among Nonresponding Participants Treated With Rituximab Week 4 (n=27)	4.5 units on a scale Standard Deviation 1.2
DAS28 Scores During and After Treatment Among Nonresponding Participants Treated With Rituximab Week 8 (n=26)	4.2 units on a scale Standard Deviation 1.5
DAS28 Scores During and After Treatment Among Nonresponding Participants Treated With Rituximab Week 12 (n=27)	4.8 units on a scale Standard Deviation 1.6
DAS28 Scores During and After Treatment Among Nonresponding Participants Treated With Rituximab Week 16 (n=27)	5.1 units on a scale Standard Deviation 1.2
DAS28 Scores During and After Treatment Among Nonresponding Participants Treated With Rituximab Week 24 (n=26)	4.6 units on a scale Standard Deviation 1.4
DAS28 Scores During and After Treatment Among Nonresponding Participants Treated With Rituximab Week 32 (n=26)	4.0 units on a scale Standard Deviation 1.5

SECONDARY outcome

Timeframe: Weeks 40, 48, 56, and 66

Population: ITT3 Population. Participants with evaluable data at the designated visit (number shown = n) were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=26 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
DAS28 Scores During Safety Follow-Up Among Nonresponding Participants Treated With Rituximab Week 40 (n=26)	3.9 units on a scale Standard Deviation 1.5
DAS28 Scores During Safety Follow-Up Among Nonresponding Participants Treated With Rituximab Week 48 (n=25)	3.9 units on a scale Standard Deviation 1.2
DAS28 Scores During Safety Follow-Up Among Nonresponding Participants Treated With Rituximab Week 56 (n=22)	4.1 units on a scale Standard Deviation 1.8
DAS28 Scores During Safety Follow-Up Among Nonresponding Participants Treated With Rituximab Week 66 (n=25)	3.9 units on a scale Standard Deviation 1.5

SECONDARY outcome

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

Population: Main ITT Population

Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from Baseline. Participants with a score ≤3.2 and reduction of \>1.2 points were assessed as having a 'good' response. Participants with a score \>3.2 with reduction of \>1.2 points, or a score ≤5.1 with reduction of \>0.6 to ≤1.2 points, were assessed as having a 'moderate' response. Participants with a score \>5.1 with reduction of \>0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as nonresponders with response recorded as 'none.'

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=519 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16 Week 16, Moderate	20.2 percentage of participants Interval 16.9 to 23.9
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16 Week 4, Good	36.0 percentage of participants Interval 31.9 to 40.3
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16 Week 4, Moderate	47.8 percentage of participants Interval 43.4 to 52.2
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16 Week 4, None	16.2 percentage of participants Interval 13.1 to 19.6
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16 Week 8, Good	56.1 percentage of participants Interval 51.7 to 60.4
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16 Week 8, Moderate	30.6 percentage of participants Interval 26.7 to 34.8
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16 Week 8, None	13.3 percentage of participants Interval 10.5 to 16.5
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16 Week 12, Good	61.1 percentage of participants Interval 56.7 to 65.3
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16 Week 12, Moderate	25.6 percentage of participants Interval 21.9 to 29.6
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16 Week 12, None	13.3 percentage of participants Interval 10.5 to 16.5
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16 Week 16, Good	68.2 percentage of participants Interval 64.0 to 72.2
Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16 Week 16, None	11.6 percentage of participants Interval 8.9 to 14.6

SECONDARY outcome

Timeframe: Weeks 16 and 32

Population: ITT3 Population

Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference visit (Week 16). Participants with a score ≤3.2 and reduction of \>1.2 points were assessed as having a 'good' response. Participants with a score \>3.2 with reduction of \>1.2 points, or a score ≤5.1 with reduction of \>0.6 to ≤1.2 points, were assessed as having a 'moderate' response. Participants with a score \>5.1 with reduction of \>0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as nonresponders with response recorded as 'none.'

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=27 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of Participants Achieving a Response According to EULAR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab Good	25.9 percentage of participants Interval 11.1 to 46.3
Percentage of Participants Achieving a Response According to EULAR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab Moderate	29.6 percentage of participants Interval 13.8 to 50.2
Percentage of Participants Achieving a Response According to EULAR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab None	44.4 percentage of participants Interval 25.5 to 64.7

SECONDARY outcome

Timeframe: Baseline and Weeks 20, 24, 28, and 32

Population: ITT2 Population

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=213 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 28, None	8.0 percentage of participants Interval 4.7 to 12.5
Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 20, Good	65.3 percentage of participants Interval 58.5 to 71.6
Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 20, Moderate	30.0 percentage of participants Interval 24.0 to 36.7
Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 20, None	4.7 percentage of participants Interval 2.3 to 8.5
Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24, Good	68.1 percentage of participants Interval 61.4 to 74.3
Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24, Moderate	23.9 percentage of participants Interval 18.4 to 30.3
Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24, None	8.0 percentage of participants Interval 4.7 to 12.5
Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 28, Good	72.8 percentage of participants Interval 66.3 to 78.6
Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 28, Moderate	19.2 percentage of participants Interval 14.2 to 25.2
Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32, Good	66.7 percentage of participants Interval 59.9 to 73.0
Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32, Moderate	20.7 percentage of participants Interval 15.4 to 26.7
Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32, None	12.7 percentage of participants Interval 8.5 to 17.9

SECONDARY outcome

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

Population: Main ITT Population

Response was determined using ACR criteria based upon assessment of 66 joints for swelling and 68 joints for tenderness; joints were classified dichotomously as swollen or not swollen and tender or not tender. Respectively, these assessments were used to generate a swollen joint count (SJC) ranging from 0 to 66 swollen joints and a tender joint count (TJC) ranging from 0 to 68 tender joints. Response was defined as a reduction from Baseline of at least 20% for one of the following: VAS scores for patient-reported pain, patient global assessment of disease activity, or physician global assessment of disease activity, Health Assessment Questionnaire Disability Index (HAQ-DI), or C-reactive protein (CRP); plus a reduction in individual SJC and TJC of 20% (ACR20), 50% (ACR50), or 70% (ACR70). VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.'

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=519 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16 Week 4, ACR20	39.1 percentage of participants Interval 34.9 to 43.5
Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16 Week 4, ACR50	15.0 percentage of participants Interval 12.1 to 18.4
Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16 Week 4, ACR70	5.8 percentage of participants Interval 3.9 to 8.1
Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16 Week 8, ACR20	61.1 percentage of participants Interval 56.7 to 65.3
Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16 Week 8, ACR50	33.5 percentage of participants Interval 29.5 to 37.8
Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16 Week 8, ACR70	15.2 percentage of participants Interval 12.2 to 18.6
Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16 Week 12, ACR20	64.0 percentage of participants Interval 59.7 to 68.1
Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16 Week 12, ACR50	42.8 percentage of participants Interval 38.5 to 47.2
Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16 Week 12, ACR70	20.2 percentage of participants Interval 16.9 to 23.9
Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16 Week 16, ACR20	67.1 percentage of participants Interval 62.8 to 71.1
Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16 Week 16, ACR50	45.7 percentage of participants Interval 41.3 to 50.1
Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16 Week 16, ACR70	24.5 percentage of participants Interval 20.8 to 28.4

SECONDARY outcome

Timeframe: Weeks 16 and 32

Population: ITT3 Population

Response was determined using ACR criteria based upon assessment of 66 joints for swelling and 68 joints for tenderness; joints were classified dichotomously as swollen or not swollen and tender or not tender. Respectively, these assessments were used to generate an SJC ranging from 0 to 66 swollen joints and a TJC ranging from 0 to 68 tender joints. Response was defined as a reduction from the reference visit (Week 16) of at least 20% for one of the following: VAS scores for patient-reported pain, patient global assessment of disease activity, or physician global assessment of disease activity, HAQ-DI, or CRP; plus a reduction in individual SJC and TJC of 20% (ACR20), 50% (ACR50), or 70% (ACR70). VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.'

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=27 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of Participants Achieving a Response According to ACR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab ACR20	40.7 percentage of participants Interval 22.4 to 61.2
Percentage of Participants Achieving a Response According to ACR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab ACR50	33.3 percentage of participants Interval 16.5 to 54.0
Percentage of Participants Achieving a Response According to ACR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab ACR70	22.2 percentage of participants Interval 8.6 to 42.3

SECONDARY outcome

Timeframe: Baseline and Weeks 20, 24, 28, and 32

Population: ITT2 Population

Response was determined using ACR criteria based upon assessment of 66 joints for swelling and 68 joints for tenderness; joints were classified dichotomously as swollen or not swollen and tender or not tender. Respectively, these assessments were used to generate an SJC ranging from 0 to 66 swollen joints and a TJC ranging from 0 to 68 tender joints. Response was defined as a reduction from Baseline of at least 20% for one of the following: VAS scores for patient-reported pain, patient global assessment of disease activity, or physician global assessment of disease activity, HAQ-DI, or CRP; plus a reduction in individual SJC and TJC of 20% (ACR20), 50% (ACR50), or 70% (ACR70). VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.'

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=213 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 20, ACR20	74.2 percentage of participants Interval 67.8 to 79.9
Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 20, ACR50	45.1 percentage of participants Interval 38.3 to 52.0
Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 20, ACR70	21.1 percentage of participants Interval 15.8 to 27.2
Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24, ACR20	72.8 percentage of participants Interval 66.3 to 78.6
Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24, ACR50	49.8 percentage of participants Interval 42.9 to 56.7
Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24, ACR70	21.6 percentage of participants Interval 16.3 to 27.7
Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 28, ACR20	73.2 percentage of participants Interval 66.8 to 79.1
Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 28, ACR50	53.1 percentage of participants Interval 46.1 to 59.9
Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 28, ACR70	30.5 percentage of participants Interval 24.4 to 37.2
Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32, ACR20	75.6 percentage of participants Interval 69.2 to 81.2
Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32, ACR50	54.9 percentage of participants Interval 48.0 to 61.7
Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32, ACR70	34.3 percentage of participants Interval 27.9 to 41.1

SECONDARY outcome

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

Population: Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included.

The CDAI was calculated as \[SJC + TJC + VAS patient global assessment of disease activity + VAS physician global assessment of disease activity\]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. The SDAI was determined by adding CRP level to the CDAI score. Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A reduction in either score at the assessment visit reflects improvement in disease.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=509 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change From Baseline in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) Scores at Weeks 4, 8, 12, and 16 CDAI, Week 4 (n=509)	-10.9 units on a scale Standard Deviation 10.2
Change From Baseline in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) Scores at Weeks 4, 8, 12, and 16 CDAI, Week 8 (n=497)	-16.5 units on a scale Standard Deviation 11.1
Change From Baseline in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) Scores at Weeks 4, 8, 12, and 16 CDAI, Week 12 (n=486)	-18.3 units on a scale Standard Deviation 11.5
Change From Baseline in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) Scores at Weeks 4, 8, 12, and 16 CDAI, Week 16 (n=485)	-19.4 units on a scale Standard Deviation 11.5
Change From Baseline in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) Scores at Weeks 4, 8, 12, and 16 SDAI, Week 4 (n=496)	-12.3 units on a scale Standard Deviation 10.6
Change From Baseline in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) Scores at Weeks 4, 8, 12, and 16 SDAI, Week 8 (n=489)	-17.9 units on a scale Standard Deviation 11.5
Change From Baseline in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) Scores at Weeks 4, 8, 12, and 16 SDAI, Week 12 (n=474)	-19.7 units on a scale Standard Deviation 11.9
Change From Baseline in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) Scores at Weeks 4, 8, 12, and 16 SDAI, Week 16 (n=471)	-20.7 units on a scale Standard Deviation 12.2

SECONDARY outcome

Timeframe: Weeks 16 and 32

Population: ITT3 Population. Participants with evaluable data at the designated visit (number shown = n) were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=25 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change From Week 16 to 32 in CDAI and SDAI Scores Among Nonresponding Participants Treated With Rituximab CDAI (n=25)	-14.2 units on a scale Standard Deviation 12.0
Change From Week 16 to 32 in CDAI and SDAI Scores Among Nonresponding Participants Treated With Rituximab SDAI (n=24)	-14.0 units on a scale Standard Deviation 12.5

SECONDARY outcome

Timeframe: Baseline and Weeks 20, 24, 28, and 32

Population: ITT2 Population. Participants with evaluable data at the designated visit (number shown = n) were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=208 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change From Baseline in CDAI and SDAI Scores at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab CDAI, Week 20 (n=208)	-21.7 units on a scale Standard Deviation 11.7
Change From Baseline in CDAI and SDAI Scores at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab CDAI, Week 24 (n=199)	-22.8 units on a scale Standard Deviation 11.4
Change From Baseline in CDAI and SDAI Scores at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab CDAI, Week 28 (n=200)	-24.6 units on a scale Standard Deviation 12.5
Change From Baseline in CDAI and SDAI Scores at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab CDAI, Week 32 (n=194)	-24.0 units on a scale Standard Deviation 13.4
Change From Baseline in CDAI and SDAI Scores at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab SDAI, Week 20 (n=200)	-22.9 units on a scale Standard Deviation 12.5
Change From Baseline in CDAI and SDAI Scores at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab SDAI, Week 24 (n=190)	-24.3 units on a scale Standard Deviation 12.1
Change From Baseline in CDAI and SDAI Scores at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab SDAI, Week 28 (n=195)	-25.9 units on a scale Standard Deviation 13.2
Change From Baseline in CDAI and SDAI Scores at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab SDAI, Week 32 (n=189)	-25.2 units on a scale Standard Deviation 14.0

SECONDARY outcome

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

Population: Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included.

Blood samples for laboratory assessments, including hemoglobin level, were collected prior to each dose of study medication. The mean hemoglobin level was determined at Baseline and for assessment visits by averaging the observed hemoglobin level among all participants providing evaluable blood samples. Change from Baseline was calculated as \[mean hemoglobin at the assessment visit minus mean hemoglobin at Baseline\] and expressed in grams per liter (g/L).

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=509 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change From Baseline in Hemoglobin at Weeks 4, 8, 12, and 16 Week 4 (n=509)	4.9 g/L Standard Deviation 7.2
Change From Baseline in Hemoglobin at Weeks 4, 8, 12, and 16 Week 8 (n=496)	6.4 g/L Standard Deviation 8.8
Change From Baseline in Hemoglobin at Weeks 4, 8, 12, and 16 Week 12 (n=483)	6.9 g/L Standard Deviation 9.1
Change From Baseline in Hemoglobin at Weeks 4, 8, 12, and 16 Week 16 (n=477)	7.5 g/L Standard Deviation 9.1

SECONDARY outcome

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

Population: Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included.

Blood samples for laboratory assessments, including CRP level, were collected prior to each dose of study medication. The mean CRP level was determined at Baseline and for assessment visits by averaging the observed CRP level among all participants providing evaluable blood samples. Change from Baseline was calculated as \[mean CRP at the assessment visit minus mean CRP at Baseline\] and expressed in milligrams per deciliter (mg/dL).

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=497 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change From Baseline in CRP at Weeks 4, 8, 12, and 16 Week 4 (n=497)	-1.4 mg/dL Standard Deviation 1.9
Change From Baseline in CRP at Weeks 4, 8, 12, and 16 Week 8 (n=492)	-1.4 mg/dL Standard Deviation 1.9
Change From Baseline in CRP at Weeks 4, 8, 12, and 16 Week 12 (n=476)	-1.4 mg/dL Standard Deviation 1.9
Change From Baseline in CRP at Weeks 4, 8, 12, and 16 Week 16 (n=471)	-1.3 mg/dL Standard Deviation 1.9

SECONDARY outcome

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

Population: Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included.

Blood samples for laboratory assessments, including ESR, were collected prior to each dose of study medication. The mean ESR was determined at Baseline and for assessment visits by averaging the observed ESR among all participants providing evaluable blood samples. Change from Baseline was calculated as \[mean ESR at the assessment visit minus mean ESR at Baseline\] and expressed in millimeters per hour (mm/h).

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=507 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change From Baseline in ESR at Weeks 4, 8, 12, and 16 Week 4 (n=507)	-25.2 mm/h Standard Deviation 18.1
Change From Baseline in ESR at Weeks 4, 8, 12, and 16 Week 8 (n=494)	-26.6 mm/h Standard Deviation 18.9
Change From Baseline in ESR at Weeks 4, 8, 12, and 16 Week 12 (n=484)	-26.3 mm/h Standard Deviation 19.1
Change From Baseline in ESR at Weeks 4, 8, 12, and 16 Week 16 (n=484)	-27.5 mm/h Standard Deviation 18.7

SECONDARY outcome

Timeframe: Weeks 16 and 32

Population: ITT3 Population. Participants with evaluable data at the designated visit were included.

Blood samples for laboratory assessments, including hemoglobin level, were collected prior to each dose of study medication. The mean hemoglobin level was determined at Baseline and for assessment visits by averaging the observed hemoglobin level among all participants providing evaluable blood samples. Change was calculated as \[mean hemoglobin at Week 32 minus mean hemoglobin at Week 16\] and expressed in g/L.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=26 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change in Hemoglobin From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab	-2.0 g/L Standard Deviation 8.3

SECONDARY outcome

Timeframe: Weeks 16 and 32

Population: ITT3 Population. Participants with evaluable data at the designated visit were included.

Blood samples for laboratory assessments, including CRP level, were collected prior to each dose of study medication. The mean CRP level was determined at Baseline and for assessment visits by averaging the observed CRP level among all participants providing evaluable blood samples. Change was calculated as \[mean CRP at Week 32 minus mean CRP at Week 16\] and expressed in mg/dL.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=25 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change in CRP From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab	0.7 mg/dL Standard Deviation 1.7

SECONDARY outcome

Timeframe: Weeks 16 and 32

Population: ITT3 Population. Participants with evaluable data at the designated visit were included.

Blood samples for laboratory assessments, including ESR, were collected prior to each dose of study medication. The mean ESR was determined at Baseline and for assessment visits by averaging the observed ESR among all participants providing evaluable blood samples. Change was calculated as \[mean ESR at Week 32 minus mean ESR at Week 16\] and expressed in mm/h.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=26 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change in ESR From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab	11.5 mm/h Standard Deviation 17.9

SECONDARY outcome

Timeframe: Baseline and Weeks 20, 24, 28, and 32

Population: ITT2 Population. Participants with evaluable data at the designated visit (number shown = n) were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=207 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change From Baseline in Hemoglobin at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24 (n=198)	6.6 g/L Standard Deviation 9.4
Change From Baseline in Hemoglobin at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 28 (n=197)	6.9 g/L Standard Deviation 9.5
Change From Baseline in Hemoglobin at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32 (n=197)	8.3 g/L Standard Deviation 10.4
Change From Baseline in Hemoglobin at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 20 (n=207)	5.5 g/L Standard Deviation 9.0

SECONDARY outcome

Timeframe: Baseline and Weeks 20, 24, 28, and 32

Population: ITT2 Population. Participants with evaluable data at the designated visit (number shown = n) were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=200 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change From Baseline in CRP at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 20 (n=200)	-1.3 mg/dL Standard Deviation 1.9
Change From Baseline in CRP at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24 (n=191)	-1.4 mg/dL Standard Deviation 1.9
Change From Baseline in CRP at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 28 (n=195)	-1.3 mg/dL Standard Deviation 1.9
Change From Baseline in CRP at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32 (n=192)	-1.3 mg/dL Standard Deviation 1.9

SECONDARY outcome

Timeframe: Baseline and Weeks 20, 24, 28, and 32

Population: ITT2 Population. Participants with evaluable data at the designated visit (number shown = n) were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=206 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change From Baseline in ESR at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 20 (n=206)	-28.6 mm/h Standard Deviation 17.6
Change From Baseline in ESR at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24 (n=197)	-29.4 mm/h Standard Deviation 18.0
Change From Baseline in ESR at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 28 (n=200)	-29.4 mm/h Standard Deviation 18.1
Change From Baseline in ESR at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32 (n=196)	-28.6 mm/h Standard Deviation 20.2

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Main ITT Population. Participants who withdrew for reasons other than insufficient therapeutic response were not included in the analysis.

Study discontinuation was documented by reason for each participant prematurely withdrawing from the study. The percentage of participants was calculated as the number withdrawing for insufficient therapeutic response divided by the total number of participants who began treatment.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=485 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of Participants Withdrawing From the Study for Insufficient Therapeutic Response	0.2 percentage of participants Interval 0.0 to 1.1

SECONDARY outcome

Timeframe: Baseline

Population: ITT1 Population: All participants who received at least one dose of TCZ in the first treatment period and who completed the study reaching remission at Week 16. Participants with evaluable data at the designated visit (number shown = n) were included.

Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional (cluster of differentiation \[CD\] 19-positive, immunoglobulin (Ig) D-positive, CD38 medium, CD10-positive); naive (CD19-positive, IgD-positive, CD38 medium, CD27-negative); pre-switch memory (CD19-positive, CD27-positive, IgD-positive); post-switch memory (CD19-positive, CD27-positive, IgD-negative); IgG-positive class-switched (CD19-positive, IgG-positive); IgA-positive class-switched (CD19-positive, IgA-positive); double-negative memory (CD19-positive, IgD-negative, CD27-negative); and plasmablasts (CD19-positive, IgD-negative, CD38 high, CD27 high). Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=196 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants With Early Remission Naive B-cell compartment (n=196)	61.1 percentage of B-cells Interval 5.3 to 102.9
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants With Early Remission Transitional B-cells (n=196)	1.4 percentage of B-cells Interval 0.1 to 18.8
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants With Early Remission Naive B-cells (n=196)	58.1 percentage of B-cells Interval 3.4 to 94.2
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants With Early Remission Memory including double-negative (n=46)	56.4 percentage of B-cells Interval 20.2 to 103.5
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants With Early Remission Memory excluding double-negative (n=194)	46.5 percentage of B-cells Interval 5.6 to 125.8
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants With Early Remission Pre-switch memory B-cells (n=196)	11.1 percentage of B-cells Interval 1.3 to 73.6
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants With Early Remission Post-switch memory B-cells (n=196)	16.4 percentage of B-cells Interval 0.8 to 58.1
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants With Early Remission IgG-positive class-switched B-cells (n=195)	9.9 percentage of B-cells Interval 0.3 to 42.0
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants With Early Remission IgA-positive class-switched B-cells (n=194)	7.4 percentage of B-cells Interval 0.7 to 35.6
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants With Early Remission Double-negative B-cells (n=46)	6.1 percentage of B-cells Interval 2.5 to 16.3
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants With Early Remission Plasmablasts (n=196)	0.3 percentage of B-cells Interval 0.0 to 19.9

SECONDARY outcome

Timeframe: Baseline

Population: ITT2 Population. Participants with evaluable data at the designated visit (number shown = n) were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=197 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants Treated With 8 Courses of Tocilizumab Naive B-cell compartment (n=197)	57.1 percentage of B-cells Interval 5.6 to 91.2
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants Treated With 8 Courses of Tocilizumab Transitional B-cells (n=197)	1.3 percentage of B-cells Interval 0.0 to 13.4
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants Treated With 8 Courses of Tocilizumab Naive B-cells (n=197)	55.5 percentage of B-cells Interval 4.7 to 87.1
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants Treated With 8 Courses of Tocilizumab Memory including double-negative (n=57)	63.2 percentage of B-cells Interval 18.8 to 113.7
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants Treated With 8 Courses of Tocilizumab Memory excluding double-negative (n=196)	49.7 percentage of B-cells Interval 10.9 to 120.1
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants Treated With 8 Courses of Tocilizumab Pre-switch memory B-cells (n=197)	11.6 percentage of B-cells Interval 0.9 to 74.1
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants Treated With 8 Courses of Tocilizumab Post-switch memory B-cells (n=197)	17.2 percentage of B-cells Interval 2.8 to 52.7
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants Treated With 8 Courses of Tocilizumab IgG-positive class-switched B-cells (n=196)	10 percentage of B-cells Interval 0.2 to 38.4
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants Treated With 8 Courses of Tocilizumab IgA-positive class-switched B-cells (n=196)	8.0 percentage of B-cells Interval 1.4 to 34.4
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants Treated With 8 Courses of Tocilizumab Double-negative B-cells (n=57)	6.6 percentage of B-cells Interval 1.2 to 19.1
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants Treated With 8 Courses of Tocilizumab Plasmablasts (n=197)	0.3 percentage of B-cells Interval 0.0 to 7.6

SECONDARY outcome

Timeframe: Baseline

Population: ITT3 Population. Participants with evaluable data at the designated visit (number shown = n) were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=25 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Nonresponding Participants Treated With Rituximab Naive B-cell compartment (n=25)	65.9 percentage of B-cells Interval 9.8 to 85.0
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Nonresponding Participants Treated With Rituximab Transitional B-cells (n=25)	1.6 percentage of B-cells Interval 0.2 to 7.0
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Nonresponding Participants Treated With Rituximab Naive B-cells (n=25)	61.9 percentage of B-cells Interval 5.8 to 83.4
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Nonresponding Participants Treated With Rituximab Memory including double-negative (n=4)	45.1 percentage of B-cells Interval 37.1 to 86.7
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Nonresponding Participants Treated With Rituximab Memory excluding double-negative (n=25)	41.5 percentage of B-cells Interval 21.6 to 139.6
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Nonresponding Participants Treated With Rituximab Pre-switch memory B-cells (n=25)	9.1 percentage of B-cells Interval 2.4 to 36.2
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Nonresponding Participants Treated With Rituximab Post-switch memory B-cells (n=25)	16.1 percentage of B-cells Interval 6.9 to 64.1
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Nonresponding Participants Treated With Rituximab IgG-positive class-switched B-cells (n=25)	8.7 percentage of B-cells Interval 5.0 to 32.7
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Nonresponding Participants Treated With Rituximab IgA-positive class-switched B-cells (n=25)	7.7 percentage of B-cells Interval 3.4 to 29.3
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Nonresponding Participants Treated With Rituximab Double-negative B-cells (n=4)	7.5 percentage of B-cells Interval 5.9 to 9.1
Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Nonresponding Participants Treated With Rituximab Plasmablasts (n=25)	0.3 percentage of B-cells Interval 0.0 to 3.2

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: ITT1 Population; n = number of data pairs included in the analysis.

Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional, naïve, pre-switch memory, post-switch memory, IgG-positive class-switched, IgA-positive class-switched, double-negative memory, and plasmablasts. Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined. Extent of disease response, using change from Baseline to Week 16 in DAS28 score, was correlated to the percentage of B-cells within each subpopulation at Baseline. Correlation is indicated by a correlation coefficient (r) \>0.2, with greater values indicating a stronger correlation.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=192 Pairs All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Week 16 Among Participants With Early Remission Naive B-cell compartment (n=192)	-0.02258 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Week 16 Among Participants With Early Remission Transitional B-cells (n=192)	-0.00949 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Week 16 Among Participants With Early Remission Naive B-cells (n=192)	-0.01920 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Week 16 Among Participants With Early Remission Memory B-cells (n=62)	-0.03148 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Week 16 Among Participants With Early Remission Pre-switch memory B-cells (n=192)	0.03221 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Week 16 Among Participants With Early Remission Post-switch memory B-cells (n=192)	0.05419 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Week 16 Among Participants With Early Remission IgG-positive class-switched B-cells (n=192)	0.08864 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Week 16 Among Participants With Early Remission IgA-positive class-switched B-cells (n=192)	0.01041 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Week 16 Among Participants With Early Remission Double-negative B-cells (n=62)	-0.02134 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Week 16 Among Participants With Early Remission Plasmablasts (n=192)	0.00397 coefficient

SECONDARY outcome

Timeframe: Baseline and Weeks 16, 24, and 32

Population: ITT2 Population; n = number of data pairs included in the analysis.

Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional, naïve, pre-switch memory, post-switch memory, IgG-positive class-switched, IgA-positive class-switched, double-negative memory, and plasmablasts. Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined. Extent of disease response, using change from Baseline in DAS28 score, was correlated to the percentage of B-cells within each subpopulation at Baseline. Correlation is indicated by a correlation coefficient (r) \>0.2, with greater values indicating a stronger correlation.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=199 Pairs All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 16, Naive B-cell compartment (n=199)	0.00007 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 16, Transitional B-cells (n=199)	-0.06529 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 16, Naive B-cells (n=199)	0.02334 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 16, Memory B-cells (n=75)	0.03478 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 16, Pre-switch memory B-cells (n=199)	-0.01889 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 16, Post-switch memory B-cells (n=199)	-0.04161 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 16, IgG-positive class-switched (n=199)	-0.06235 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 16, IgA-positive class-switched (n=199)	-0.06492 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 16, Double-negative B-cells (n=75)	-0.04352 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 16, Plasmablasts (n=199)	-0.13161 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24, Naive B-cell compartment (n=162)	-0.18469 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24, Transitional B-cells (n=162)	-0.21966 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24, Naive B-cells (n=162)	-0.15683 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24, Memory B-cells (n=76)	0.15135 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24, Pre-switch memory B-cells (n=162)	0.08074 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24, Post-switch memory B-cells (n=162)	0.10798 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24, IgG-positive class-switched (n=161)	0.10752 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24, IgA-positive class-switched (n=162)	0.11023 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24, Double-negative B-cells (n=76)	0.05609 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 24, Plasmablasts (n=162)	0.07468 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32, Naive B-cell compartment (n=179)	-0.12635 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32, Transitional B-cells (n=179)	-0.09234 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32, Naive B-cells (n=179)	-0.11114 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32, Memory B-cells (n=88)	0.05361 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32, Pre-switch memory B-cells (n=179)	0.12265 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32, Post-switch memory B-cells (n=179)	0.05867 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32, IgG-positive class-switched (n=181)	0.06381 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32, IgA-positive class-switched (n=181)	0.06036 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32, Double-negative B-cells (n=90)	-0.06310 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab Week 32, Plasmablasts (n=179)	0.02205 coefficient

SECONDARY outcome

Timeframe: Baseline and Weeks 16, 32, 40, 48, and 66

Population: ITT3 Population; n = number of data pairs included in the analysis.

Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional, naïve, pre-switch memory, post-switch memory, IgG-positive class-switched, IgA-positive class-switched, double-negative memory, and plasmablasts. Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined. Extent of disease response, using change from Baseline in DAS28 score, was correlated to the percentage of B-cells within each subpopulation at Baseline. Correlation is indicated by a correlation coefficient (r) \>0.2, with greater values indicating a stronger correlation.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=24 Pairs All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 16, Naive B-cell compartment (n=24)	0.09611 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 16, Transitional B-cells (n=24)	0.08571 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 16, Naive B-cells (n=24)	0.00870 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 16, Memory B-cells (n=6)	-0.60000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 16, Pre-switch memory B-cells (n=24)	-0.15217 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 16, Post-switch memory B-cells (n=24)	-0.04004 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 16, IgG-positive class-switched (n=24)	-0.07528 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 16, IgA-positive class-switched (n=24)	0.27049 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 16, Double-negative B-cells (n=6)	-0.14286 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 16, Plasmablasts (n=24)	0.13232 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 32, Naive B-cell compartment (n=0)	NA coefficient Participants in this population were followed for changes in DAS28 up to Week 16 compared to Baseline, and for changes up to Week 66 compared to Week 16. Thus, change from Baseline to Week 32 was not determined.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 32, Transitional B-cells (n=0)	NA coefficient Participants in this population were followed for changes in DAS28 up to Week 16 compared to Baseline, and for changes up to Week 66 compared to Week 16. Thus, change from Baseline to Week 32 was not determined.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 32, Naive B-cells (n=0)	NA coefficient Participants in this population were followed for changes in DAS28 up to Week 16 compared to Baseline, and for changes up to Week 66 compared to Week 16. Thus, change from Baseline to Week 32 was not determined.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 32, Memory B-cells (n=0)	NA coefficient Participants in this population were followed for changes in DAS28 up to Week 16 compared to Baseline, and for changes up to Week 66 compared to Week 16. Thus, change from Baseline to Week 32 was not determined.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 32, Pre-switch memory B-cells (n=0)	NA coefficient Participants in this population were followed for changes in DAS28 up to Week 16 compared to Baseline, and for changes up to Week 66 compared to Week 16. Thus, change from Baseline to Week 32 was not determined.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 32, Post-switch memory B-cells (n=0)	NA coefficient Participants in this population were followed for changes in DAS28 up to Week 16 compared to Baseline, and for changes up to Week 66 compared to Week 16. Thus, change from Baseline to Week 32 was not determined.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 32, IgG-positive class-switched (n=0)	NA coefficient Participants in this population were followed for changes in DAS28 up to Week 16 compared to Baseline, and for changes up to Week 66 compared to Week 16. Thus, change from Baseline to Week 32 was not determined.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 32, IgA-positive class-switched (n=0)	NA coefficient Participants in this population were followed for changes in DAS28 up to Week 16 compared to Baseline, and for changes up to Week 66 compared to Week 16. Thus, change from Baseline to Week 32 was not determined.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 32, Double-negative B-cells (n=0)	NA coefficient Participants in this population were followed for changes in DAS28 up to Week 16 compared to Baseline, and for changes up to Week 66 compared to Week 16. Thus, change from Baseline to Week 32 was not determined.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 32, Plasmablasts (n=0)	NA coefficient Participants in this population were followed for changes in DAS28 up to Week 16 compared to Baseline, and for changes up to Week 66 compared to Week 16. Thus, change from Baseline to Week 32 was not determined.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 40, Naive B-cell compartment (n=2)	1.00000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 40, Transitional B-cells (n=2)	-1.00000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 40, Naive B-cells (n=2)	1.00000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 40, Memory B-cells (n=0)	NA coefficient Unable to calculate because the number of pairs was 0 at this assessment.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 40, Pre-switch memory B-cells (n=2)	1.00000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 40, Post-switch memory B-cells (n=2)	1.00000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 40, IgG-positive class-switched (n=2)	1.00000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 40, IgA-positive class-switched (n=2)	1.00000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 40, Double-negative B-cells (n=0)	NA coefficient Unable to calculate because the number of pairs was 0 at this assessment.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 40, Plasmablasts (n=2)	1.00000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 48, Naive B-cell compartment (n=5)	0.30000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 48, Transitional B-cells (n=5)	-0.60000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 48, Naive B-cells (n=5)	0.30000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 48, Memory B-cells (n=1)	NA coefficient Unable to calculate because the number of pairs was 1 at this assessment.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 48, Pre-switch memory B-cells (n=5)	0.60000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 48, Post-switch memory B-cells (n=5)	0.20000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 48, IgG-positive class-switched (n=5)	0.20000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 48, IgA-positive class-switched (n=5)	0.50000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 48, Double-negative B-cells (n=1)	NA coefficient Unable to calculate because the number of pairs was 1 at this assessment.
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 48, Plasmablasts (n=5)	0.10000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 66, Naive B-cell compartment (n=10)	0.12727 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 66, Transitional B-cells (n=10)	-0.03030 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 66, Naive B-cells (n=10)	0.04242 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 66, Memory B-cells (n=3)	1.00000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 66, Pre-switch memory B-cells (n=10)	-0.03030 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 66, Post-switch memory B-cells (n=10)	0.16364 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 66, IgG-positive class-switched (n=10)	0.07295 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 66, IgA-positive class-switched (n=10)	0.12805 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 66, Double-negative B-cells (n=3)	1.00000 coefficient
Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab Week 66, Plasmablasts (n=10)	0.30909 coefficient

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Main ITT Population. Employed participants with evaluable data at the designated visit (number shown = n) were included.

Work days missed were documented by reason (either rheumatoid arthritis \[RA\] or other reasons) for each participant over the preceding 7-day period. The mean number of work days missed was calculated by averaging the number of days missed per week among all participants.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=241 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Mean Number of Work Days Missed Per Week Due to RA, Baseline (n=241)	1.03 days Standard Deviation 2.30
Mean Number of Work Days Missed Per Week Due to RA, Week 16 (n=221)	0.39 days Standard Deviation 1.51
Mean Number of Work Days Missed Per Week Due to other reasons, Baseline (n=233)	0.14 days Standard Deviation 0.87
Mean Number of Work Days Missed Per Week Due to other reasons, Week 16 (n=222)	0.32 days Standard Deviation 1.26

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included.

The SF-36 evaluates participant-rated quality of life using 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for each section is the average of the individual question scores, which are scaled from 0 to 100, with higher scores indicating better functioning. The mean score at each timepoint was determined by averaging the scores among all participants.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=513 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Quality of Life as Assessed Using Short Form 36 (SF-36) Physical functioning, Baseline (n=511)	49.6 units on a scale Standard Deviation 23.7
Quality of Life as Assessed Using Short Form 36 (SF-36) Physical functioning, Week 16 (n=473)	64.1 units on a scale Standard Deviation 25.5
Quality of Life as Assessed Using Short Form 36 (SF-36) Role (physical), Baseline (n=508)	12.9 units on a scale Standard Deviation 18.1
Quality of Life as Assessed Using Short Form 36 (SF-36) Role (physical), Week 16 (n=472)	29.9 units on a scale Standard Deviation 21.4
Quality of Life as Assessed Using Short Form 36 (SF-36) Bodily pain, Baseline (n=512)	31.3 units on a scale Standard Deviation 18.2
Quality of Life as Assessed Using Short Form 36 (SF-36) Bodily pain, Week 16 (n=474)	55.3 units on a scale Standard Deviation 17.8
Quality of Life as Assessed Using Short Form 36 (SF-36) General health, Baseline (n=504)	43.6 units on a scale Standard Deviation 16.7
Quality of Life as Assessed Using Short Form 36 (SF-36) General health, Week 16 (n=468)	54.3 units on a scale Standard Deviation 18.3
Quality of Life as Assessed Using Short Form 36 (SF-36) Vitality, Baseline (n=512)	44.0 units on a scale Standard Deviation 19.7
Quality of Life as Assessed Using Short Form 36 (SF-36) Vitality, Week 16 (n=474)	58.1 units on a scale Standard Deviation 20.4
Quality of Life as Assessed Using Short Form 36 (SF-36) Social functioning, Baseline (n=507)	68.1 units on a scale Standard Deviation 24.8
Quality of Life as Assessed Using Short Form 36 (SF-36) Social functioning, Week 16 (n=464)	80.1 units on a scale Standard Deviation 21.6
Quality of Life as Assessed Using Short Form 36 (SF-36) Role (emotional), Baseline (n=505)	55.9 units on a scale Standard Deviation 45.0
Quality of Life as Assessed Using Short Form 36 (SF-36) Role (emotional), Week 16 (n=472)	70.9 units on a scale Standard Deviation 42.1
Quality of Life as Assessed Using Short Form 36 (SF-36) Mental health, Baseline (n=513)	63.5 units on a scale Standard Deviation 18.7
Quality of Life as Assessed Using Short Form 36 (SF-36) Mental health, Week 16 (n=474)	72.3 units on a scale Standard Deviation 17.9

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=470 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change From Baseline in Quality of Life as Assessed Using SF-36 at Week 16 Physical functioning (n=466)	14.3 units on a scale Standard Deviation 21.8
Change From Baseline in Quality of Life as Assessed Using SF-36 at Week 16 Role (physical) (n=461)	17.0 units on a scale Standard Deviation 22.0
Change From Baseline in Quality of Life as Assessed Using SF-36 at Week 16 Bodily pain (n=470)	23.9 units on a scale Standard Deviation 21.1
Change From Baseline in Quality of Life as Assessed Using SF-36 at Week 16 General health (n=454)	10.4 units on a scale Standard Deviation 18.5
Change From Baseline in Quality of Life as Assessed Using SF-36 at Week 16 Vitality (n=468)	13.9 units on a scale Standard Deviation 19.3
Change From Baseline in Quality of Life as Assessed Using SF-36 at Week 16 Social functioning (n=456)	12.0 units on a scale Standard Deviation 23.8
Change From Baseline in Quality of Life as Assessed Using SF-36 at Week 16 Role (emotional) (n=459)	14.7 units on a scale Standard Deviation 46.1
Change From Baseline in Quality of Life as Assessed Using SF-36 at Week 16 Mental health (n=468)	8.7 units on a scale Standard Deviation 16.8

SECONDARY outcome

Timeframe: Weeks 16 and 32

Population: ITT2 Population. Participants with evaluable data at the designated visit (number shown = n) were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=188 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Participants Treated With 8 Courses of Tocilizumab Social functioning (n=184)	-0.3 units on a scale Standard Deviation 19.6
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Participants Treated With 8 Courses of Tocilizumab Role (emotional) (n=184)	5.5 units on a scale Standard Deviation 42.3
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Participants Treated With 8 Courses of Tocilizumab Mental health (n=186)	0.7 units on a scale Standard Deviation 15.3
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Participants Treated With 8 Courses of Tocilizumab Physical functioning (n=188)	3.6 units on a scale Standard Deviation 16.6
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Participants Treated With 8 Courses of Tocilizumab Role (physical) (n=187)	2.0 units on a scale Standard Deviation 20.6
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Participants Treated With 8 Courses of Tocilizumab Bodily pain (n=188)	3.2 units on a scale Standard Deviation 16.5
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Participants Treated With 8 Courses of Tocilizumab General health (n=184)	2.6 units on a scale Standard Deviation 14.3
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Participants Treated With 8 Courses of Tocilizumab Vitality (n=186)	2.7 units on a scale Standard Deviation 14.2

SECONDARY outcome

Timeframe: Weeks 16 and 32

Population: ITT3 Population. Participants with evaluable data at the designated visit (number shown = n) were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=26 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Nonresponding Participants Treated With Rituximab Role (emotional) (n=24)	2.8 units on a scale Standard Deviation 35.3
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Nonresponding Participants Treated With Rituximab Social functioning (n=24)	-3.1 units on a scale Standard Deviation 17.4
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Nonresponding Participants Treated With Rituximab Mental health (n=26)	3.4 units on a scale Standard Deviation 10.7
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Nonresponding Participants Treated With Rituximab Physical functioning (n=26)	2.5 units on a scale Standard Deviation 20.0
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Nonresponding Participants Treated With Rituximab Role (physical) (n=24)	-1.0 units on a scale Standard Deviation 21.5
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Nonresponding Participants Treated With Rituximab Bodily pain (n=26)	10.6 units on a scale Standard Deviation 20.8
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Nonresponding Participants Treated With Rituximab General health (n=24)	5.2 units on a scale Standard Deviation 18.1
Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Nonresponding Participants Treated With Rituximab Vitality (n=26)	1.0 units on a scale Standard Deviation 9.3

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included.

The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. The mean index score at each timepoint was determined by averaging the scores among all participants.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=513 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Quality of Life as Assessed Using HAQ-DI Baseline (n=513)	1.24 units on a scale Standard Deviation 0.67
Quality of Life as Assessed Using HAQ-DI Week 16 (n=472)	0.75 units on a scale Standard Deviation 0.67

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Main ITT Population. Participants with evaluable data at the designated visit were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=466 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change From Baseline in Quality of Life as Assessed Using HAQ-DI at Week 16	-0.48 units on a scale Standard Deviation 0.58

SECONDARY outcome

Timeframe: Weeks 16 and 32

Population: ITT2 Population. Participants with evaluable data at the designated visit were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=187 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change From Week 16 to 32 in Quality of Life as Assessed Using HAQ-DI Among Participants Treated With 8 Courses of Tocilizumab	-0.06 units on a scale Standard Deviation 0.34

SECONDARY outcome

Timeframe: Weeks 16 and 32

Population: ITT3 Population. Participants with evaluable data at the designated visit were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=26 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change From Week 16 to 32 in Quality of Life as Assessed Using HAQ-DI Among Nonresponding Participants Treated With Rituximab	-0.10 units on a scale Standard Deviation 0.39

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Main ITT Population

The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. Response was defined as a change in index score \>0.22 from Baseline to Week 16.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=519 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Percentage of Participants Achieving a Response According to HAQ-DI Criteria	61.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included.

The FACIT-F evaluates quality of life using 5 categories: physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and fatigue (FS). Participants answer each item on a 5-point scale from 0 to 4. The total score is the sum of individual responses across all 5 categories and may range from 0 to 160. The FACIT-General (FACIT-G; range 0 to 108) is the sum of scores for PWB, SWB, EWB, and FWB; the FACIT-Fatigue (FACIT-F) trial outcome index (TOI; range 0 to 108) is the sum of scores for PWB, FWB, and FS; and the FACIT-F fatigue (range 0 to 52) is the sum of scores for the FS only. For derivations of the FACIT-F reported here, higher scores indicate better quality of life. The mean score at each timepoint was determined by averaging scores among all participants.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=510 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Quality of Life as Assessed Using Functional Assessment of Chronic Illness Therapy (FACIT) FACIT-F TOI, Baseline (n=498)	66.2 units on a scale Standard Deviation 20.6
Quality of Life as Assessed Using Functional Assessment of Chronic Illness Therapy (FACIT) FACIT-F TOI, Week 16 (n=460)	80.8 units on a scale Standard Deviation 19.3
Quality of Life as Assessed Using Functional Assessment of Chronic Illness Therapy (FACIT) FACIT-G total, Baseline (n=498)	71.1 units on a scale Standard Deviation 15.7
Quality of Life as Assessed Using Functional Assessment of Chronic Illness Therapy (FACIT) FACIT-G total, Week 16 (n=462)	82.6 units on a scale Standard Deviation 15.9
Quality of Life as Assessed Using Functional Assessment of Chronic Illness Therapy (FACIT) FACIT-F total, Baseline (n=494)	103.8 units on a scale Standard Deviation 25.5
Quality of Life as Assessed Using Functional Assessment of Chronic Illness Therapy (FACIT) FACIT-F total, Week 16 (n=458)	121.9 units on a scale Standard Deviation 25.3
Quality of Life as Assessed Using Functional Assessment of Chronic Illness Therapy (FACIT) FACIT-F fatigue, Baseline (n=510)	32.7 units on a scale Standard Deviation 11.6
Quality of Life as Assessed Using Functional Assessment of Chronic Illness Therapy (FACIT) FACIT-F fatigue, Week 16 (n=475)	39.2 units on a scale Standard Deviation 10.6

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Main ITT Population. Participants with evaluable data at the designated visit (number shown = n) were included.

The FACIT-F evaluates quality of life using 5 categories: PWB, SWB, EWB, FWB, and FS. Participants answer each item on a 5-point scale from 0 to 4. The total score is the sum of individual responses across all 5 categories and may range from 0 to 160. The FACIT-G (range 0 to 108) is the sum of scores for PWB, SWB, EWB, and FWB; the FACIT-F TOI (range 0 to 108) is the sum of scores for PWB, FWB, and FS; and the FACIT-F fatigue (range 0 to 52) is the sum of scores for the FS only. For derivations of the FACIT-F reported here, higher scores indicate better quality of life. The mean score at each timepoint was determined by averaging scores among all participants, and the change in score was calculated as \[mean score at Week 16 minus mean score at Baseline\].

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=467 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change From Baseline in Quality of Life as Assessed Using FACIT at Week 16 FACIT-F TOI (n=445)	14.2 units on a scale Standard Deviation 17.9
Change From Baseline in Quality of Life as Assessed Using FACIT at Week 16 FACIT-G total (n=445)	10.8 units on a scale Standard Deviation 13.6
Change From Baseline in Quality of Life as Assessed Using FACIT at Week 16 FACIT-F total (n=439)	17.5 units on a scale Standard Deviation 21.8
Change From Baseline in Quality of Life as Assessed Using FACIT at Week 16 FACIT-F fatigue (n=467)	6.6 units on a scale Standard Deviation 9.9

SECONDARY outcome

Timeframe: Weeks 16 and 32

Population: ITT2 Population. Participants with evaluable data at the designated visit (number shown = n) were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=186 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Participants Treated With 8 Courses of Tocilizumab FACIT-F TOI (n=172)	1.7 units on a scale Standard Deviation 12.9
Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Participants Treated With 8 Courses of Tocilizumab FACIT-G total (n=174)	1.1 units on a scale Standard Deviation 9.2
Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Participants Treated With 8 Courses of Tocilizumab FACIT-F total (n=170)	2.0 units on a scale Standard Deviation 15.1
Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Participants Treated With 8 Courses of Tocilizumab FACIT-F fatigue (n=186)	0.8 units on a scale Standard Deviation 7.4

SECONDARY outcome

Timeframe: Weeks 16 and 32

Population: ITT3 Population. Participants with evaluable data at the designated visit were included.

Outcome measures

Outcome measures
Measure	TCZ/TCZ or TCZ/RTX n=26 Participants All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Nonresponding Participants Treated With Rituximab FACIT-F TOI	2.9 units on a scale Standard Deviation 9.8
Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Nonresponding Participants Treated With Rituximab FACIT-G total	3.0 units on a scale Standard Deviation 8.3
Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Nonresponding Participants Treated With Rituximab FACIT-F total	4.4 units on a scale Standard Deviation 12.5
Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Nonresponding Participants Treated With Rituximab FACIT-F fatigue	1.4 units on a scale Standard Deviation 5.8

Adverse Events

TCZ/TCZ or TCZ/RTX

Serious events: 54 serious events

Other events: 104 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	TCZ/TCZ or TCZ/RTX n=519 participants at risk All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Blood and lymphatic system disorders Leukopenia	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Blood and lymphatic system disorders Neutropenia	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Blood and lymphatic system disorders Thrombocytopenia	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Cardiac disorders Acute myocardial infarction	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Cardiac disorders Atrial fibrillation	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Cardiac disorders Atrioventricular block complete	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Cardiac disorders Coronary artery disease	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Cardiac disorders Myocardial infarction	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Gastrointestinal disorders Abdominal pain	0.39% 2/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Gastrointestinal disorders Abdominal pain lower	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Gastrointestinal disorders Diarrhoea	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Gastrointestinal disorders Gastrointestinal perforation	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Gastrointestinal disorders Gastrooesophageal reflux disease	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
General disorders Fatigue	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
General disorders Oedema peripheral	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Immune system disorders Hypersensitivity	0.39% 2/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Infections and infestations Bronchitis	0.58% 3/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Infections and infestations Diverticulitis	0.39% 2/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Infections and infestations Pneumonia	0.39% 2/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Infections and infestations Abscess limb	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Infections and infestations Anal abscess	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Infections and infestations Gangrene	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Infections and infestations Infection	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Infections and infestations Localised infection	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Infections and infestations Lower respiratory tract infection bacterial	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Infections and infestations Respiratory tract infection	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Infections and infestations Tonsillitis	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Infections and infestations Wound infection	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Injury, poisoning and procedural complications Fall	0.39% 2/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Injury, poisoning and procedural complications Contusion	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Injury, poisoning and procedural complications Craniocerebral injury	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Injury, poisoning and procedural complications Infusion related reaction	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Injury, poisoning and procedural complications Joint dislocation	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Injury, poisoning and procedural complications Overdose	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Injury, poisoning and procedural complications Road traffic accident	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Injury, poisoning and procedural complications Tendon rupture	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Injury, poisoning and procedural complications Wound	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Injury, poisoning and procedural complications Hip fracture	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Injury, poisoning and procedural complications Lower limb fracture	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Investigations Alanine aminotransferase increased	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Investigations Fibrin D dimer increased	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Investigations Liver function test abnormal	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Musculoskeletal and connective tissue disorders Bursitis	0.58% 3/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.39% 2/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Musculoskeletal and connective tissue disorders Joint destruction	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Musculoskeletal and connective tissue disorders Osteoarthritis	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Musculoskeletal and connective tissue disorders Sacroiliitis	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal squamous cell carcinoma	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Nervous system disorders Dizziness	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Nervous system disorders Intracranial haematoma	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Nervous system disorders Migraine	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Renal and urinary disorders Haematuria	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Renal and urinary disorders Nephrolithiasis	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Renal and urinary disorders Urinary retention	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Respiratory, thoracic and mediastinal disorders Allergic cough	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Respiratory, thoracic and mediastinal disorders Asthma	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Respiratory, thoracic and mediastinal disorders Hyperventilation	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Vascular disorders Haematoma	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Vascular disorders Hypertension	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Vascular disorders Hypertensive crisis	0.19% 1/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).

Other adverse events

Other adverse events
Measure	TCZ/TCZ or TCZ/RTX n=519 participants at risk All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of \<2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score \>1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score \>3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.
Infections and infestations Nasopharyngitis	14.8% 77/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).
Vascular disorders Hypertension	5.8% 30/519 • Up to 66 weeks Adverse events (AEs) were assessed at each treatment visit from Baseline to Week 16, at which point participants having achieved early remission completed the study. Those who did not achieve early remission continued to receive treatment, and AEs were assessed until 4 weeks after last dose (TCZ/TCZ) or until Week 66 (TCZ/RTX).

Additional Information

Medical Communications

Hoffmann-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