Trial Outcomes & Findings for A Study of Tocilizumab (RoActemra/Actemra) in Monotherapy or in Combination With Methotrexate or Other Non-Biologic DMARDs in Participants With Active Rheumatoid Arthritis and an Inadequate Response to Current Non-Biologic DMARD Therapy or the First Anti-TNF Biologic Agent (NCT NCT02046603)

NCT ID: NCT02046603

Last Updated: 2018-12-07

Results Overview

DAS28 was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, erythrocyte sedimentation rate (ESR; millimeters per hour \[mm/hour\]), and patient's global assessment of disease activity (measured on a 0 to 100 mm Visual Analog Scale \[VAS\] where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR greater than or equal to (≥) 2.6 to less than or equal to (≤) 3.2 implied low disease activity, greater than (\>) 3.2 to ≤5.1 implied moderate disease activity, \>5.1 implied high/severe disease, and less than (\<) 2.6 implied clinical remission.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 162 participants
• Primary outcome timeframe: Baseline, Week 2
• Results posted on: 2018-12-07

Participant Flow

A total of 162 participants were enrolled. One participant who did not receive a dose of tocilizumab was excluded from the full analysis set (FAS) and the results are reported for 161 participants.

Participant milestones

Measure	Tocilizumab Monotherapy Participants received a weekly subcutaneous (SC) injection of tocilizumab 162 milligrams (mg) as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic disease modifying anti-rheumatic drugs (DMARDs) for 52 weeks.
Overall Study STARTED	22	140
Overall Study Received at Least 1 Dose of Tocilizumab	21	140
Overall Study COMPLETED	7	65
Overall Study NOT COMPLETED	15	75

Reasons for withdrawal

Measure	Tocilizumab Monotherapy Participants received a weekly subcutaneous (SC) injection of tocilizumab 162 milligrams (mg) as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic disease modifying anti-rheumatic drugs (DMARDs) for 52 weeks.
Overall Study Other	11	66
Overall Study Protocol Violation	0	1
Overall Study Participant/legal guardian decision	1	3
Overall Study Physician Decision	2	1
Overall Study Lost to Follow-up	1	2
Overall Study Death	0	1
Overall Study Adverse Event	0	1

Baseline Characteristics

A Study of Tocilizumab (RoActemra/Actemra) in Monotherapy or in Combination With Methotrexate or Other Non-Biologic DMARDs in Participants With Active Rheumatoid Arthritis and an Inadequate Response to Current Non-Biologic DMARD Therapy or the First Anti-TNF Biologic Agent

Baseline characteristics by cohort

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=140 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.	Total n=161 Participants Total of all reporting groups
Age, Continuous	53.9 years STANDARD_DEVIATION 13.63 • n=5 Participants	55.3 years STANDARD_DEVIATION 10.76 • n=7 Participants	55.1 years STANDARD_DEVIATION 11.14 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	104 Participants n=7 Participants	120 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	36 Participants n=7 Participants	41 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 2

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

DAS28 was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, erythrocyte sedimentation rate (ESR; millimeters per hour [mm/hour]), and patient's global assessment of disease activity (measured on a 0 to 100 mm Visual Analog Scale [VAS] where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR greater than or equal to (≥) 2.6 to less than or equal to (≤) 3.2 implied low disease activity, greater than (>) 3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and less than (<) 2.6 implied clinical remission.

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=139 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 2 Baseline	5.52 units on a scale Standard Deviation 1.014	5.53 units on a scale Standard Deviation 1.257
Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 2 Change at Week 2	-1.41 units on a scale Standard Deviation 0.994	-1.22 units on a scale Standard Deviation 1.131

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=137 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in DAS28-ESR at Week 4	-1.86 units on a scale Standard Deviation 1.016	-2.11 units on a scale Standard Deviation 1.215

PRIMARY outcome

Timeframe: Baseline, Week 8

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

Outcome measures

Measure	Tocilizumab Monotherapy n=18 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=131 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in DAS28-ESR at Week 8	-2.42 units on a scale Standard Deviation 1.352	-2.62 units on a scale Standard Deviation 1.482

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

Outcome measures

Measure	Tocilizumab Monotherapy n=19 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=128 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in DAS28-ESR at Week 12	-2.33 units on a scale Standard Deviation 1.522	-2.99 units on a scale Standard Deviation 1.510

PRIMARY outcome

Timeframe: Baseline, Week 16

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

Outcome measures

Measure	Tocilizumab Monotherapy n=18 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=125 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in DAS28-ESR at Week 16	-2.93 units on a scale Standard Deviation 1.218	-3.07 units on a scale Standard Deviation 1.532

PRIMARY outcome

Timeframe: Baseline, Week 20

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

Outcome measures

Measure	Tocilizumab Monotherapy n=19 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=121 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in DAS28-ESR at Week 20	-3.17 units on a scale Standard Deviation 1.346	-3.13 units on a scale Standard Deviation 1.525

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

Outcome measures

Measure	Tocilizumab Monotherapy n=19 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=117 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in DAS28-ESR at Week 24	-3.28 units on a scale Standard Deviation 1.379	-3.33 units on a scale Standard Deviation 1.470

PRIMARY outcome

Timeframe: Baseline, Week 28

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

Outcome measures

Measure	Tocilizumab Monotherapy n=19 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=115 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in DAS28-ESR at Week 28	-3.54 units on a scale Standard Deviation 1.260	-3.32 units on a scale Standard Deviation 1.552

PRIMARY outcome

Timeframe: Baseline, Week 32

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

Outcome measures

Measure	Tocilizumab Monotherapy n=19 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=115 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in DAS28-ESR at Week 32	-3.19 units on a scale Standard Deviation 1.418	-3.54 units on a scale Standard Deviation 1.448

PRIMARY outcome

Timeframe: Baseline, Week 36

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

Outcome measures

Measure	Tocilizumab Monotherapy n=18 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=114 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in DAS28-ESR at Week 36	-3.57 units on a scale Standard Deviation 1.358	-3.55 units on a scale Standard Deviation 1.589

PRIMARY outcome

Timeframe: Baseline, Week 40

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

Outcome measures

Measure	Tocilizumab Monotherapy n=17 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=111 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in DAS28-ESR at Week 40	-3.82 units on a scale Standard Deviation 1.143	-3.64 units on a scale Standard Deviation 1.524

PRIMARY outcome

Timeframe: Baseline, Week 44

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

Outcome measures

Measure	Tocilizumab Monotherapy n=17 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=107 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in DAS28-ESR at Week 44	-3.61 units on a scale Standard Deviation 1.325	-3.65 units on a scale Standard Deviation 1.574

PRIMARY outcome

Timeframe: Baseline, Week 48

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

Outcome measures

Measure	Tocilizumab Monotherapy n=16 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=107 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in DAS28-ESR at Week 48	-3.54 units on a scale Standard Deviation 1.146	-3.65 units on a scale Standard Deviation 1.552

PRIMARY outcome

Timeframe: Baseline, Week 52

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

Outcome measures

Measure	Tocilizumab Monotherapy n=15 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=107 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in DAS28-ESR at Week 52	-3.75 units on a scale Standard Deviation 1.361	-3.67 units on a scale Standard Deviation 1.592

PRIMARY outcome

Timeframe: Baseline, early withdrawal (up to Week 52)

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

Outcome measures

Measure	Tocilizumab Monotherapy n=5 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=28 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in DAS28-ESR at Early Withdrawal	-2.88 units on a scale Standard Deviation 1.236	-1.63 units on a scale Standard Deviation 1.480

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

Population: FAS population.

A participant had an ACR20 response if there was at least a 20 percent (%) improvement, ie, reduction from Baseline, in TJC (68 joints) and SJC (66 joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, averaged to 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either C-reactive protein [CRP] or ESR).

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=140 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response Week 2	6 participants	23 participants
Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response Week 4	6 participants	68 participants
Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response Week 8	11 participants	69 participants
Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response Week 12	10 participants	83 participants
Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response Week 16	13 participants	83 participants
Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response Week 20	15 participants	86 participants
Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response Week 24	15 participants	90 participants
Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response Week 28	14 participants	87 participants
Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response Week 32	13 participants	89 participants
Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response Week 36	12 participants	92 participants
Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response Week 40	13 participants	91 participants
Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response Week 44	12 participants	88 participants
Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response Week 48	12 participants	87 participants
Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response Week 52	12 participants	88 participants
Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response Early withdrawal	3 participants	10 participants

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

Population: FAS population.

A participant had an ACR50 response if there was at least a 50% improvement, ie, reduction from Baseline, in TJC (68 joints) and SJC (66 joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, averaged to 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR).

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=140 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Number of Participants Achieving an ACR50 Response Week 2	0 participants	5 participants
Number of Participants Achieving an ACR50 Response Week 4	3 participants	20 participants
Number of Participants Achieving an ACR50 Response Week 8	6 participants	43 participants
Number of Participants Achieving an ACR50 Response Week 12	8 participants	54 participants
Number of Participants Achieving an ACR50 Response Week 16	7 participants	62 participants
Number of Participants Achieving an ACR50 Response Week 20	9 participants	61 participants
Number of Participants Achieving an ACR50 Response Week 24	9 participants	64 participants
Number of Participants Achieving an ACR50 Response Week 28	13 participants	68 participants
Number of Participants Achieving an ACR50 Response Week 32	8 participants	69 participants
Number of Participants Achieving an ACR50 Response Week 36	9 participants	74 participants
Number of Participants Achieving an ACR50 Response Week 40	9 participants	71 participants
Number of Participants Achieving an ACR50 Response Week 44	10 participants	72 participants
Number of Participants Achieving an ACR50 Response Week 48	11 participants	73 participants
Number of Participants Achieving an ACR50 Response Week 52	8 participants	73 participants
Number of Participants Achieving an ACR50 Response Early withdrawal	2 participants	4 participants

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

Population: FAS population.

A participant had an ACR70 response if there was at least a 70% improvement, ie, reduction from Baseline, in TJC (68 joints) and SJC (66 joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, averaged to 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR).

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=140 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Number of Participants Achieving an ACR70 Response Week 48	8 participants	56 participants
Number of Participants Achieving an ACR70 Response Week 2	0 participants	0 participants
Number of Participants Achieving an ACR70 Response Week 4	1 participants	9 participants
Number of Participants Achieving an ACR70 Response Week 8	4 participants	19 participants
Number of Participants Achieving an ACR70 Response Week 12	3 participants	30 participants
Number of Participants Achieving an ACR70 Response Week 16	3 participants	32 participants
Number of Participants Achieving an ACR70 Response Week 20	7 participants	37 participants
Number of Participants Achieving an ACR70 Response Week 24	5 participants	38 participants
Number of Participants Achieving an ACR70 Response Week 28	6 participants	44 participants
Number of Participants Achieving an ACR70 Response Week 32	6 participants	47 participants
Number of Participants Achieving an ACR70 Response Week 36	7 participants	48 participants
Number of Participants Achieving an ACR70 Response Week 40	8 participants	49 participants
Number of Participants Achieving an ACR70 Response Week 44	6 participants	53 participants
Number of Participants Achieving an ACR70 Response Week 52	7 participants	54 participants
Number of Participants Achieving an ACR70 Response Early withdrawal	2 participants	1 participants

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

Population: FAS population.

DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). DAS28-ESR scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. The DAS28-ESR based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline >1.2 with a DAS28 score ≤3.2; moderate responders had a change from baseline >1.2 with a DAS28 score >3.2 or a change from baseline >0.6 to ≤1.2 with a DAS28 score ≤5.1. Participants with change from baseline >0.6 to ≤1.2 with a DAS28 score >5.1, or any score with change from baseline ≤0.6, were assessed as non-responders.

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=140 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 2: No response	4 participants	56 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 2: Moderate response	10 participants	56 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 2: Good response	7 participants	25 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 4: No response	3 participants	22 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 4: Moderate response	7 participants	58 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 4: Good response	11 participants	57 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 8: No response	1 participants	11 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 8: Moderate response	9 participants	48 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 8: Good response	8 participants	72 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 12: No response	4 participants	11 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 12: Moderate response	3 participants	34 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 12: Good response	12 participants	83 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 16: No response	1 participants	9 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 16: Moderate response	4 participants	30 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 16: Good response	13 participants	86 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 20: No response	0 participants	9 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 20: Moderate response	5 participants	27 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 20: Good response	14 participants	85 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 24: No response	1 participants	7 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 24: Moderate response	2 participants	21 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 24: Good response	16 participants	89 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 28: No response	1 participants	5 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 28: Moderate response	0 participants	24 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 28: Good response	18 participants	86 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 32: No response	1 participants	3 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 32: Moderate response	2 participants	21 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 32: Good response	16 participants	91 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 36: No response	0 participants	4 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 36: Moderate response	3 participants	19 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 36: Good response	15 participants	91 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 40: No response	0 participants	2 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 40: Moderate response	1 participants	15 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 40: Good response	16 participants	94 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 44: No response	0 participants	5 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 44: Moderate response	2 participants	15 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 44: Good response	15 participants	87 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 48: No response	0 participants	4 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 48: Moderate response	2 participants	13 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 48: Good response	14 participants	90 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 52: No response	0 participants	5 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 52: Moderate response	3 participants	12 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Week 52: Good response	12 participants	90 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Early Withdrawal: No response	0 participants	11 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Early Withdrawal: Moderate response	1 participants	8 participants
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR Early Withdrawal: Good response	4 participants	9 participants

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

The SDAI is the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, patient and physician global assessment of disease activity assessed on 0-10 centimeter (cm) VAS (0 cm= no disease activity and 10 cm= worst disease activity), and CRP in milligrams per liter (mg/L). SDAI total score = 0-86. SDAI ≤3.3 indicates clinical remission, >3.3 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity.

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=136 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Baseline	31.23 units on a scale Standard Deviation 11.892	32.33 units on a scale Standard Deviation 11.620
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 2	-9.80 units on a scale Standard Deviation 10.406	-6.94 units on a scale Standard Deviation 9.710
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 4	-12.64 units on a scale Standard Deviation 10.502	-13.92 units on a scale Standard Deviation 10.666
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 8	-19.75 units on a scale Standard Deviation 12.978	-17.21 units on a scale Standard Deviation 12.900
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 12	-14.65 units on a scale Standard Deviation 15.003	-20.26 units on a scale Standard Deviation 12.739
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 16	-19.48 units on a scale Standard Deviation 9.649	-21.16 units on a scale Standard Deviation 11.945
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 20	-23.67 units on a scale Standard Deviation 14.015	-20.50 units on a scale Standard Deviation 11.630
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 24	-24.31 units on a scale Standard Deviation 13.469	-23.48 units on a scale Standard Deviation 12.417
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 28	-24.87 units on a scale Standard Deviation 12.554	-23.26 units on a scale Standard Deviation 12.418
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 32	-22.98 units on a scale Standard Deviation 12.850	-24.94 units on a scale Standard Deviation 11.399
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 36	-26.32 units on a scale Standard Deviation 12.795	-24.65 units on a scale Standard Deviation 11.268
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 40	-27.29 units on a scale Standard Deviation 13.280	-25.46 units on a scale Standard Deviation 12.210
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 44	-27.71 units on a scale Standard Deviation 12.851	-26.08 units on a scale Standard Deviation 11.835
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 48	-26.83 units on a scale Standard Deviation 13.615	-26.13 units on a scale Standard Deviation 11.189
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 52	-27.45 units on a scale Standard Deviation 14.351	-26.15 units on a scale Standard Deviation 12.791
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at early withdrawal	-18.94 units on a scale Standard Deviation 14.681	-9.45 units on a scale Standard Deviation 12.533

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

The CDAI is the numerical sum of four outcome parameters: TJC and SJC based on a 28-joint assessment, patient and physician's global assessment of disease activity assessed on 0-10 cm VAS (0 cm= no disease activity and 10 cm= worst disease activity). CDAI total score = 0-76. CDAI ≤2.8 indicates clinical remission, >2.8 to 10 = low disease activity, >10 to 22 = moderate disease activity, and >22 = high (or severe) disease activity.

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=139 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Baseline	29.69 units on a scale Standard Deviation 11.209	30.88 units on a scale Standard Deviation 10.953
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 2	-8.35 units on a scale Standard Deviation 10.433	-5.16 units on a scale Standard Deviation 9.323
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 4	-11.87 units on a scale Standard Deviation 10.062	-12.26 units on a scale Standard Deviation 10.137
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 8	-17.74 units on a scale Standard Deviation 12.289	-15.63 units on a scale Standard Deviation 11.873
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 12	-15.39 units on a scale Standard Deviation 14.216	-18.66 units on a scale Standard Deviation 11.895
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 16	-20.70 units on a scale Standard Deviation 11.694	-19.51 units on a scale Standard Deviation 11.124
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 20	-22.19 units on a scale Standard Deviation 13.545	-19.23 units on a scale Standard Deviation 11.433
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 24	-22.88 units on a scale Standard Deviation 12.720	-21.96 units on a scale Standard Deviation 11.825
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 28	-23.43 units on a scale Standard Deviation 11.573	-21.48 units on a scale Standard Deviation 11.585
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 32	-21.55 units on a scale Standard Deviation 12.019	-23.20 units on a scale Standard Deviation 10.842
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 36	-24.86 units on a scale Standard Deviation 11.854	-23.10 units on a scale Standard Deviation 11.263
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 40	-25.74 units on a scale Standard Deviation 12.488	-24.01 units on a scale Standard Deviation 11.282
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 44	-25.42 units on a scale Standard Deviation 11.971	-24.42 units on a scale Standard Deviation 11.186
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 48	-25.36 units on a scale Standard Deviation 12.718	-24.59 units on a scale Standard Deviation 10.645
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 52	-25.48 units on a scale Standard Deviation 13.049	-24.42 units on a scale Standard Deviation 12.599
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at early withdrawal	-17.78 units on a scale Standard Deviation 14.667	-8.68 units on a scale Standard Deviation 11.909

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 68. A reduction in number of tender joints compared to baseline indicates improvement. The outcome is reported as the percent change from baseline to end of treatment (52 weeks).

Outcome measures

Measure	Tocilizumab Monotherapy n=15 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=106 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Percent Change From Baseline in Total TJC on 68 Joints at Week 52	-83.12 percent change Standard Deviation 26.607	-80.44 percent change Standard Deviation 41.226

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

Number of tender joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 28. A reduction in number of tender joints compared to baseline indicates improvement.

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=139 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Baseline	10.4 tender joints Standard Deviation 6.46	12.9 tender joints Standard Deviation 7.06
Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 2	-3.4 tender joints Standard Deviation 5.62	-2.4 tender joints Standard Deviation 5.63
Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 4	-3.9 tender joints Standard Deviation 5.80	-5.4 tender joints Standard Deviation 6.14
Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 8	-6.6 tender joints Standard Deviation 6.41	-6.4 tender joints Standard Deviation 6.94
Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 12	-6.0 tender joints Standard Deviation 6.71	-8.0 tender joints Standard Deviation 7.35
Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 16	-7.9 tender joints Standard Deviation 6.35	-8.2 tender joints Standard Deviation 7.05
Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 20	-8.5 tender joints Standard Deviation 6.59	-8.3 tender joints Standard Deviation 7.09
Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 24	-8.3 tender joints Standard Deviation 7.41	-9.3 tender joints Standard Deviation 7.53
Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 28	-8.7 tender joints Standard Deviation 6.26	-9.2 tender joints Standard Deviation 7.04
Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 32	-7.6 tender joints Standard Deviation 6.64	-10.1 tender joints Standard Deviation 6.76
Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 36	-9.4 tender joints Standard Deviation 6.25	-9.7 tender joints Standard Deviation 7.23
Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 40	-10.1 tender joints Standard Deviation 6.64	-10.3 tender joints Standard Deviation 6.74
Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 44	-9.7 tender joints Standard Deviation 6.46	-10.4 tender joints Standard Deviation 6.63
Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 48	-9.6 tender joints Standard Deviation 6.36	-10.5 tender joints Standard Deviation 6.70
Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 52	-9.4 tender joints Standard Deviation 7.15	-10.4 tender joints Standard Deviation 8.01
Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at early withdrawal	-7.0 tender joints Standard Deviation 6.24	-3.3 tender joints Standard Deviation 7.46

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 66. A reduction in number of swollen joints compared to baseline indicates improvement. The outcome is reported as the percent change from baseline to end of treatment (52 weeks).

Outcome measures

Measure	Tocilizumab Monotherapy n=16 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=102 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Percent Change From Baseline in Total SJC on 66 Joints at Week 52	-89.31 percent change Standard Deviation 20.059	-74.77 percent change Standard Deviation 66.277

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.

Number of swollen joints was determined by examination of 28 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 28. A reduction in number of swollen joints compared to baseline indicates improvement.

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=139 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 32	-5.4 swollen joints Standard Deviation 5.10	-4.8 swollen joints Standard Deviation 4.37
Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 36	-6.5 swollen joints Standard Deviation 4.57	-4.9 swollen joints Standard Deviation 4.41
Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 40	-6.6 swollen joints Standard Deviation 5.12	-5.0 swollen joints Standard Deviation 4.82
Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 44	-6.6 swollen joints Standard Deviation 5.28	-5.2 swollen joints Standard Deviation 4.71
Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 48	-6.4 swollen joints Standard Deviation 4.83	-5.0 swollen joints Standard Deviation 4.48
Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 52	-6.3 swollen joints Standard Deviation 4.81	-5.1 swollen joints Standard Deviation 4.51
Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at early withdrawal	-5.8 swollen joints Standard Deviation 5.59	-1.7 swollen joints Standard Deviation 4.43
Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 24	-5.9 swollen joints Standard Deviation 5.12	-4.7 swollen joints Standard Deviation 4.21
Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 28	-6.4 swollen joints Standard Deviation 4.90	-4.4 swollen joints Standard Deviation 4.63
Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Baseline	7.0 swollen joints Standard Deviation 4.64	5.6 swollen joints Standard Deviation 4.43
Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 2	-2.5 swollen joints Standard Deviation 4.31	-0.8 swollen joints Standard Deviation 3.95
Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 4	-4.2 swollen joints Standard Deviation 3.79	-2.5 swollen joints Standard Deviation 3.81
Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 8	-4.8 swollen joints Standard Deviation 4.21	-3.2 swollen joints Standard Deviation 4.40
Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 12	-4.2 swollen joints Standard Deviation 4.37	-3.8 swollen joints Standard Deviation 4.36
Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 16	-5.3 swollen joints Standard Deviation 4.67	-3.9 swollen joints Standard Deviation 4.41
Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal Change at Week 20	-5.6 swollen joints Standard Deviation 5.08	-4.2 swollen joints Standard Deviation 4.60

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

Population: FAS population.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity.

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=140 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2 Baseline	0 participants	5 participants
Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2 Week 2	7 participants	18 participants
Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2 Week 4	9 participants	30 participants
Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2 Week 8	3 participants	25 participants
Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2 Week 12	6 participants	23 participants
Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2 Week 16	3 participants	20 participants
Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2 Week 20	3 participants	15 participants
Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2 Week 24	2 participants	15 participants
Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2 Week 28	4 participants	15 participants
Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2 Week 32	5 participants	14 participants
Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2 Week 36	1 participants	14 participants
Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2 Week 40	3 participants	14 participants
Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2 Week 44	5 participants	10 participants
Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2 Week 48	3 participants	12 participants
Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2 Week 52	0 participants	11 participants
Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2 Early withdrawal	2 participants	4 participants

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

Population: FAS population.

DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR <2.6 implied clinical remission.

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=140 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6 Week 20	11 participants	75 participants
Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6 Week 24	14 participants	76 participants
Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6 Baseline	0 participants	3 participants
Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6 Week 2	1 participants	15 participants
Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6 Week 4	2 participants	34 participants
Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6 Week 8	5 participants	53 participants
Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6 Week 12	6 participants	66 participants
Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6 Week 16	10 participants	72 participants
Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6 Week 28	14 participants	73 participants
Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6 Week 32	12 participants	80 participants
Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6 Week 36	14 participants	80 participants
Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6 Week 40	13 participants	81 participants
Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6 Week 44	10 participants	80 participants
Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6 Week 48	11 participants	78 participants
Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6 Week 52	12 participants	80 participants
Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6 Early withdrawal	3 participants	7 participants

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, at early withdrawal (up to Week 52), follow-up Week 4 (up to Week 56), and follow-up Week 8 (up to Week 60)

Population: FAS population.

Results are reported for number of participants who had non-biologic DMARD/corticosteroid dose reductions and/or discontinuation by reasons for dose reductions or discontinuation (safety reasons, discomfort, lack of efficacy, other reasons, and unknown reasons). Participants may be included under more than one reason.

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=140 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Baseline: Safety	0 participants	1 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Baseline: Discomfort	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Baseline: Lack of efficacy	0 participants	1 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Baseline: Other	0 participants	2 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Baseline: Unknown	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 2: Safety	0 participants	4 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 2: Discomfort	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 2: Lack of efficacy	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 2: Other	0 participants	7 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 2: Unknown	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 4: Safety	0 participants	6 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 4: Discomfort	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 4: Lack of efficacy	0 participants	1 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 4: Other	1 participants	9 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 4: Unknown	0 participants	1 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 8: Safety	0 participants	8 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 8: Discomfort	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 8: Lack of efficacy	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 8: Other	1 participants	13 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 8: Unknown	0 participants	1 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 12: Safety	0 participants	6 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 12: Discomfort 8	0 participants	2 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 12: Lack of efficacy	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 12: Other	2 participants	14 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 12: Unknown	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 16: Safety	0 participants	7 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 16: Discomfort	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 16: Lack of efficacy	0 participants	1 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 16: Other	2 participants	13 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 16: Unknown	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 20: Safety	0 participants	6 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 20: Discomfort	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 20: Lack of efficacy	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 20: Other	2 participants	9 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 20: Unknown	0 participants	1 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 24: Safety	0 participants	5 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 24:Discomfort	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 24: Lack of efficacy	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 24: Other	1 participants	13 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 24: Unknown	0 participants	1 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 28: Safety	0 participants	3 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 28: Discomfort	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 28: Lack of efficacy	0 participants	1 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 28: Other	1 participants	7 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 28: Unknown	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 32: Safety	0 participants	4 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 32: Discomfort	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 32: Lack of efficacy	0 participants	2 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 32: Other	1 participants	11 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 32: Unknown	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 36: Safety	0 participants	3 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 36: Discomfort	0 participants	1 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 36: Lack of efficacy	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 36: Other	2 participants	3 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 36: Unknown	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 40: Safety	0 participants	4 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 40: Discomfort	0 participants	1 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 40: Lack of efficacy	0 participants	1 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 40: Other	1 participants	1 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 40: Unknown	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 44: Safety	0 participants	3 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 44: Discomfort	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 44: Lack of efficacy	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 44: Other	0 participants	7 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 44: Unknown	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 48: Safety	0 participants	3 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 48: Discomfort	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 48: Lack of efficacy	0 participants	1 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 48: Other	1 participants	3 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 48: Unknown	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 52: Safety	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 52: Discomfort	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 52: Lack of efficacy	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 52: Other	0 participants	1 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Week 52: Unknown	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Early withdrawal: Safety	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Early withdrawal: Discomfort	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Early withdrawal: Lack of efficacy	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Early withdrawal: Other	1 participants	8 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Early withdrawal: Unknown	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Follow-up Week 4: Safety	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Follow-up Week 4: Discomfort	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Follow-up Week 4: Lack of efficacy	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Follow-up Week 4: Other	0 participants	2 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Follow-up Week 4: Unknown	0 participants	1 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Follow-up Week 8: Safety	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Follow-up Week 8: Discomfort	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Follow-up Week 8: Lack of efficacy	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Follow-up Week 8: Other	0 participants	0 participants
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation Follow-up Week 8: Unknown	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 52, and at early withdrawal (up to Week 52)

Population: FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome. Results are provided for single arm as participants in "Tocilizumab Monotherapy" arm did not receive methotrexate.

Methotrexate adherence was determined from responses to the question 'Over the last 3 months you were prescribed 12 doses of methotrexate, how many (approximately) have you taken?' Adherence (%) was calculated as: (Approximate number of doses taken/12)*100.

Outcome measures

Measure	Tocilizumab Monotherapy n=97 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Percentage of Methotrexate Adherence as Assessed by Methotrexate Adherence Questionnaire Baseline	96.82 percentage of methotrexate adherence Standard Deviation 7.747	—
Percentage of Methotrexate Adherence as Assessed by Methotrexate Adherence Questionnaire Week 12	92.92 percentage of methotrexate adherence Standard Deviation 14.412	—
Percentage of Methotrexate Adherence as Assessed by Methotrexate Adherence Questionnaire Week 24	91.54 percentage of methotrexate adherence Standard Deviation 20.915	—
Percentage of Methotrexate Adherence as Assessed by Methotrexate Adherence Questionnaire Week 36	90.14 percentage of methotrexate adherence Standard Deviation 21.456	—
Percentage of Methotrexate Adherence as Assessed by Methotrexate Adherence Questionnaire Week 52	95.28 percentage of methotrexate adherence Standard Deviation 11.417	—
Percentage of Methotrexate Adherence as Assessed by Methotrexate Adherence Questionnaire Early withdrawal	90.69 percentage of methotrexate adherence Standard Deviation 18.367	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

Population: FAS population.

Patient global assessment of disease activity was measured on a 0 to 100 mm horizontal VAS where 0 mm=no disease activity and 100 mm=maximum disease activity.

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=140 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Patient Global Assessment of Disease Activity VAS Score Baseline	59.6 mm Standard Deviation 26.94	62.3 mm Standard Deviation 20.72
Patient Global Assessment of Disease Activity VAS Score Week 2	50.3 mm Standard Deviation 24.01	54.5 mm Standard Deviation 22.12
Patient Global Assessment of Disease Activity VAS Score Week 4	46.4 mm Standard Deviation 26.43	42.3 mm Standard Deviation 23.22
Patient Global Assessment of Disease Activity VAS Score Week 8	35.8 mm Standard Deviation 24.73	36.2 mm Standard Deviation 24.43
Patient Global Assessment of Disease Activity VAS Score Week 12	41.3 mm Standard Deviation 27.67	32.1 mm Standard Deviation 23.91
Patient Global Assessment of Disease Activity VAS Score Week 16	29.6 mm Standard Deviation 21.59	29.2 mm Standard Deviation 22.55
Patient Global Assessment of Disease Activity VAS Score Week 20	25.7 mm Standard Deviation 23.77	29.9 mm Standard Deviation 22.99
Patient Global Assessment of Disease Activity VAS Score Week 24	23.8 mm Standard Deviation 19.55	26.6 mm Standard Deviation 21.92
Patient Global Assessment of Disease Activity VAS Score Week 28	23.2 mm Standard Deviation 16.47	26.7 mm Standard Deviation 23.12
Patient Global Assessment of Disease Activity VAS Score Week 32	24.0 mm Standard Deviation 17.81	24.3 mm Standard Deviation 21.66
Patient Global Assessment of Disease Activity VAS Score Week 36	24.1 mm Standard Deviation 19.13	22.3 mm Standard Deviation 21.86
Patient Global Assessment of Disease Activity VAS Score Week 40	22.5 mm Standard Deviation 19.31	21.4 mm Standard Deviation 20.81
Patient Global Assessment of Disease Activity VAS Score Week 44	22.7 mm Standard Deviation 20.62	22.0 mm Standard Deviation 22.83
Patient Global Assessment of Disease Activity VAS Score Week 48	22.9 mm Standard Deviation 23.31	18.9 mm Standard Deviation 20.57
Patient Global Assessment of Disease Activity VAS Score Week 52	20.6 mm Standard Deviation 18.96	21.4 mm Standard Deviation 23.07
Patient Global Assessment of Disease Activity VAS Score Early withdrawal	30.8 mm Standard Deviation 28.78	52.4 mm Standard Deviation 24.88

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

Population: FAS populations.

This assessment represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS where 0 mm= no pain to 100 mm= unbearable pain.

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=140 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Patient Pain VAS Score Week 28	24.8 mm Standard Deviation 19.15	25.6 mm Standard Deviation 23.18
Patient Pain VAS Score Baseline	50.5 mm Standard Deviation 23.78	57.5 mm Standard Deviation 21.06
Patient Pain VAS Score Week 2	46.1 mm Standard Deviation 22.43	51.1 mm Standard Deviation 22.58
Patient Pain VAS Score Week 4	47.0 mm Standard Deviation 26.69	42.4 mm Standard Deviation 23.80
Patient Pain VAS Score Week 8	37.8 mm Standard Deviation 25.75	35.3 mm Standard Deviation 24.30
Patient Pain VAS Score Week 12	40.9 mm Standard Deviation 29.56	30.8 mm Standard Deviation 23.29
Patient Pain VAS Score Week 16	29.7 mm Standard Deviation 20.83	26.8 mm Standard Deviation 22.61
Patient Pain VAS Score Week 20	27.6 mm Standard Deviation 25.48	28.6 mm Standard Deviation 23.74
Patient Pain VAS Score Week 24	29.9 mm Standard Deviation 22.76	25.2 mm Standard Deviation 22.16
Patient Pain VAS Score Week 32	25.1 mm Standard Deviation 17.92	22.6 mm Standard Deviation 21.30
Patient Pain VAS Score Week 36	29.6 mm Standard Deviation 20.03	22.1 mm Standard Deviation 21.68
Patient Pain VAS Score Week 40	27.6 mm Standard Deviation 22.70	20.9 mm Standard Deviation 21.24
Patient Pain VAS Score Week 44	26.7 mm Standard Deviation 24.25	20.0 mm Standard Deviation 21.26
Patient Pain VAS Score Week 48	28.6 mm Standard Deviation 28.98	17.6 mm Standard Deviation 19.66
Patient Pain VAS Score Week 52	22.4 mm Standard Deviation 19.70	19.0 mm Standard Deviation 19.83
Patient Pain VAS Score Early withdrawal	30.4 mm Standard Deviation 29.57	51.6 mm Standard Deviation 26.03

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

Population: FAS population.

The HAQ-DI questionnaire measures functional status (disability) and health-related quality of life. It measures the participant's ability to perform everyday tasks. The index consists of 20 questions regarding the function of the upper and lower extremities. These questions are summarized in 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common activities over past week. Each question is evaluated according to the degree of severity on a 4-point scale. Total score for HAQ-DI was the average of all questions and ranges from 0 = without any difficulty to 3 = unable to do.

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=140 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Baseline	1.806 units on a scale Standard Deviation 0.5551	1.738 units on a scale Standard Deviation 0.6406
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 2	1.558 units on a scale Standard Deviation 0.7319	1.659 units on a scale Standard Deviation 0.6210
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 4	1.616 units on a scale Standard Deviation 0.7720	1.546 units on a scale Standard Deviation 0.7351
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 8	1.508 units on a scale Standard Deviation 0.7597	1.404 units on a scale Standard Deviation 0.8115
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 12	1.488 units on a scale Standard Deviation 0.9304	1.333 units on a scale Standard Deviation 0.8272
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 16	1.351 units on a scale Standard Deviation 0.9586	1.312 units on a scale Standard Deviation 0.8621
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 20	1.409 units on a scale Standard Deviation 0.9071	1.318 units on a scale Standard Deviation 0.8608
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 24	1.330 units on a scale Standard Deviation 0.8379	1.261 units on a scale Standard Deviation 0.8915
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 28	1.330 units on a scale Standard Deviation 0.9412	1.221 units on a scale Standard Deviation 0.8730
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 32	1.351 units on a scale Standard Deviation 0.8816	1.232 units on a scale Standard Deviation 0.8870
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 36	1.432 units on a scale Standard Deviation 0.9048	1.170 units on a scale Standard Deviation 0.8757
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 40	1.479 units on a scale Standard Deviation 0.8975	1.199 units on a scale Standard Deviation 0.8908
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 44	1.442 units on a scale Standard Deviation 0.9392	1.130 units on a scale Standard Deviation 0.9206
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 48	1.361 units on a scale Standard Deviation 0.9685	1.114 units on a scale Standard Deviation 0.8815
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 52	1.338 units on a scale Standard Deviation 0.9796	1.154 units on a scale Standard Deviation 0.9187
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Early withdrawal	1.252 units on a scale Standard Deviation 1.1232	1.756 units on a scale Standard Deviation 0.7820

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

Population: FAS population.

The FACIT-F score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-F score for a total possible score of 0 (worse score) to 52 (better score).

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=140 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score Baseline	18.4 units on a scale Standard Deviation 11.14	24.3 units on a scale Standard Deviation 11.55
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score Week 2	23.1 units on a scale Standard Deviation 12.37	27.9 units on a scale Standard Deviation 11.03
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score Week 4	25.1 units on a scale Standard Deviation 12.28	30.7 units on a scale Standard Deviation 12.10
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score Week 8	30.2 units on a scale Standard Deviation 11.58	32.8 units on a scale Standard Deviation 11.91
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score Week 12	28.4 units on a scale Standard Deviation 11.71	33.7 units on a scale Standard Deviation 11.85
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score Week 16	31.3 units on a scale Standard Deviation 13.80	34.0 units on a scale Standard Deviation 12.53
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score Week 20	33.2 units on a scale Standard Deviation 13.57	34.1 units on a scale Standard Deviation 12.05
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score Week 24	33.8 units on a scale Standard Deviation 15.28	35.3 units on a scale Standard Deviation 10.98
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score Week 28	32.9 units on a scale Standard Deviation 12.06	35.5 units on a scale Standard Deviation 11.59
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score Week 32	34.1 units on a scale Standard Deviation 12.68	36.2 units on a scale Standard Deviation 11.32
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score Week 36	30.3 units on a scale Standard Deviation 13.62	36.8 units on a scale Standard Deviation 11.48
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score Week 40	31.7 units on a scale Standard Deviation 12.87	37.1 units on a scale Standard Deviation 11.69
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score Week 44	31.0 units on a scale Standard Deviation 14.02	37.2 units on a scale Standard Deviation 11.75
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score Week 48	31.6 units on a scale Standard Deviation 14.63	37.9 units on a scale Standard Deviation 11.73
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score Week 52	33.4 units on a scale Standard Deviation 14.17	38.1 units on a scale Standard Deviation 11.16
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score Early withdrawal	31.3 units on a scale Standard Deviation 2.63	24.5 units on a scale Standard Deviation 12.08

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

Population: FAS population.

A diary card was provided to participants to record home injections. Participants were asked to return all empty drug supply boxes, unused pre-filled syringe, and diary cards to the clinic at each visit as a measure of drug accountability and participant compliance. A participant was considered compliant if the participant correctly administered all scheduled doses of SC tocilizumab during the assessment period.

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=140 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records Baseline	21 participants	137 participants
Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records Week 2	20 participants	126 participants
Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records Week 4	20 participants	132 participants
Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records Week 8	18 participants	124 participants
Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records Week 12	18 participants	121 participants
Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records Week 16	19 participants	120 participants
Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records Week 20	18 participants	114 participants
Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records Week 24	16 participants	107 participants
Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records Week 28	19 participants	112 participants
Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records Week 32	17 participants	111 participants
Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records Week 36	17 participants	105 participants
Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records Week 40	16 participants	104 participants
Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records Week 44	16 participants	102 participants
Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records Week 48	13 participants	107 participants
Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records Week 52	16 participants	98 participants
Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records Early withdrawal	4 participants	27 participants

SECONDARY outcome

Timeframe: Baseline, Weeks 12 and 24, at early withdrawal (up to Week 52), and follow-up visit (8 weeks after last dose of tocilizumab, up to 60 weeks)

Population: FAS population.

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=140 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Number of Participants With Anti-Tocilizumab Antibodies Baseline	3 participants	6 participants
Number of Participants With Anti-Tocilizumab Antibodies Week 12	0 participants	—
Number of Participants With Anti-Tocilizumab Antibodies Week 24	0 participants	2 participants
Number of Participants With Anti-Tocilizumab Antibodies Early withdrawal	0 participants	0 participants
Number of Participants With Anti-Tocilizumab Antibodies Follow-up visit	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline, Weeks 12 and 24, at early withdrawal (up to Week 52), and follow-up visit (8 weeks after last dose of tocilizumab, up to 60 weeks)

Population: FAS population.

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=140 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Serum Levels of Tocilizumab Baseline	0.0000 micrograms per milliliter (mcg/mL) Standard Deviation 0.0000	0.0082 micrograms per milliliter (mcg/mL) Standard Deviation 0.09619
Serum Levels of Tocilizumab Week 12	35.3953 micrograms per milliliter (mcg/mL) Standard Deviation 22.69069	40.2529 micrograms per milliliter (mcg/mL) Standard Deviation 21.05801
Serum Levels of Tocilizumab Week 24	53.0416 micrograms per milliliter (mcg/mL) Standard Deviation 39.06367	43.9047 micrograms per milliliter (mcg/mL) Standard Deviation 30.41603
Serum Levels of Tocilizumab Early withdrawal	44.7160 micrograms per milliliter (mcg/mL) Standard Deviation 38.81521	17.6160 micrograms per milliliter (mcg/mL) Standard Deviation 22.92477
Serum Levels of Tocilizumab Follow-up visit	0.0597 micrograms per milliliter (mcg/mL) Standard Deviation 0.10335	2.3123 micrograms per milliliter (mcg/mL) Standard Deviation 7.40931

SECONDARY outcome

Timeframe: Baseline, Weeks 12 and 24, at early withdrawal (up to Week 52), and follow-up visit (8 weeks after last dose of tocilizumab, up to 60 weeks)

Population: FAS population.

Outcome measures

Measure	Tocilizumab Monotherapy n=21 Participants Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=140 Participants Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs) Baseline	43.63 nanograms per milliliter (ng/mL) Standard Deviation 10.947	42.40 nanograms per milliliter (ng/mL) Standard Deviation 12.087
Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs) Week 12	577.42 nanograms per milliliter (ng/mL) Standard Deviation 175.649	548.70 nanograms per milliliter (ng/mL) Standard Deviation 131.079
Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs) Week 24	602.25 nanograms per milliliter (ng/mL) Standard Deviation 158.541	521.07 nanograms per milliliter (ng/mL) Standard Deviation 160.464
Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs) Early withdrawal	639.75 nanograms per milliliter (ng/mL) Standard Deviation 99.644	327.95 nanograms per milliliter (ng/mL) Standard Deviation 229.481
Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs) Follow-up visit	132.23 nanograms per milliliter (ng/mL) Standard Deviation 93.048	125.07 nanograms per milliliter (ng/mL) Standard Deviation 211.038

Adverse Events

Tocilizumab Monotherapy

Serious events: 3 serious events

Other events: 19 other events

Deaths: 0 deaths

Tocilizumab in Combination With Methotrexate or Other DMARDs

Serious events: 7 serious events

Other events: 135 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tocilizumab Monotherapy n=21 participants at risk Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=140 participants at risk Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
Infections and infestations Arthritis bacterial	0.00% 0/21 • Baseline up to Week 60 FAS population	0.71% 1/140 • Baseline up to Week 60 FAS population
Infections and infestations Cellulitis	0.00% 0/21 • Baseline up to Week 60 FAS population	0.71% 1/140 • Baseline up to Week 60 FAS population
Infections and infestations Pneumonia	4.8% 1/21 • Baseline up to Week 60 FAS population	0.00% 0/140 • Baseline up to Week 60 FAS population
Infections and infestations Sinusitis	4.8% 1/21 • Baseline up to Week 60 FAS population	0.00% 0/140 • Baseline up to Week 60 FAS population
Infections and infestations Subcutaneous abscess	0.00% 0/21 • Baseline up to Week 60 FAS population	0.71% 1/140 • Baseline up to Week 60 FAS population
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/21 • Baseline up to Week 60 FAS population	0.71% 1/140 • Baseline up to Week 60 FAS population
Injury, poisoning and procedural complications Wound	4.8% 1/21 • Baseline up to Week 60 FAS population	0.00% 0/140 • Baseline up to Week 60 FAS population
Cardiac disorders Atrial fibrillation	0.00% 0/21 • Baseline up to Week 60 FAS population	0.71% 1/140 • Baseline up to Week 60 FAS population
Gastrointestinal disorders Vomiting	4.8% 1/21 • Baseline up to Week 60 FAS population	0.00% 0/140 • Baseline up to Week 60 FAS population
Musculoskeletal and connective tissue disorders Costochondritis	0.00% 0/21 • Baseline up to Week 60 FAS population	0.71% 1/140 • Baseline up to Week 60 FAS population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	4.8% 1/21 • Baseline up to Week 60 FAS population	0.00% 0/140 • Baseline up to Week 60 FAS population
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.00% 0/21 • Baseline up to Week 60 FAS population	0.71% 1/140 • Baseline up to Week 60 FAS population
Skin and subcutaneous tissue disorders Drug eruption	0.00% 0/21 • Baseline up to Week 60 FAS population	0.71% 1/140 • Baseline up to Week 60 FAS population
Surgical and medical procedures Knee arthroplasty	4.8% 1/21 • Baseline up to Week 60 FAS population	0.00% 0/140 • Baseline up to Week 60 FAS population

Other adverse events

Measure	Tocilizumab Monotherapy n=21 participants at risk Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.	Tocilizumab in Combination With Methotrexate or Other DMARDs n=140 participants at risk Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
General disorders Fatigue	4.8% 1/21 • Baseline up to Week 60 FAS population	8.6% 12/140 • Baseline up to Week 60 FAS population
General disorders Injection site erythema	4.8% 1/21 • Baseline up to Week 60 FAS population	7.9% 11/140 • Baseline up to Week 60 FAS population
General disorders Influenza like illness	4.8% 1/21 • Baseline up to Week 60 FAS population	5.7% 8/140 • Baseline up to Week 60 FAS population
General disorders Peripheral swelling	4.8% 1/21 • Baseline up to Week 60 FAS population	5.7% 8/140 • Baseline up to Week 60 FAS population
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	14.3% 3/21 • Baseline up to Week 60 FAS population	19.3% 27/140 • Baseline up to Week 60 FAS population
Respiratory, thoracic and mediastinal disorders Cough	19.0% 4/21 • Baseline up to Week 60 FAS population	15.0% 21/140 • Baseline up to Week 60 FAS population
Respiratory, thoracic and mediastinal disorders Productive cough	9.5% 2/21 • Baseline up to Week 60 FAS population	2.1% 3/140 • Baseline up to Week 60 FAS population
Skin and subcutaneous tissue disorders Rash	0.00% 0/21 • Baseline up to Week 60 FAS population	12.9% 18/140 • Baseline up to Week 60 FAS population
Injury, poisoning and procedural complications Contusion	9.5% 2/21 • Baseline up to Week 60 FAS population	9.3% 13/140 • Baseline up to Week 60 FAS population
Injury, poisoning and procedural complications Fall	4.8% 1/21 • Baseline up to Week 60 FAS population	10.0% 14/140 • Baseline up to Week 60 FAS population
Injury, poisoning and procedural complications Laceration	0.00% 0/21 • Baseline up to Week 60 FAS population	5.0% 7/140 • Baseline up to Week 60 FAS population
Nervous system disorders Headache	19.0% 4/21 • Baseline up to Week 60 FAS population	9.3% 13/140 • Baseline up to Week 60 FAS population
Nervous system disorders Dizziness	9.5% 2/21 • Baseline up to Week 60 FAS population	5.7% 8/140 • Baseline up to Week 60 FAS population
Nervous system disorders Migraine	4.8% 1/21 • Baseline up to Week 60 FAS population	5.0% 7/140 • Baseline up to Week 60 FAS population
Nervous system disorders Paraesthesia	9.5% 2/21 • Baseline up to Week 60 FAS population	4.3% 6/140 • Baseline up to Week 60 FAS population
Nervous system disorders Lethargy	0.00% 0/21 • Baseline up to Week 60 FAS population	5.0% 7/140 • Baseline up to Week 60 FAS population
Blood and lymphatic system disorders Neutropenia	0.00% 0/21 • Baseline up to Week 60 FAS population	10.0% 14/140 • Baseline up to Week 60 FAS population
Investigations Neutrophil count decreased	0.00% 0/21 • Baseline up to Week 60 FAS population	9.3% 13/140 • Baseline up to Week 60 FAS population
Investigations Blood cholesterol increased	14.3% 3/21 • Baseline up to Week 60 FAS population	3.6% 5/140 • Baseline up to Week 60 FAS population
Musculoskeletal and connective tissue disorders Arthralgia	4.8% 1/21 • Baseline up to Week 60 FAS population	8.6% 12/140 • Baseline up to Week 60 FAS population
Musculoskeletal and connective tissue disorders Back pain	14.3% 3/21 • Baseline up to Week 60 FAS population	7.1% 10/140 • Baseline up to Week 60 FAS population
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/21 • Baseline up to Week 60 FAS population	7.9% 11/140 • Baseline up to Week 60 FAS population
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.00% 0/21 • Baseline up to Week 60 FAS population	7.9% 11/140 • Baseline up to Week 60 FAS population
Infections and infestations Nasopharyngitis	23.8% 5/21 • Baseline up to Week 60 FAS population	23.6% 33/140 • Baseline up to Week 60 FAS population
Infections and infestations Lower respiratory tract infection	28.6% 6/21 • Baseline up to Week 60 FAS population	17.9% 25/140 • Baseline up to Week 60 FAS population
Infections and infestations Upper respiratory tract infection	9.5% 2/21 • Baseline up to Week 60 FAS population	14.3% 20/140 • Baseline up to Week 60 FAS population
Infections and infestations Urinary tract infection	23.8% 5/21 • Baseline up to Week 60 FAS population	11.4% 16/140 • Baseline up to Week 60 FAS population
Infections and infestations Oral herpes	4.8% 1/21 • Baseline up to Week 60 FAS population	7.1% 10/140 • Baseline up to Week 60 FAS population
Infections and infestations Lower respiratory tract infection viral	9.5% 2/21 • Baseline up to Week 60 FAS population	0.00% 0/140 • Baseline up to Week 60 FAS population
Gastrointestinal disorders Diarrhoea	9.5% 2/21 • Baseline up to Week 60 FAS population	22.9% 32/140 • Baseline up to Week 60 FAS population
Gastrointestinal disorders Nausea	0.00% 0/21 • Baseline up to Week 60 FAS population	15.0% 21/140 • Baseline up to Week 60 FAS population
Gastrointestinal disorders Mouth ulceration	4.8% 1/21 • Baseline up to Week 60 FAS population	12.9% 18/140 • Baseline up to Week 60 FAS population
Gastrointestinal disorders Vomiting	9.5% 2/21 • Baseline up to Week 60 FAS population	11.4% 16/140 • Baseline up to Week 60 FAS population
Gastrointestinal disorders Abdominal pain	0.00% 0/21 • Baseline up to Week 60 FAS population	5.0% 7/140 • Baseline up to Week 60 FAS population
Investigations Alanine aminotransferase increased	9.5% 2/21 • Baseline up to Week 60 FAS population	22.1% 31/140 • Baseline up to Week 60 FAS population
General disorders Injection site bruising	14.3% 3/21 • Baseline up to Week 60 FAS population	8.6% 12/140 • Baseline up to Week 60 FAS population

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but 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