Trial Outcomes & Findings for TOSCARA Study: A Study of Subcutaneous Tocilizumab (RoActemra/Actemra) in Participants With Active Rheumatoid Arthritis Naïve to RoActemra/Actemra Treatment (NCT NCT02031471)

NCT ID: NCT02031471

Last Updated: 2017-08-01

Results Overview

The DAS28 score is a measure of the participant's disease activity calculated using the tender joint count of 28 joints (TJC28), swollen joint count of 28 joints (SJC28), patient's global assessment of disease activity visual analog scale (PGA VAS) with 0=no disease activity to 100=maximum disease activity displayed on the 100-millimeter (mm) horizontal VAS and acute phase reactant (erythrocyte sedimentation rate \[ESR\] or C-reactive protein \[CRP\]) for a total possible score of 0 to 10. For this study ESR was used to calculate the DAS28 score. The index is calculated using the following formula: DAS28 = (0.56\*√\[TJC28\]) + (0.28\*√\[SJC28\]) + (0.70\*ln\[ESR\]) + (0.014\*VAS). Higher scores represent higher disease activity. A negative change from baseline indicates an improvement.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 57 participants
• Primary outcome timeframe: From baseline to Week 24
• Results posted on: 2017-08-01

Participant Flow

A total of 62 participants were screened, 57 participants were enrolled. Participants who completed the 24 Week Treatment Period achieving at least a moderate European League Against Rheumatism (EULAR) response at Week 24 were allowed to enter the Long Term Extension (LTE) Period.

Participant milestones

Measure	Tocilizumab Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the long term extension (LTE) period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. Participants entered 8 weeks of follow-up either at the end of the 24-week open-label core study or after completion of the LTE. A fixed dose of 162 milligram (mg) tocilizumab was administered subcutaneously once weekly.
24 Week Treatment Period STARTED	57
24 Week Treatment Period COMPLETED	46
24 Week Treatment Period NOT COMPLETED	11
Long Term Extension (LTE) Period STARTED	39
Long Term Extension (LTE) Period COMPLETED	37
Long Term Extension (LTE) Period NOT COMPLETED	2

Reasons for withdrawal

Measure	Tocilizumab Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the long term extension (LTE) period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. Participants entered 8 weeks of follow-up either at the end of the 24-week open-label core study or after completion of the LTE. A fixed dose of 162 milligram (mg) tocilizumab was administered subcutaneously once weekly.
24 Week Treatment Period Adverse Event	6
24 Week Treatment Period Participant Decision to Withdraw	2
24 Week Treatment Period Protocol Violation	1
24 Week Treatment Period Insufficient Therapeutic Response	1
24 Week Treatment Period Hypersensitivity Reaction	1
Long Term Extension (LTE) Period Adverse Event	1
Long Term Extension (LTE) Period Insufficient Therapeutic Response	1

Baseline Characteristics

TOSCARA Study: A Study of Subcutaneous Tocilizumab (RoActemra/Actemra) in Participants With Active Rheumatoid Arthritis Naïve to RoActemra/Actemra Treatment

Baseline characteristics by cohort

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Age, Continuous	54.49 years STANDARD_DEVIATION 11.08 • n=5 Participants
Sex: Female, Male Female	44 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline to Week 24

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

The DAS28 score is a measure of the participant's disease activity calculated using the tender joint count of 28 joints (TJC28), swollen joint count of 28 joints (SJC28), patient's global assessment of disease activity visual analog scale (PGA VAS) with 0=no disease activity to 100=maximum disease activity displayed on the 100-millimeter (mm) horizontal VAS and acute phase reactant (erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP]) for a total possible score of 0 to 10. For this study ESR was used to calculate the DAS28 score. The index is calculated using the following formula: DAS28 = (0.56*√[TJC28]) + (0.28*√[SJC28]) + (0.70*ln[ESR]) + (0.014*VAS). Higher scores represent higher disease activity. A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score in the Full Analysis Set (FAS) Baseline (n=56)	5.55 Units on a scale Standard Deviation 1.17
Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score in the Full Analysis Set (FAS) Change at Week 24 (n=42)	-3.24 Units on a scale Standard Deviation 1.47

PRIMARY outcome

Timeframe: From baseline to Week 24

Population: The PPS consisted of all participants of the FAS having a value at baseline and at Week 24 for the endpoint DAS28-ESR, excluding sponsor defined deviation(s) which could have affected the evaluation of the primary endpoint (DAS28-ESR). Here, n is the number of participants with evaluable data for this outcome measure.

The DAS28 score is a measure of the participant's disease activity calculated using the TJC28, SJC28, PGA VAS with 0=no disease activity to 100=maximum disease activity displayed on the 100-mm horizontal VAS and acute phase reactant (ESR or CRP) for a total possible score of 0 to 10. For this study ESR was used to calculate the DAS28 score. The index is calculated using the following formula: DAS28 = (0.56*√[TJC28]) + (0.28*√[SJC28]) + (0.70*ln[ESR]) + (0.014*VAS). Higher scores represent higher disease activity. A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score in the Per Protocol Set (PPS) Baseline (n= 27)	5.73 Units on a scale Standard Deviation 1.33
Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score in the Per Protocol Set (PPS) Change at Week 24 (n= 20)	-3.21 Units on a scale Standard Deviation 1.42

SECONDARY outcome

Timeframe: From Baseline to Week 2, Week 24, and Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of participants with evaluable data for this outcome measure.

The ACR core set of outcome measures and their definition of improvement includes a >= 20% improvement (ACR20) compared to Baseline in both SJC and TJC as well as in three out of five additional parameters: Physician's Global Assessment of disease activity VAS, PGA VAS, patient's assessment of pain VAS, Health Assessment Questionnaire-Disability Index (HAQ-DI), and acute phase reactant (CRP or ESR). VAS range for all assessments was 0=no disease activity to 100=maximum disease activity displayed on the 100-mm horizontal VAS. Achievement of an ACR50 requires a >= 50% improvement in the same parameters and an ACR70 requires a >= 70% improvement.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Percentage of Participants With Positive American College of Rheumatology (ACR) Response Scores Baseline: ACR 20 (n=55)	0 percentage of participants
Percentage of Participants With Positive American College of Rheumatology (ACR) Response Scores Week 2: ACR 20 (n=51)	21.6 percentage of participants
Percentage of Participants With Positive American College of Rheumatology (ACR) Response Scores Week 24: ACR 20 (n=39)	84.6 percentage of participants
Percentage of Participants With Positive American College of Rheumatology (ACR) Response Scores Week 52: ACR 20 (n=8)	100 percentage of participants
Percentage of Participants With Positive American College of Rheumatology (ACR) Response Scores Baseline: ACR 50 (n=55)	0 percentage of participants
Percentage of Participants With Positive American College of Rheumatology (ACR) Response Scores Week 2: ACR 50 (n=52)	1.9 percentage of participants
Percentage of Participants With Positive American College of Rheumatology (ACR) Response Scores Week 24: ACR 50 (n=39)	66.7 percentage of participants
Percentage of Participants With Positive American College of Rheumatology (ACR) Response Scores Week 52: ACR 50 (n=8)	62.5 percentage of participants
Percentage of Participants With Positive American College of Rheumatology (ACR) Response Scores Baseline: ACR 70 (n=55)	0 percentage of participants
Percentage of Participants With Positive American College of Rheumatology (ACR) Response Scores Week 2: ACR 70 (n=52)	0 percentage of participants
Percentage of Participants With Positive American College of Rheumatology (ACR) Response Scores Week 24: ACR 70 (n=39)	38.5 percentage of participants
Percentage of Participants With Positive American College of Rheumatology (ACR) Response Scores Week 52: ACR 70 (n=8)	25.0 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to Week 2, Week 24

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

EULAR response was calculated as the difference between DAS28-ESR scores at baseline and Week 24, and reported as the percentage of participants with good, moderate, or no response. Good responders = decrease from baseline >1.2 with a DAS28 score of <=3.2; moderate responders = decrease from baseline >1.2 with a DAS28 score of >3.2, or decrease from baseline >0.6 to <=1.2 with a DAS28 score of <=5.1; non-responders = decrease from baseline <=0.6 or decrease from baseline >0.6 and <=1.2 with a DAS28 score of >5.1.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Percentage of Participants With Responses According to European League Against Rheumatism (EULAR ) Criteria Week 2: Good response (n=56)	17.9 percentage of participants
Percentage of Participants With Responses According to European League Against Rheumatism (EULAR ) Criteria Week 24: Good response (n=42)	76.2 percentage of participants
Percentage of Participants With Responses According to European League Against Rheumatism (EULAR ) Criteria Week 2: Moderate response (n=56)	50.0 percentage of participants
Percentage of Participants With Responses According to European League Against Rheumatism (EULAR ) Criteria Week 24: Moderate response (n=42)	19.0 percentage of participants
Percentage of Participants With Responses According to European League Against Rheumatism (EULAR ) Criteria Week 2: No response (n=56)	32.1 percentage of participants
Percentage of Participants With Responses According to European League Against Rheumatism (EULAR ) Criteria Week 24: No response (n=42)	4.8 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to Week 2, Week 24 and Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

SDAI is a similar index to DAS28 but has the advantage of not needing a complicated mathematical formula for its determination, but a simple arithmetical addition of TJC28 and SJC28, PGA VAS and Physician Global Assessment of disease activity VAS, and CRP concentration in mg/L. CDAI does not incorporate an acute response, therefore it can be used to evaluate disease activity in the absence of laboratory testing of CRP and ESR. VAS range for all assessments was 0=no disease activity to 100=maximum disease activity displayed on the 100-mm horizontal VAS. SDAI scores ranged from 0 to 86, CDAI from 0 to 76 with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Change From Baseline in Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI) Baseline (n=53)	33.26 Units on a scale Standard Deviation 13.50
Change From Baseline in Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI) Change at Week 2: SDAI (n=52)	-9.00 Units on a scale Standard Deviation 11.89
Change From Baseline in Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI) Change at Week 24: SDAI (n=38)	-25.33 Units on a scale Standard Deviation 13.63
Change From Baseline in Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI) Change at Week 52: SDAI (n=7)	-34.04 Units on a scale Standard Deviation 16.01
Change From Baseline in Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI) Baseline: CDAI (n= 55)	31.86 Units on a scale Standard Deviation 12.60
Change From Baseline in Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI) Change at Week 2: CDAI (n=55)	-7.61 Units on a scale Standard Deviation 11.51
Change From Baseline in Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI) Change at Week 24: CDAI (n=42)	-23.55 Units on a scale Standard Deviation 13.03
Change From Baseline in Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI) Change at Week 52: CDAI (n=8)	-29.99 Units on a scale Standard Deviation 13.89

SECONDARY outcome

Timeframe: From Baseline to Week 2, Week 24 and Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of participants with evaluable data for this outcome measure

An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as swollen/not swollen and tender/not tender by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints were not taken into consideration for swelling or tenderness. A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Change in Total Tender/Swollen Joint Counts (TJC/SJC) Baseline: TJC (n=53)	16.02 Joint Counts Standard Deviation 11.77
Change in Total Tender/Swollen Joint Counts (TJC/SJC) Change at Week 2: TJC (n=53)	-3.58 Joint Counts Standard Deviation 8.91
Change in Total Tender/Swollen Joint Counts (TJC/SJC) Change at Week 24: TJC (n=41)	-12.10 Joint Counts Standard Deviation 11.07
Change in Total Tender/Swollen Joint Counts (TJC/SJC) Change at Week 52: TJC (n=8)	-17.25 Joint Counts Standard Deviation 13.02
Change in Total Tender/Swollen Joint Counts (TJC/SJC) Baseline: SJC (n=55)	10.20 Joint Counts Standard Deviation 7.14
Change in Total Tender/Swollen Joint Counts (TJC/SJC) Change at Week 2: SJC (n=55)	-3.93 Joint Counts Standard Deviation 7.33
Change in Total Tender/Swollen Joint Counts (TJC/SJC) Change at Week 24: SJC (n=42)	-9.81 Joint Counts Standard Deviation 7.84
Change in Total Tender/Swollen Joint Counts (TJC/SJC) Change at Week 52: SJC (n=8)	-11.75 Joint Counts Standard Deviation 7.76

SECONDARY outcome

Timeframe: Up to Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here, number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Outcome measures

Measure

Tocilizumab n=26 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.

Percentage of Participants With Corticosteroid Dose Reduction/Discontinuation

50.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 2, Week 24 and Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of participants with evaluable data for this outcome measure.

CDAI is calculated by simple arithmetical addition of TJC28 and SJC28, PGA VAS and Physician Global Assessment of disease activity VAS. VAS range was 0=no disease activity to 100=maximum disease activity displayed on the 100-mm horizontal VAS. Total CDAI score ranges from 0 to 76 with higher scores indicating increased disease activity. Clinical remission = score ≤ 2.8; Low disease activity = score > 2.8 and ≤ 10.0; Moderate disease activity = score > 10.0 and ≤ 22.0; High disease activity = score > 22.0.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity Baseline: Clinical remission (n=55)	0 percentage of participants
Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity Week 2: Clinical remission (n=56)	1.8 percentage of participants
Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity Week 24: Clinical remission (n=43)	30.2 percentage of participants
Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity Week 52: Clinical remission (n=8)	37.5 percentage of participants
Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity Baseline: Low disease activity (n=55)	0 percentage of participants
Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity Week 2: Low disease activity (n=56)	7.1 percentage of participants
Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity Week 24: Low disease activity (n=43)	34.9 percentage of participants
Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity Week 52: Low disease activity (n=8)	25.0 percentage of participants
Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity Baseline: Moderate disease activity (n=55)	21.8 percentage of participants
Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity Week 2: Moderate disease activity (n=56)	48.2 percentage of participants
Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity Week 24: Moderate disease activity (n=43)	30.2 percentage of participants
Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity Week 52: Moderate disease activity (n=8)	37.5 percentage of participants
Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity Baseline: High disease activity (n=55)	78.2 percentage of participants
Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity Week 2: High disease activity (n=56)	42.9 percentage of participants
Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity Week 24: High disease activity (n=43)	4.7 percentage of participants
Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity Week 52: High disease activity (n=8)	0 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to Week 2, Week 24 and Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of participants with evaluable data for this outcome measure.

SDAI is calculated by simple arithmetical addition of TJC28 and SJC28, PGA VAS and Physician Global Assessment of disease activity VAS, and CRP concentration in mg/L. VAS range was 0=no disease activity to 100=maximum disease activity displayed on the 100-mm horizontal VAS. Total SDAI score ranges from 0 to 86 with higher scores indicating increased disease activity. Clinical remission = score ≤ 3.3; Low disease activity = score > 3.3 and ≤ 11.0; Moderate disease activity = score > 11.0 and ≤ 26.0; high disease activity = score > 26.0.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity Week 24: High disease activity (n=40)	5.0 percentage of participants
Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity Baseline: Clinical remission (n=53)	0 percentage of participants
Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity Week 2: Clinical remission (n=55)	1.8 percentage of participants
Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity Week 24: Clinical remission (n=40)	30.0 percentage of participants
Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity Week 52: Clinical remission (n=7)	42.9 percentage of participants
Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity Baseline: Low disease activity (n=53)	0 percentage of participants
Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity Week 2: Low disease activity (n=55)	7.3 percentage of participants
Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity Week 24: Low disease activity (n=40)	40.0 percentage of participants
Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity Week 52: Low disease activity (n=7)	14.3 percentage of participants
Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity Baseline: Moderate disease activity (n=53)	30.2 percentage of participants
Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity Week 2: Moderate disease activity (n=55)	54.5 percentage of participants
Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity Week 24: Moderate disease activity (n=40)	25.0 percentage of participants
Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity Week 52: Moderate disease activity (n=7)	42.9 percentage of participants
Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity Baseline: High disease activity (n=53)	69.8 percentage of participants
Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity Week 2: High disease activity (n=55)	36.4 percentage of participants
Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity Week 52: High disease activity (n=7)	0 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to Week 2, Week 24 and Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of participants with evaluable data for this outcome measure.

The DAS28 score is a measure of the participant's disease activity calculated using TJC28, SJC28, PGA VAS with 0=no disease activity to 100=maximum disease activity displayed on the 100-millimeter (mm) horizontal VAS and acute phase reactant (erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP]) for a total possible score of 0 to 10. For this study ESR was used to calculate the DAS28 score. The index is calculated using the following formula: DAS28 = (0.56*√[TJC28]) + (0.28*√[SJC28]) + (0.70*ln[ESR]) + (0.014*VAS). Higher scores represent higher disease activity. Clinical remission = score <2.6; Low disease activity = score ≥2.6 and ≤3.2; Moderate disease activity = score > 3.2 and ≤5.1; High disease activity = score >5.1.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity Baseline: Clinical remission (n=56)	0 percentage of participants
Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity Week 2: Clinical remission (n=56)	7.1 percentage of participants
Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity Week 24: Clinical remission (n=42)	64.3 percentage of participants
Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity Week 52: Clinical remission (n=8)	87.5 percentage of participants
Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity Baseline: Low disease activity (n=56)	1.8 percentage of participants
Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity Week 2: Low disease activity (n=56)	16.1 percentage of participants
Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity Week 24: Low disease activity (n=42)	16.7 percentage of participants
Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity Week 52: Low disease activity (n=8)	0 percentage of participants
Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity Baseline: Moderate disease activity (n=56)	35.7 percentage of participants
Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity Week 2: Moderate disease activity (n=56)	53.6 percentage of participants
Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity Week 24: Moderate disease activity (n=42)	19.0 percentage of participants
Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity Week 52: Moderate disease activity (n=8)	12.5 percentage of participants
Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity Baseline: High disease activity (n=56)	62.5 percentage of participants
Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity Week 2: High disease activity (n=56)	23.2 percentage of participants
Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity Week 24: High disease activity (n=42)	0 percentage of participants
Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity Week 52: High disease activity (n=8)	0 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to Week 2, Week 24 and Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of participants with evaluable data for this outcome measure.

The DAS28 score is a measure of the participant's disease activity calculated using TJC28, SJC28, PGA VAS with 0=no disease activity to 100=maximum disease activity displayed on the 100-millimeter (mm) horizontal VAS and acute phase reactant (erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP]) for a total possible score of 0 to 10. For this study ESR was used to calculate the DAS28 score. The index is calculated using the following formula: DAS28 = (0.56*√[TJC28]) + (0.28*√[SJC28]) + (0.70*ln[ESR]) + (0.014*VAS). Higher scores represent higher disease activity. DAS28 Clinically Significant Improvement was defined as a DAS28 score reduction of at least 1.2 units from Baseline.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Percentage of Participants Achieving a Clinically Significant Improvement in DAS28 Week 2 (n=56)	66.1 percentage of participants
Percentage of Participants Achieving a Clinically Significant Improvement in DAS28 Week 24 (n=42)	90.5 percentage of participants
Percentage of Participants Achieving a Clinically Significant Improvement in DAS28 Week 52 (n=8)	100 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to Week 2, Week 24 and Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Physician's Global Assessment of disease activity VAS represents the physician's assessment of the participant's current disease activity on a 100 mm horizontal VAS. The extreme left end of the line represents 0= "no disease activity" (symptom-free and no arthritis symptoms) and the extreme right end 100= "maximum disease activity". This was completed by the Treating Physician (or designee). A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Change From Baseline in Physician's Global Assessment of Disease Activity VAS Baseline (n=56)	64.93 Units on a scale Standard Deviation 17.73
Change From Baseline in Physician's Global Assessment of Disease Activity VAS Change at Week 2 (n=56)	-16.34 Units on a scale Standard Deviation 16.88
Change From Baseline in Physician's Global Assessment of Disease Activity VAS Change at Week 24 (n=45)	-48.93 Units on a scale Standard Deviation 25.06
Change From Baseline in Physician's Global Assessment of Disease Activity VAS Change at Week 52 (n=9)	-57.44 Units on a scale Standard Deviation 23.26

SECONDARY outcome

Timeframe: From Baseline to Week 2, Week 24 and Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

PGA VAS represents the participant's overall assessment of their current disease activity on a 100 mm horizontal VAS. The extreme left end of the line represents 0= "no disease activity" (symptom-free and no arthritis symptoms) and the extreme right end 100="maximum disease activity" (maximum arthritis disease activity). A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Change From Baseline in Patient's Global Assessment of Disease Activity VAS Change at Week 24 (n=46)	-36.02 Units on a scale Standard Deviation 29.38
Change From Baseline in Patient's Global Assessment of Disease Activity VAS Baseline (n=57)	67.28 Units on a scale Standard Deviation 22.25
Change From Baseline in Patient's Global Assessment of Disease Activity VAS Change at Week 2 (n=57)	-11.82 Units on a scale Standard Deviation 23.23
Change From Baseline in Patient's Global Assessment of Disease Activity VAS Change at Week 52 (n=9)	-44.78 Units on a scale Standard Deviation 35.87

SECONDARY outcome

Timeframe: From Baseline to Week 2 and Week 24

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

Patient's Assessment of Pain VAS represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS. The extreme left end of the line represents 0="no pain" and the extreme right end 100="unbearable pain". A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Change From Baseline in Patient's Assessment of Pain VAS Baseline (n=57)	66.77 Units on a scale Standard Deviation 21.43
Change From Baseline in Patient's Assessment of Pain VAS Change at Week 2 (n=57)	-11.32 Units on a scale Standard Deviation 19.74
Change From Baseline in Patient's Assessment of Pain VAS Change at Week 24 (n=46)	-35.37 Units on a scale Standard Deviation 27.03
Change From Baseline in Patient's Assessment of Pain VAS Change at Week 52 (n=9)	-49.33 Units on a scale Standard Deviation 39.58

SECONDARY outcome

Timeframe: From Baseline to Week 2, Week 24 and Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

A negative change from baseline in CRP level indicates an improvement.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Acute Phase Reactants: Change From Baseline in CRP Baseline (n=55)	13.79 milligrams per liter (mg/L) Standard Deviation 20.78
Acute Phase Reactants: Change From Baseline in CRP Change at Week 2 (n=54)	-13.19 milligrams per liter (mg/L) Standard Deviation 20.64
Acute Phase Reactants: Change From Baseline in CRP Change at Week 24 (n=42)	-10.12 milligrams per liter (mg/L) Standard Deviation 14.50
Acute Phase Reactants: Change From Baseline in CRP Change at Week 52 (n=8)	-25.07 milligrams per liter (mg/L) Standard Deviation 23.03

SECONDARY outcome

Timeframe: From Baseline to Week 2, Week 24 and Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

A negative change from baseline in ESR indicates an improvement.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Acute Phase Reactants: Change From Baseline in ESR Baseline (n=56)	33.75 millimeters per hour (mm/hr) Standard Deviation 28.90
Acute Phase Reactants: Change From Baseline in ESR Change at Week 2 (n=55)	-19.95 millimeters per hour (mm/hr) Standard Deviation 18.22
Acute Phase Reactants: Change From Baseline in ESR Change at Week 24 (n=44)	-22.80 millimeters per hour (mm/hr) Standard Deviation 24.88
Acute Phase Reactants: Change From Baseline in ESR Change at Week 52 (n=9)	-27.78 millimeters per hour (mm/hr) Standard Deviation 23.82

SECONDARY outcome

Timeframe: From Baseline to Week 2, Week 24 and Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

The Stanford HAQ-DI is a patient-oriented outcome assessment questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities. Each category contains multiple questions, which were answered using a 4-point scale from 0 to 3. The overall index score was an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Baseline (n=57)	1.44 Units on a scale Standard Deviation 0.68
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Change at Week 2 (n=57)	-0.08 Units on a scale Standard Deviation 0.43
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Change at Week 24 (n=46)	-0.54 Units on a scale Standard Deviation 0.68
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Change at Week 52 (n=9)	-1.33 Units on a scale Standard Deviation 0.68

SECONDARY outcome

Timeframe: From Baseline to Week 2, Week 24 and Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

The symptom-specific measure FACIT-F was developed to assess chronic illness therapy with special emphasis on fatigue in the past 7 days. In this study, only the FACIT-F short questionnaire, which is a shorter version of the initial FACIT-F questionnaire, was used. Each of the questions is categorically answered using the scales 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions. The 13 items included in the FACIT-F short can be used to calculate the brief score for FACIT-F scale (score range: 0-52). A positive change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Baseline (n=57)	26.09 Units on a scale Standard Deviation 10.75
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Change at Week 2 (n=57)	2.32 Units on a scale Standard Deviation 9.58
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Change at Week 24 (n=45)	10.53 Units on a scale Standard Deviation 12.06
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Change at Week 52 (n=9)	20.89 Units on a scale Standard Deviation 12.35

SECONDARY outcome

Timeframe: From Baseline to Week 4, Week 24 and Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

The PSQI is a self-rated questionnaire which assesses sleep quality and disturbances over 1-month time interval. Nineteen individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The participant self-rates each of these seven areas of sleep. Scoring of answers is based on a 0 to 3 scale, whereby 3 reflects the negative extreme on the Likert Scale. Global scores range from 0 to 21 and a global sum of "5" or greater indicates a "poor" sleeper. Although there are several questions that request the evaluation of the participant's bed mate or roommate, these are not scored. A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Baseline (n=57)	8.81 Units on a scale Standard Deviation 4.39
Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Change at Week 4 (n=54)	-1.24 Units on a scale Standard Deviation 3.53
Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Change at Week 24 (n=46)	-2.63 Units on a scale Standard Deviation 4.14
Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Change at Week 52 (n=9)	-4.56 Units on a scale Standard Deviation 5.88

SECONDARY outcome

Timeframe: From Baseline to Week 2, Week 24 and Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

The Patient Quality of Sleep VAS assessment represents the participant's assessment of his/her current quality of sleep on a 100 mm horizontal VAS. The extreme left end of the line represents 0="no difficulty to sleep" and the extreme right end 100="extreme sleeping difficulties". A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Change From Baseline in Patient Quality of Sleep VAS Baseline (n=57)	54.95 Units on a scale Standard Deviation 31.23
Change From Baseline in Patient Quality of Sleep VAS Change at Week 2 (n=57)	-8.40 Units on a scale Standard Deviation 23.72
Change From Baseline in Patient Quality of Sleep VAS Change at Week 24 (n=46)	-21.93 Units on a scale Standard Deviation 30.87
Change From Baseline in Patient Quality of Sleep VAS Change at Week 52 (n=9)	-34.22 Units on a scale Standard Deviation 37.03

SECONDARY outcome

Timeframe: From Baseline to Week 4, Week 24 and Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of participants with evaluable data for this outcome measure.

The AIMS-SF is a reduced version of the validated AIMS2 questionnaire. The Short Form has been developed using a comprehensive expert-based approach and supported by psychometric testing. The AIMS-SF is a self-administered questionnaire to measure changes in global health, pain, mobility and social function in adult patients with arthritis and reports scores for physical, symptoms, affect, social and work assessments. Scores range from 0 to 10, higher scores indicating higher impact of arthritis on the assessments. A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Baseline: Physical (n= 49)	3.57 Units on a scale Standard Deviation 1.92
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Change at Week 4: Physical (n= 47)	-0.57 Units on a scale Standard Deviation 1.36
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Change at Week 24: Physical (n=38)	-1.41 Units on a scale Standard Deviation 1.83
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Change at Week 52: Physical (n=3)	-3.62 Units on a scale Standard Deviation 2.23
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Baseline: Symptom (50)	6.33 Units on a scale Standard Deviation 2.59
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Change at Week 4: Symptom (n= 48)	-1.15 Units on a scale Standard Deviation 2.46
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Change at Week 24: Symptom (n=40)	-2.69 Units on a scale Standard Deviation 2.80
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Change at Week 52: Symptom (n=3)	-3.89 Units on a scale Standard Deviation 5.91
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Baseline: Affect (n=50)	5.07 Units on a scale Standard Deviation 2.22
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Change at Week 4: Affect (n= 48)	-0.66 Units on a scale Standard Deviation 1.56
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Change at Week 24: Affect (n=40)	-1.74 Units on a scale Standard Deviation 2.22
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Change at Week 52: Affect (n=3)	-4.50 Units on a scale Standard Deviation 2.22
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Baseline: Social (n=50)	5.36 Units on a scale Standard Deviation 1.73
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Change at Week 4: Social (n= 48)	0.18 Units on a scale Standard Deviation 1.41
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Change at Week 24: Social (n=40)	-0.56 Units on a scale Standard Deviation 1.61
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Change at Week 52: Social (n=3)	-1.46 Units on a scale Standard Deviation 2.37
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Baseline: Work (n=26)	3.17 Units on a scale Standard Deviation 2.46
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Change at Week 4: Work (n= 23)	-0.92 Units on a scale Standard Deviation 2.53
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Change at Week 24: Work (n=21)	-0.65 Units on a scale Standard Deviation 2.87
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) Change at Week 52: Work (n=1)	3.75 Units on a scale Standard Deviation NA Standard deviation is not estimable for 1 participant.

SECONDARY outcome

Timeframe: From Baseline to Week 2, Week 24 and Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

The Patient Fatigue VAS assessment represents the participant's assessment of his/her current level of fatigue on a 100 mm horizontal VAS. The extreme left end of the line represents 0="no fatigue" and the extreme right end 100="extreme fatigue". A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Change From Baseline in Patient Fatigue VAS Baseline (n=57)	60.19 Units on a scale Standard Deviation 24.79
Change From Baseline in Patient Fatigue VAS Change at Week 2 (n=57)	-3.74 Units on a scale Standard Deviation 20.68
Change From Baseline in Patient Fatigue VAS Change at Week 24 (n=46)	-21.48 Units on a scale Standard Deviation 28.07
Change From Baseline in Patient Fatigue VAS Change at Week 52 (n=9)	-50.89 Units on a scale Standard Deviation 26.11

SECONDARY outcome

Timeframe: From Baseline to Week 2, Week 24 and Week 52

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

The Patient Satisfaction VAS assessment represents the participant's assessment of his/her current satisfaction with treatment on a 100 mm horizontal VAS. The extreme left end of the line represents 0="no satisfaction" and the extreme right end 100="extremely satisfied". A positive change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Change From Baseline in Patient Satisfaction VAS Baseline (n=53)	39.66 Units on a scale Standard Deviation 28.63
Change From Baseline in Patient Satisfaction VAS Change at Week 2 (n=53)	9.49 Units on a scale Standard Deviation 33.97
Change From Baseline in Patient Satisfaction VAS Change at Week 24 (n=43)	33.07 Units on a scale Standard Deviation 35.50
Change From Baseline in Patient Satisfaction VAS Change at Week 52 (n=8)	49.38 Units on a scale Standard Deviation 35.12

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

The 23-item RA-WIS is a simple, validated screening tool for work instability, i.e., the consequences of a mismatch between an individual's functional ability and their work tasks. This self-administered questionnaire covers a broad range of specific work-related issues and enables monitoring the risk of work disability in rheumatoid arthritis patients. The RA-WIS is scored by summing responses from all 23 scale items. The scale ranges from 0 to 23. Cut points have been established to differentiate levels of work instability: low < 10, moderate 10-17 and high > 17. A negative change from baseline indicates an improvement.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Change From Baseline in Work Instability Scale for Rheumatoid Arthritis (RA-WIS) Baseline (n=26)	13.15 Units on a scale Standard Deviation 6.05
Change From Baseline in Work Instability Scale for Rheumatoid Arthritis (RA-WIS) Change at Week 24 (n=22)	-3.55 Units on a scale Standard Deviation 6.96

SECONDARY outcome

Timeframe: Week 24

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure.

The abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) derived from the TSQM Version 1.4 but without the five items of the side effects domain, is a reliable and valid measure to assess participants' satisfaction with treatment. The TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain. Domains included are effectiveness, convenience and global satisfaction.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Treatment Satisfaction Questionnaire for Medication (TSQM ) Scores Effectiveness (n=46)	66.7 Units on a scale Standard Deviation 19.07
Treatment Satisfaction Questionnaire for Medication (TSQM ) Scores Convenience (n=46)	76.09 Units on a scale Standard Deviation 15.66
Treatment Satisfaction Questionnaire for Medication (TSQM ) Scores Global Satisfaction (n=46)	65.06 Units on a scale Standard Deviation 15.52

SECONDARY outcome

Timeframe: Up to 52 weeks

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Outcome measures

Measure

Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.

Safety: Percentage of Participants With Adverse Events

96.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: The FAS consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of participants with evaluable data for this outcome measure.

Outcome measures

Measure	Tocilizumab n=57 Participants Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
Safety: Percentage of Participants With Anti-tocilizumab Antibodies Baseline (n= 55)	0 percentage of participants
Safety: Percentage of Participants With Anti-tocilizumab Antibodies Week 24 (n= 43)	1.7 percentage of participants

Adverse Events

Tocilizumab

Serious events: 5 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tocilizumab n=57 participants at risk Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the long term extension (LTE) period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 milligram (mg) tocilizumab was administered subcutaneously once weekly.
Cardiac disorders Atrial Flutter	1.8% 1/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Gastrointestinal disorders Diverticular perforation	1.8% 1/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Immune system disorders Hypersensitivity	1.8% 1/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Infections and infestations Arthritis Infective	1.8% 1/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Injury, poisoning and procedural complications Fall	1.8% 1/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Injury, poisoning and procedural complications Femur Fracture	1.8% 1/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic Lymphocytic Leukaemia	1.8% 1/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.

Other adverse events

Measure	Tocilizumab n=57 participants at risk Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the long term extension (LTE) period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 milligram (mg) tocilizumab was administered subcutaneously once weekly.
Ear and labyrinth disorders Vertigo	7.0% 4/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Gastrointestinal disorders Abdominal pain upper	5.3% 3/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Gastrointestinal disorders Diarrhoea	5.3% 3/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Gastrointestinal disorders Nausea	7.0% 4/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
General disorders Fatigue	7.0% 4/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
General disorders Injection site erythema	5.3% 3/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Infections and infestations Bronchitis	15.8% 9/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Infections and infestations Nasopharyngitis	12.3% 7/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Infections and infestations Urinary tract infection	7.0% 4/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	5.3% 3/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	8.8% 5/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Nervous system disorders Dizziness	5.3% 3/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Nervous system disorders Headache	5.3% 3/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Respiratory, thoracic and mediastinal disorders Cough	12.3% 7/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.3% 3/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Skin and subcutaneous tissue disorders Hyperhidrosis	8.8% 5/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Vascular disorders Hot flush	5.3% 3/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Vascular disorders Hypertension	5.3% 3/57 • Up to 52 weeks The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.

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