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

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02031471
• Collaborator: (none)
• Enrollment: 57
• Locations: 17
• Arm: 1
• Duration (Months): 20
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This open-label, single-arm study will evaluate the efficacy, safety and tolerability of subcutaneously administered tocilizumab in monotherapy and/or in combination with methotrexate and other non-biologic disease modifying anti-rheumatic drug (DMARDs) in participants with active rheumatoid arthritis (RA) who are naïve to tocilizumab. Participants will receive tocilizumab 162 milligram (mg) subcutaneously weekly for 24 weeks. Participants who complete the core study achieving at least a moderate European League Against Rheumatism (EULAR) response at Week 24 may enter the extension phase and receive for a further 28 weeks at the most.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: tocilizumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: TOSCARA: An Open-label, Single Arm Study to Evaluate the Efficacy, Safety and Tolerability of Tocilizumab (TCZ) Subcutaneous in TCZ-naïve Patients With Active Rheumatoid Arthritis
• Study Start Date: Jan 1, 2014
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.

Drug: tocilizumab; Fixed dose of 162 mg subcutaneously weekly; Other Names: RoActemra/Actemra

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score in the Full Analysis Set (FAS) [From baseline to Week 24]

   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.

2. Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score in the Per Protocol Set (PPS) [From baseline to Week 24]

   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.

Secondary Outcome Measures

1. Percentage of Participants With Positive American College of Rheumatology (ACR) Response Scores [From Baseline to Week 2, Week 24, and Week 52]

   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.

2. Percentage of Participants With Responses According to European League Against Rheumatism (EULAR ) Criteria [From Baseline to Week 2, Week 24]

   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.

3. Change From Baseline in Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI) [From Baseline to Week 2, Week 24 and Week 52]

   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.

4. Change in Total Tender/Swollen Joint Counts (TJC/SJC) [From Baseline to Week 2, Week 24 and Week 52]

   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.

5. Percentage of Participants With Corticosteroid Dose Reduction/Discontinuation [Up to Week 52]

6. Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity [Baseline to Week 2, Week 24 and Week 52]

   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.

7. Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity [From Baseline to Week 2, Week 24 and Week 52]

   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.

8. Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity [From Baseline to Week 2, Week 24 and Week 52]

   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.

9. Percentage of Participants Achieving a Clinically Significant Improvement in DAS28 [From Baseline to Week 2, Week 24 and Week 52]

   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.

10. Change From Baseline in Physician's Global Assessment of Disease Activity VAS [From Baseline to Week 2, Week 24 and Week 52]

    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.

11. Change From Baseline in Patient's Global Assessment of Disease Activity VAS [From Baseline to Week 2, Week 24 and Week 52]

    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.

12. Change From Baseline in Patient's Assessment of Pain VAS [From Baseline to Week 2 and Week 24]

    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.

13. Acute Phase Reactants: Change From Baseline in CRP [From Baseline to Week 2, Week 24 and Week 52]

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

14. Acute Phase Reactants: Change From Baseline in ESR [From Baseline to Week 2, Week 24 and Week 52]

    A negative change from baseline in ESR indicates an improvement.

15. Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) [From Baseline to Week 2, Week 24 and Week 52]

    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.

16. Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) [From Baseline to Week 2, Week 24 and Week 52]

    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.

17. Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) [From Baseline to Week 4, Week 24 and Week 52]

    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.

18. Change From Baseline in Patient Quality of Sleep VAS [From Baseline to Week 2, Week 24 and Week 52]

    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.

19. Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) [From Baseline to Week 4, Week 24 and Week 52]

    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.

20. Change From Baseline in Patient Fatigue VAS [From Baseline to Week 2, Week 24 and Week 52]

    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.

21. Change From Baseline in Patient Satisfaction VAS [From Baseline to Week 2, Week 24 and Week 52]

    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.

22. Change From Baseline in Work Instability Scale for Rheumatoid Arthritis (RA-WIS) [From Baseline to Week 24]

    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.

23. Treatment Satisfaction Questionnaire for Medication (TSQM ) Scores [Week 24]

    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.

24. Safety: Percentage of Participants With Adverse Events [Up to 52 weeks]

    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.

25. Safety: Percentage of Participants With Anti-tocilizumab Antibodies [Baseline, Week 24]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult participants, >/= 18 years of age

• Active moderate to severe rheumatoid arthritis according to the revised (1987) American College of Rheumatology (ACR) criteria or EULAR/ACR (2010) criteria

• Inadequate response or intolerant to previous therapy with two or more non-biologic disease-modifying anti-rheumatic drugs (DMARDs), one of which is methotrexate, administered in an optimal way during at least 3 months; eligible participants may also be inadequate responders to a maximum of one biologic DMARD

• Oral corticosteroids (</= 10 milligram per day (mg/day) prednisolone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs; up to the recommended dose) are permitted if on stable dose regimen for >/= 4 weeks prior to baseline

• Permitted DMARDs are allowed if at stable dose for at least 4 weeks prior to baseline

• Receiving treatment on an outpatient basis, not including tocilizumab

• Females of childbearing potential and males with female partners of childbearing potential must agree to use reliable means of contraception as defined by protocol

Exclusion Criteria:

• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline or during long term extension (LTE) period

• Rheumatic autoimmune disease other than rheumatoid arthritis

• Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis

• Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16

• Prior history of or current inflammatory joint disease other than RA

• Exposure to tocilizumab (intravenous or subcutaneous) at any time prior to baseline

• Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening

• Intraarticular or parenteral corticosteroids within 4 weeks prior to baseline

• History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies

• Evidence of serious concomitant disease or disorder

• Known active current or history of recurrent infection

• Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening

• Active Tuberculosis (TB) requiring treatment within the previous 3 years

• Positive for hepatitis B or hepatitis C

• Primary or secondary immunodeficiency (history of or currently active)

• Pregnant or lactating women

• Neuropathies or other conditions that might interfere with pain evaluation

• Inadequate hematologic, renal or liver function

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Aalst		Belgium	9300
2		Assebroek		Belgium	8310
3		Bonheiden		Belgium	2820
4		Bruxelles		Belgium	1020
5		Bruxelles		Belgium	1050
6		Bruxelles		Belgium	1070
7		Genk		Belgium	3600
8		Gent		Belgium	9000
9		Gilly (Charleroi)		Belgium	6000
10		Gosselies		Belgium	6041
11		Haine-Saint-Paul		Belgium	7100
12		Liège		Belgium	4000
13		Roeselare		Belgium	8800
14		Sijsele		Belgium	8340
15		Sint-Niklaas		Belgium	9100
16		Wilrijk		Belgium	2610
17		Luxembourg		Luxembourg	2763

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02031471
• Other Study ID Numbers: ML28701
• First Posted: Jan 9, 2014
• Last Update Posted: Aug 1, 2017
• Last Verified: Jun 1, 2017

• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Period Title: 24 Week Treatment Period
STARTED	57
COMPLETED	46
NOT COMPLETED	11
Period Title: 24 Week Treatment Period
STARTED	39
COMPLETED	37
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Overall Participants	57
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.49 (11.08)
Sex: Female, Male (Count of Participants)
Female	44 77.2%
Male	13 22.8%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score in the Full Analysis Set (FAS)
Description	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.
Time Frame	From baseline to Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline (n=56)	5.55 (1.17)
Change at Week 24 (n=42)	-3.24 (1.47)

2. Primary Outcome

Title	Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score in the Per Protocol Set (PPS)
Description	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.
Time Frame	From baseline to Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline (n= 27)	5.73 (1.33)
Change at Week 24 (n= 20)	-3.21 (1.42)

3. Secondary Outcome

Title	Percentage of Participants With Positive American College of Rheumatology (ACR) Response Scores
Description	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.
Time Frame	From Baseline to Week 2, Week 24, and Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline: ACR 20 (n=55)	0 0%
Week 2: ACR 20 (n=51)	21.6 37.9%
Week 24: ACR 20 (n=39)	84.6 148.4%
Week 52: ACR 20 (n=8)	100 175.4%
Baseline: ACR 50 (n=55)	0 0%
Week 2: ACR 50 (n=52)	1.9 3.3%
Week 24: ACR 50 (n=39)	66.7 117%
Week 52: ACR 50 (n=8)	62.5 109.6%
Baseline: ACR 70 (n=55)	0 0%
Week 2: ACR 70 (n=52)	0 0%
Week 24: ACR 70 (n=39)	38.5 67.5%
Week 52: ACR 70 (n=8)	25.0 43.9%

4. Secondary Outcome

Title	Percentage of Participants With Responses According to European League Against Rheumatism (EULAR ) Criteria
Description	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.
Time Frame	From Baseline to Week 2, Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Week 2: Good response (n=56)	17.9 31.4%
Week 24: Good response (n=42)	76.2 133.7%
Week 2: Moderate response (n=56)	50.0 87.7%
Week 24: Moderate response (n=42)	19.0 33.3%
Week 2: No response (n=56)	32.1 56.3%
Week 24: No response (n=42)	4.8 8.4%

5. Secondary Outcome

Title	Change From Baseline in Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI)
Description	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.
Time Frame	From Baseline to Week 2, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline (n=53)	33.26 (13.50)
Change at Week 2: SDAI (n=52)	-9.00 (11.89)
Change at Week 24: SDAI (n=38)	-25.33 (13.63)
Change at Week 52: SDAI (n=7)	-34.04 (16.01)
Baseline: CDAI (n= 55)	31.86 (12.60)
Change at Week 2: CDAI (n=55)	-7.61 (11.51)
Change at Week 24: CDAI (n=42)	-23.55 (13.03)
Change at Week 52: CDAI (n=8)	-29.99 (13.89)

6. Secondary Outcome

Title	Change in Total Tender/Swollen Joint Counts (TJC/SJC)
Description	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.
Time Frame	From Baseline to Week 2, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline: TJC (n=53)	16.02 (11.77)
Change at Week 2: TJC (n=53)	-3.58 (8.91)
Change at Week 24: TJC (n=41)	-12.10 (11.07)
Change at Week 52: TJC (n=8)	-17.25 (13.02)
Baseline: SJC (n=55)	10.20 (7.14)
Change at Week 2: SJC (n=55)	-3.93 (7.33)
Change at Week 24: SJC (n=42)	-9.81 (7.84)
Change at Week 52: SJC (n=8)	-11.75 (7.76)

7. Secondary Outcome

Title	Percentage of Participants With Corticosteroid Dose Reduction/Discontinuation
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	26
Number [percentage of participants]	50.0 87.7%

8. Secondary Outcome

Title	Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity
Description	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.
Time Frame	Baseline to Week 2, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline: Clinical remission (n=55)	0 0%
Week 2: Clinical remission (n=56)	1.8 3.2%
Week 24: Clinical remission (n=43)	30.2 53%
Week 52: Clinical remission (n=8)	37.5 65.8%
Baseline: Low disease activity (n=55)	0 0%
Week 2: Low disease activity (n=56)	7.1 12.5%
Week 24: Low disease activity (n=43)	34.9 61.2%
Week 52: Low disease activity (n=8)	25.0 43.9%
Baseline: Moderate disease activity (n=55)	21.8 38.2%
Week 2: Moderate disease activity (n=56)	48.2 84.6%
Week 24: Moderate disease activity (n=43)	30.2 53%
Week 52: Moderate disease activity (n=8)	37.5 65.8%
Baseline: High disease activity (n=55)	78.2 137.2%
Week 2: High disease activity (n=56)	42.9 75.3%
Week 24: High disease activity (n=43)	4.7 8.2%
Week 52: High disease activity (n=8)	0 0%

9. Secondary Outcome

Title	Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity
Description	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.
Time Frame	From Baseline to Week 2, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline: Clinical remission (n=53)	0 0%
Week 2: Clinical remission (n=55)	1.8 3.2%
Week 24: Clinical remission (n=40)	30.0 52.6%
Week 52: Clinical remission (n=7)	42.9 75.3%
Baseline: Low disease activity (n=53)	0 0%
Week 2: Low disease activity (n=55)	7.3 12.8%
Week 24: Low disease activity (n=40)	40.0 70.2%
Week 52: Low disease activity (n=7)	14.3 25.1%
Baseline: Moderate disease activity (n=53)	30.2 53%
Week 2: Moderate disease activity (n=55)	54.5 95.6%
Week 24: Moderate disease activity (n=40)	25.0 43.9%
Week 52: Moderate disease activity (n=7)	42.9 75.3%
Baseline: High disease activity (n=53)	69.8 122.5%
Week 2: High disease activity (n=55)	36.4 63.9%
Week 24: High disease activity (n=40)	5.0 8.8%
Week 52: High disease activity (n=7)	0 0%

10. Secondary Outcome

Title	Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity
Description	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.
Time Frame	From Baseline to Week 2, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline: Clinical remission (n=56)	0 0%
Week 2: Clinical remission (n=56)	7.1 12.5%
Week 24: Clinical remission (n=42)	64.3 112.8%
Week 52: Clinical remission (n=8)	87.5 153.5%
Baseline: Low disease activity (n=56)	1.8 3.2%
Week 2: Low disease activity (n=56)	16.1 28.2%
Week 24: Low disease activity (n=42)	16.7 29.3%
Week 52: Low disease activity (n=8)	0 0%
Baseline: Moderate disease activity (n=56)	35.7 62.6%
Week 2: Moderate disease activity (n=56)	53.6 94%
Week 24: Moderate disease activity (n=42)	19.0 33.3%
Week 52: Moderate disease activity (n=8)	12.5 21.9%
Baseline: High disease activity (n=56)	62.5 109.6%
Week 2: High disease activity (n=56)	23.2 40.7%
Week 24: High disease activity (n=42)	0 0%
Week 52: High disease activity (n=8)	0 0%

11. Secondary Outcome

Title	Percentage of Participants Achieving a Clinically Significant Improvement in DAS28
Description	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.
Time Frame	From Baseline to Week 2, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Week 2 (n=56)	66.1 116%
Week 24 (n=42)	90.5 158.8%
Week 52 (n=8)	100 175.4%

12. Secondary Outcome

Title	Change From Baseline in Physician's Global Assessment of Disease Activity VAS
Description	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.
Time Frame	From Baseline to Week 2, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline (n=56)	64.93 (17.73)
Change at Week 2 (n=56)	-16.34 (16.88)
Change at Week 24 (n=45)	-48.93 (25.06)
Change at Week 52 (n=9)	-57.44 (23.26)

13. Secondary Outcome

Title	Change From Baseline in Patient's Global Assessment of Disease Activity VAS
Description	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.
Time Frame	From Baseline to Week 2, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline (n=57)	67.28 (22.25)
Change at Week 2 (n=57)	-11.82 (23.23)
Change at Week 24 (n=46)	-36.02 (29.38)
Change at Week 52 (n=9)	-44.78 (35.87)

14. Secondary Outcome

Title	Change From Baseline in Patient's Assessment of Pain VAS
Description	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.
Time Frame	From Baseline to Week 2 and Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline (n=57)	66.77 (21.43)
Change at Week 2 (n=57)	-11.32 (19.74)
Change at Week 24 (n=46)	-35.37 (27.03)
Change at Week 52 (n=9)	-49.33 (39.58)

15. Secondary Outcome

Title	Acute Phase Reactants: Change From Baseline in CRP
Description	A negative change from baseline in CRP level indicates an improvement.
Time Frame	From Baseline to Week 2, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline (n=55)	13.79 (20.78)
Change at Week 2 (n=54)	-13.19 (20.64)
Change at Week 24 (n=42)	-10.12 (14.50)
Change at Week 52 (n=8)	-25.07 (23.03)

16. Secondary Outcome

Title	Acute Phase Reactants: Change From Baseline in ESR
Description	A negative change from baseline in ESR indicates an improvement.
Time Frame	From Baseline to Week 2, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline (n=56)	33.75 (28.90)
Change at Week 2 (n=55)	-19.95 (18.22)
Change at Week 24 (n=44)	-22.80 (24.88)
Change at Week 52 (n=9)	-27.78 (23.82)

17. Secondary Outcome

Title	Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)
Description	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.
Time Frame	From Baseline to Week 2, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline (n=57)	1.44 (0.68)
Change at Week 2 (n=57)	-0.08 (0.43)
Change at Week 24 (n=46)	-0.54 (0.68)
Change at Week 52 (n=9)	-1.33 (0.68)

18. Secondary Outcome

Title	Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
Description	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.
Time Frame	From Baseline to Week 2, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline (n=57)	26.09 (10.75)
Change at Week 2 (n=57)	2.32 (9.58)
Change at Week 24 (n=45)	10.53 (12.06)
Change at Week 52 (n=9)	20.89 (12.35)

19. Secondary Outcome

Title	Change From Baseline in Pittsburgh Sleep Quality Index (PSQI)
Description	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.
Time Frame	From Baseline to Week 4, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline (n=57)	8.81 (4.39)
Change at Week 4 (n=54)	-1.24 (3.53)
Change at Week 24 (n=46)	-2.63 (4.14)
Change at Week 52 (n=9)	-4.56 (5.88)

20. Secondary Outcome

Title	Change From Baseline in Patient Quality of Sleep VAS
Description	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.
Time Frame	From Baseline to Week 2, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline (n=57)	54.95 (31.23)
Change at Week 2 (n=57)	-8.40 (23.72)
Change at Week 24 (n=46)	-21.93 (30.87)
Change at Week 52 (n=9)	-34.22 (37.03)

21. Secondary Outcome

Title	Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF)
Description	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.
Time Frame	From Baseline to Week 4, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline: Physical (n= 49)	3.57 (1.92)
Change at Week 4: Physical (n= 47)	-0.57 (1.36)
Change at Week 24: Physical (n=38)	-1.41 (1.83)
Change at Week 52: Physical (n=3)	-3.62 (2.23)
Baseline: Symptom (50)	6.33 (2.59)
Change at Week 4: Symptom (n= 48)	-1.15 (2.46)
Change at Week 24: Symptom (n=40)	-2.69 (2.80)
Change at Week 52: Symptom (n=3)	-3.89 (5.91)
Baseline: Affect (n=50)	5.07 (2.22)
Change at Week 4: Affect (n= 48)	-0.66 (1.56)
Change at Week 24: Affect (n=40)	-1.74 (2.22)
Change at Week 52: Affect (n=3)	-4.50 (2.22)
Baseline: Social (n=50)	5.36 (1.73)
Change at Week 4: Social (n= 48)	0.18 (1.41)
Change at Week 24: Social (n=40)	-0.56 (1.61)
Change at Week 52: Social (n=3)	-1.46 (2.37)
Baseline: Work (n=26)	3.17 (2.46)
Change at Week 4: Work (n= 23)	-0.92 (2.53)
Change at Week 24: Work (n=21)	-0.65 (2.87)
Change at Week 52: Work (n=1)	3.75 (NA)

22. Secondary Outcome

Title	Change From Baseline in Patient Fatigue VAS
Description	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.
Time Frame	From Baseline to Week 2, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline (n=57)	60.19 (24.79)
Change at Week 2 (n=57)	-3.74 (20.68)
Change at Week 24 (n=46)	-21.48 (28.07)
Change at Week 52 (n=9)	-50.89 (26.11)

23. Secondary Outcome

Title	Change From Baseline in Patient Satisfaction VAS
Description	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.
Time Frame	From Baseline to Week 2, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline (n=53)	39.66 (28.63)
Change at Week 2 (n=53)	9.49 (33.97)
Change at Week 24 (n=43)	33.07 (35.50)
Change at Week 52 (n=8)	49.38 (35.12)

24. Secondary Outcome

Title	Change From Baseline in Work Instability Scale for Rheumatoid Arthritis (RA-WIS)
Description	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.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline (n=26)	13.15 (6.05)
Change at Week 24 (n=22)	-3.55 (6.96)

25. Secondary Outcome

Title	Treatment Satisfaction Questionnaire for Medication (TSQM ) Scores
Description	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.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Effectiveness (n=46)	66.7 (19.07)
Convenience (n=46)	76.09 (15.66)
Global Satisfaction (n=46)	65.06 (15.52)

26. Secondary Outcome

Title	Safety: Percentage of Participants With Adverse Events
Description	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.
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Number [percentage of participants]	96.5 169.3%

27. Secondary Outcome

Title	Safety: Percentage of Participants With Anti-tocilizumab Antibodies
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tocilizumab
Arm/Group Description	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.
Measure Participants	57
Baseline (n= 55)	0 0%
Week 24 (n= 43)	1.7 3%

Adverse Events

Time Frame	Up to 52 weeks
Adverse Event Reporting Description	The safety population consisted of all participants included in the study who received at least one dose of subcutaneous tocilizumab.
Arm/Group Title	Tocilizumab
Arm/Group Description	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.
All Cause Mortality
	Tocilizumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Tocilizumab
	Affected / at Risk (%)	# Events
Total	5/57 (8.8%)
Cardiac disorders
Atrial Flutter	1/57 (1.8%)
Gastrointestinal disorders
Diverticular perforation	1/57 (1.8%)
Immune system disorders
Hypersensitivity	1/57 (1.8%)
Infections and infestations
Arthritis Infective	1/57 (1.8%)
Injury, poisoning and procedural complications
Fall	1/57 (1.8%)
Femur Fracture	1/57 (1.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic Lymphocytic Leukaemia	1/57 (1.8%)
Other (Not Including Serious) Adverse Events
	Tocilizumab
	Affected / at Risk (%)	# Events
Total	36/57 (63.2%)
Ear and labyrinth disorders
Vertigo	4/57 (7%)
Gastrointestinal disorders
Abdominal pain upper	3/57 (5.3%)
Diarrhoea	3/57 (5.3%)
Nausea	4/57 (7%)
General disorders
Fatigue	4/57 (7%)
Injection site erythema	3/57 (5.3%)
Infections and infestations
Bronchitis	9/57 (15.8%)
Nasopharyngitis	7/57 (12.3%)
Urinary tract infection	4/57 (7%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	3/57 (5.3%)
Rheumatoid arthritis	5/57 (8.8%)
Nervous system disorders
Dizziness	3/57 (5.3%)
Headache	3/57 (5.3%)
Respiratory, thoracic and mediastinal disorders
Cough	7/57 (12.3%)
Oropharyngeal pain	3/57 (5.3%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	5/57 (8.8%)
Vascular disorders
Hot flush	3/57 (5.3%)
Hypertension	3/57 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.